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Sample records for affect multiple steps

  1. Mutations in the CRE pocket of bacterial RNA polymerase affect multiple steps of transcription

    PubMed Central

    Petushkov, Ivan; Pupov, Danil; Bass, Irina; Kulbachinskiy, Andrey

    2015-01-01

    During transcription, the catalytic core of RNA polymerase (RNAP) must interact with the DNA template with low-sequence specificity to ensure efficient enzyme translocation and RNA extension. Unexpectedly, recent structural studies of bacterial promoter complexes revealed specific interactions between the nontemplate DNA strand at the downstream edge of the transcription bubble (CRE, core recognition element) and a protein pocket formed by core RNAP (CRE pocket). We investigated the roles of these interactions in transcription by analyzing point amino acid substitutions and deletions in Escherichia coli RNAP. The mutations affected multiple steps of transcription, including promoter recognition, RNA elongation and termination. In particular, we showed that interactions of the CRE pocket with a nontemplate guanine immediately downstream of the active center stimulate RNA-hairpin-dependent transcription pausing but not other types of pausing. Thus, conformational changes of the elongation complex induced by nascent RNA can modulate CRE effects on transcription. The results highlight the roles of specific core RNAP–DNA interactions at different steps of RNA synthesis and suggest their importance for transcription regulation in various organisms. PMID:25990734

  2. A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation.

    PubMed

    Ruehle, Marisa D; Zhang, Haibo; Sheridan, Ryan M; Mitra, Somdeb; Chen, Yuanwei; Gonzalez, Ruben L; Cooperman, Barry S; Kieft, Jeffrey S

    2015-01-01

    Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs. PMID:26523395

  3. A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation

    PubMed Central

    Ruehle, Marisa D; Zhang, Haibo; Sheridan, Ryan M; Mitra, Somdeb; Chen, Yuanwei; Gonzalez, Ruben L; Cooperman, Barry S; Kieft, Jeffrey S

    2015-01-01

    Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs. DOI: http://dx.doi.org/10.7554/eLife.08146.001 PMID:26523395

  4. The Cystic Fibrosis-causing Mutation ΔF508 Affects Multiple Steps in Cystic Fibrosis Transmembrane Conductance Regulator Biogenesis*

    PubMed Central

    Thibodeau, Patrick H.; Richardson, John M.; Wang, Wei; Millen, Linda; Watson, Jarod; Mendoza, Juan L.; Du, Kai; Fischman, Sharon; Senderowitz, Hanoch; Lukacs, Gergely L.; Kirk, Kevin; Thomas, Philip J.

    2010-01-01

    The deletion of phenylalanine 508 in the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator is directly associated with >90% of cystic fibrosis cases. This mutant protein fails to traffic out of the endoplasmic reticulum and is subsequently degraded by the proteasome. The effects of this mutation may be partially reversed by the application of exogenous osmolytes, expression at low temperature, and the introduction of second site suppressor mutations. However, the specific steps of folding and assembly of full-length cystic fibrosis transmembrane conductance regulator (CFTR) directly altered by the disease-causing mutation are unclear. To elucidate the effects of the ΔF508 mutation, on various steps in CFTR folding, a series of misfolding and suppressor mutations in the nucleotide binding and transmembrane domains were evaluated for effects on the folding and maturation of the protein. The results indicate that the isolated NBD1 responds to both the ΔF508 mutation and intradomain suppressors of this mutation. In addition, identification of a novel second site suppressor of the defect within the second transmembrane domain suggests that ΔF508 also effects interdomain interactions critical for later steps in the biosynthesis of CFTR. PMID:20667826

  5. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  6. A mechanism of oxygen sensing in yeast. Multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity.

    PubMed

    Hon, Thomas; Dodd, Athena; Dirmeier, Reinhard; Gorman, Nadia; Sinclair, Peter R; Zhang, Li; Poyton, Robert O

    2003-12-12

    Heme plays central roles in oxygen sensing and utilization in many living organisms. In yeast, heme mediates the effect of oxygen on the expression of many genes involved in using or detoxifying oxygen. However, a direct link between intracellular heme level and oxygen concentration has not been vigorously established. In this report, we have examined the relationships among oxygen levels, heme levels, Hap1 activity, and HAP1 expression. We found that Hap1 activity is controlled in vivo by heme and not by its precursors and that heme activates Hap1 even in anoxic cells. We also found that Hap1 activity exhibits the same oxygen dose-response curves as Hap1-dependent aerobic genes and that these dose-response curves have a sharp break at approximately 1 microM O2. The results show that the intracellular signaling heme level, reflected as Hap1 activity, is closely correlated with oxygen concentration. Furthermore, we found that bypass of all heme synthetic steps but ferrochelatase by deuteroporphyrin IX does not circumvent the need for oxygen in Hap1 full activation by heme, suggesting that the last step of heme synthesis, catalyzed by ferrochelatase, is also subjected to oxygen control. Our results show that multiple heme synthetic steps can sense oxygen concentration and provide significant insights into the mechanism of oxygen sensing in yeast. PMID:14512429

  7. Three Steps to Mastering Multiplication Facts

    ERIC Educational Resources Information Center

    Kling, Gina; Bay-Williams, Jennifer M.

    2015-01-01

    "That was the day I decided I was bad at math." Countless times, preservice and in-service teachers make statements such as this after sharing vivid memories of learning multiplication facts. Timed tests; public competitive games, such as Around the World; and visible displays of who has and has not mastered groups of facts still…

  8. Small RAB GTPases Regulate Multiple Steps of Mitosis.

    PubMed

    Miserey-Lenkei, Stéphanie; Colombo, María I

    2016-01-01

    GTPases of the RAB family are key regulators of multiple steps of membrane trafficking. Several members of the RAB GTPase family have been implicated in mitotic progression. In this review, we will first focus on the function of endosome-associated RAB GTPases reported in early steps of mitosis, spindle pole maturation, and during cytokinesis. Second, we will discuss the role of Golgi-associated RAB GTPases at the metaphase/anaphase transition and during cytokinesis. PMID:26925400

  9. Small RAB GTPases Regulate Multiple Steps of Mitosis

    PubMed Central

    Miserey-Lenkei, Stéphanie; Colombo, María I.

    2016-01-01

    GTPases of the RAB family are key regulators of multiple steps of membrane trafficking. Several members of the RAB GTPase family have been implicated in mitotic progression. In this review, we will first focus on the function of endosome-associated RAB GTPases reported in early steps of mitosis, spindle pole maturation, and during cytokinesis. Second, we will discuss the role of Golgi-associated RAB GTPases at the metaphase/anaphase transition and during cytokinesis. PMID:26925400

  10. Arousal and exposure duration affect forward step initiation.

    PubMed

    Bouman, Daniëlle; Stins, John F; Beek, Peter J

    2015-01-01

    Emotion influences parameters of goal-directed whole-body movements in several ways. For instance, previous research has shown that approaching (moving toward) pleasant stimuli is easier compared to approaching unpleasant stimuli. However, some studies found that when emotional pictures are viewed for a longer time, approaching unpleasant stimuli may in fact be facilitated. The effect of viewing duration may have modulated whole-body approach movement in previous research but this has not been investigated to date. In the current study, participants initiated a step forward after viewing neutral, high-arousal pleasant and high-arousal unpleasant stimuli. The viewing duration of the stimuli was set to seven different durations, varying from 100 to 4000 ms. Valence and arousal scores were collected for all stimuli. The results indicate that both viewing duration and the arousal of the stimuli influence kinematic parameters in forward gait initiation. Specifically, longer viewing duration, compared to shorter viewing duration, (a) diminished the step length and peak velocity in both neutral and emotional stimuli, (b) increased reaction time in neutral stimuli and, (c) decreased reaction time in pleasant and unpleasant stimuli. Strikingly, no differences were found between high-arousal pleasant and high-arousal unpleasant stimuli. In other words, the valence of the stimuli did not influence kinematic parameters of forward step initiation. Instead the arousal level (neutral: low; pleasant and unpleasant: high) explained the variance found in the results. The kinematics of forward gait initiation seemed to be reflected in the subjective arousal scores, but not the valence scores. So it seems arousal affects forward gait initiation parameters more strongly than valence. In addition, longer viewing duration seemed to cause diminished alertness, affecting GI parameters. These results shed new light on the prevailing theoretical interpretations regarding approach motivation

  11. Arousal and exposure duration affect forward step initiation

    PubMed Central

    Bouman, Daniëlle; Stins, John F.; Beek, Peter J.

    2015-01-01

    Emotion influences parameters of goal-directed whole-body movements in several ways. For instance, previous research has shown that approaching (moving toward) pleasant stimuli is easier compared to approaching unpleasant stimuli. However, some studies found that when emotional pictures are viewed for a longer time, approaching unpleasant stimuli may in fact be facilitated. The effect of viewing duration may have modulated whole-body approach movement in previous research but this has not been investigated to date. In the current study, participants initiated a step forward after viewing neutral, high-arousal pleasant and high-arousal unpleasant stimuli. The viewing duration of the stimuli was set to seven different durations, varying from 100 to 4000 ms. Valence and arousal scores were collected for all stimuli. The results indicate that both viewing duration and the arousal of the stimuli influence kinematic parameters in forward gait initiation. Specifically, longer viewing duration, compared to shorter viewing duration, (a) diminished the step length and peak velocity in both neutral and emotional stimuli, (b) increased reaction time in neutral stimuli and, (c) decreased reaction time in pleasant and unpleasant stimuli. Strikingly, no differences were found between high-arousal pleasant and high-arousal unpleasant stimuli. In other words, the valence of the stimuli did not influence kinematic parameters of forward step initiation. Instead the arousal level (neutral: low; pleasant and unpleasant: high) explained the variance found in the results. The kinematics of forward gait initiation seemed to be reflected in the subjective arousal scores, but not the valence scores. So it seems arousal affects forward gait initiation parameters more strongly than valence. In addition, longer viewing duration seemed to cause diminished alertness, affecting GI parameters. These results shed new light on the prevailing theoretical interpretations regarding approach motivation

  12. How Interactions Affect Multiple Kinesin Dynamics

    NASA Astrophysics Data System (ADS)

    Kolomeisky, Anatoly

    2013-03-01

    Intracellullar transport is supported by several classes of enzymatic molecules known as motor proteins. Cellular cargos are frequently transported by teams of motor proteins, and recent experimental and theoretical studies uncovered many features of such complex dynamics. Here we investigate theoretically the role of nonmechanical interactions between kinesin motor proteins and microtubules in the collective motion of motor proteins. Our analysis is based on stochastic model that explicitly takes into account all chemical and mechanical transitions. Nonmechanical interactions are assumed to affect kinesin mechanochemistry only when the motors are separated by less than 3 microtubule lattice sites, and it is shown that relatively weak interaction energies can have a significant effect on collective motor dynamics. In agreement with optical trapping experiments on structurally defined kinesin complexes, the model predicts that these effects primarily occur when cargos are transported against loads exceeding single-kinesin stalling forces. These results highlights the complex dynamics of multiple motor proteins in cellular transport phenomena.

  13. Multiple time step integrators in ab initio molecular dynamics

    SciTech Connect

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

  14. PSEUDOBULBAR AFFECT IN MULTIPLE SCLEROSIS PATIENTS.

    PubMed

    Vidović, Viktor; Rovazdi, Merisanda Časar; Kraml, Oto; Kes, Vanja Bašić

    2015-06-01

    The aim of the study was to determine the prevalence of pseudobulbar affect (PBA) in patients with multiple sclerosis (MS) and to analyze the link between PBA and patient age, sex, clinical course of MS, disease duration and degree of disability. The study was conducted on 79 MS patients that underwent inpatient rehabilitation at the Lipik Special Hospital for Medical Rehabilitation in the period from August 15, 2014 to February 15, 2015. PBA is a term used for an emotional disinhibition syndrome characterized by sudden and involuntary episodes of crying or laughing which are not in proportion to the stimulus applied or occur without stimulus. The condition can be present in patients with various neurological disorders, such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, patients having recovered from stroke, or following traumatic brain injury. The estimated prevalence in patients with MS ranges from 10% to 46.2%. As a measuring instrument in the study, we used the Center for Neurologic Study-Lability Scale (CNS-LS), where a sum 17 denoted positive finding. The total number of respondents was 79, of which 33 (41.8%) met the CNS-LS criteria for the diagnosis of PBA. There was no statistically significant correlation between PBA, age and degree of disability, although PBA was more common in women and in patients with a secondary progressive form of the disease. We found that 42.4% of respondents with positive CNS-LS criteria for PBA did not inform their neurologist on the presence of sudden mood changes. The high frequency of PBA and the fact that a significant proportion of patients did not inform the neurologist on their affective disturbances call for an active approach to diagnosis and treatment. PMID:26415311

  15. Multiple Sclerosis Affects Skeletal Muscle Characteristics

    PubMed Central

    Wens, Inez; Dalgas, Ulrik; Vandenabeele, Frank; Krekels, Maartje; Grevendonk, Lotte; Eijnde, Bert O.

    2014-01-01

    Background The impact of multiple sclerosis (MS) on skeletal muscle characteristics, such as muscle fiber cross sectional area (CSA), fiber type proportion, muscle strength and whole muscle mass, remains conflicting. Methods In this cross sectional study, body composition and muscle strength of the quadriceps were assessed in 34 MS (EDSS: 2.5±0.19) patients and 18 matched healthy controls (HC). Hereafter a muscle biopsy (m.vastus lateralis) was taken. Results Compared to HC, mean muscle fiber CSA of all fibers, as well as CSA of type I, II and IIa fibers were smaller and muscle strength of the quadriceps was lower in MS patients. Whole body composition was comparable between groups. However, compared to HC, the biopsied leg tended to have a higher fat percentage (p = 0.1) and a lower lean mass (p = 0.06) in MS patients. Conclusion MS seems to negatively influence skeletal muscle fiber CSA, muscle strength and muscle mass of the lower limbs of mildly affected MS patients. This emphasises the need for rehabilitation programs focusing on muscle preservation of the lower limb. Trial Registration ClinicalTrials.gov NCT01845896 PMID:25264868

  16. A Stochastic, Resonance-Free Multiple Time-Step Algorithm for Polarizable Models That Permits Very Large Time Steps.

    PubMed

    Margul, Daniel T; Tuckerman, Mark E

    2016-05-10

    Molecular dynamics remains one of the most widely used computational tools in the theoretical molecular sciences to sample an equilibrium ensemble distribution and/or to study the dynamical properties of a system. The efficiency of a molecular dynamics calculation is limited by the size of the time step that can be employed, which is dictated by the highest frequencies in the system. However, many properties of interest are connected to low-frequency, long time-scale phenomena, requiring many small time steps to capture. This ubiquitous problem can be ameliorated by employing multiple time-step algorithms, which assign different time steps to forces acting on different time scales. In such a scheme, fast forces are evaluated more frequently than slow forces, and as the former are often computationally much cheaper to evaluate, the savings can be significant. Standard multiple time-step approaches are limited, however, by resonance phenomena, wherein motion on the fastest time scales limits the step sizes that can be chosen for the slower time scales. In atomistic models of biomolecular systems, for example, the largest time step is typically limited to around 5 fs. Previously, we introduced an isokinetic extended phase-space algorithm (Minary et al. Phys. Rev. Lett. 2004, 93, 150201) and its stochastic analog (Leimkuhler et al. Mol. Phys. 2013, 111, 3579) that eliminate resonance phenomena through a set of kinetic energy constraints. In simulations of a fixed-charge flexible model of liquid water, for example, the time step that could be assigned to the slow forces approached 100 fs. In this paper, we develop a stochastic isokinetic algorithm for multiple time-step molecular dynamics calculations using a polarizable model based on fluctuating dipoles. The scheme developed here employs two sets of induced dipole moments, specifically, those associated with short-range interactions and those associated with a full set of interactions. The scheme is demonstrated on

  17. Multiple-time-stepping generalized hybrid Monte Carlo methods

    NASA Astrophysics Data System (ADS)

    Escribano, Bruno; Akhmatskaya, Elena; Reich, Sebastian; Azpiroz, Jon M.

    2015-01-01

    Performance of the generalized shadow hybrid Monte Carlo (GSHMC) method [1], which proved to be superior in sampling efficiency over its predecessors [2-4], molecular dynamics and hybrid Monte Carlo, can be further improved by combining it with multi-time-stepping (MTS) and mollification of slow forces. We demonstrate that the comparatively simple modifications of the method not only lead to better performance of GSHMC itself but also allow for beating the best performed methods, which use the similar force splitting schemes. In addition we show that the same ideas can be successfully applied to the conventional generalized hybrid Monte Carlo method (GHMC). The resulting methods, MTS-GHMC and MTS-GSHMC, provide accurate reproduction of thermodynamic and dynamical properties, exact temperature control during simulation and computational robustness and efficiency. MTS-GHMC uses a generalized momentum update to achieve weak stochastic stabilization to the molecular dynamics (MD) integrator. MTS-GSHMC adds the use of a shadow (modified) Hamiltonian to filter the MD trajectories in the HMC scheme. We introduce a new shadow Hamiltonian formulation adapted to force-splitting methods. The use of such Hamiltonians improves the acceptance rate of trajectories and has a strong impact on the sampling efficiency of the method. Both methods were implemented in the open-source MD package ProtoMol and were tested on a water and a protein systems. Results were compared to those obtained using a Langevin Molly (LM) method [5] on the same systems. The test results demonstrate the superiority of the new methods over LM in terms of stability, accuracy and sampling efficiency. This suggests that putting the MTS approach in the framework of hybrid Monte Carlo and using the natural stochasticity offered by the generalized hybrid Monte Carlo lead to improving stability of MTS and allow for achieving larger step sizes in the simulation of complex systems.

  18. Multiple-time-stepping generalized hybrid Monte Carlo methods

    SciTech Connect

    Escribano, Bruno; Akhmatskaya, Elena; Reich, Sebastian; Azpiroz, Jon M.

    2015-01-01

    Performance of the generalized shadow hybrid Monte Carlo (GSHMC) method [1], which proved to be superior in sampling efficiency over its predecessors [2–4], molecular dynamics and hybrid Monte Carlo, can be further improved by combining it with multi-time-stepping (MTS) and mollification of slow forces. We demonstrate that the comparatively simple modifications of the method not only lead to better performance of GSHMC itself but also allow for beating the best performed methods, which use the similar force splitting schemes. In addition we show that the same ideas can be successfully applied to the conventional generalized hybrid Monte Carlo method (GHMC). The resulting methods, MTS-GHMC and MTS-GSHMC, provide accurate reproduction of thermodynamic and dynamical properties, exact temperature control during simulation and computational robustness and efficiency. MTS-GHMC uses a generalized momentum update to achieve weak stochastic stabilization to the molecular dynamics (MD) integrator. MTS-GSHMC adds the use of a shadow (modified) Hamiltonian to filter the MD trajectories in the HMC scheme. We introduce a new shadow Hamiltonian formulation adapted to force-splitting methods. The use of such Hamiltonians improves the acceptance rate of trajectories and has a strong impact on the sampling efficiency of the method. Both methods were implemented in the open-source MD package ProtoMol and were tested on a water and a protein systems. Results were compared to those obtained using a Langevin Molly (LM) method [5] on the same systems. The test results demonstrate the superiority of the new methods over LM in terms of stability, accuracy and sampling efficiency. This suggests that putting the MTS approach in the framework of hybrid Monte Carlo and using the natural stochasticity offered by the generalized hybrid Monte Carlo lead to improving stability of MTS and allow for achieving larger step sizes in the simulation of complex systems.

  19. GRB-081029: A Step Towards Understanding Multiple Afterglow Components

    NASA Technical Reports Server (NTRS)

    Holland Stephen T.

    2010-01-01

    We present an analysis of the unusual optical light curve of the gamma-ray burst-081029 at a redshift of z = 3.8474. We combine X-ray and optical observations from (Swift) with optical and infrared data from REM to obtain a detailed data set extending from approx 10(exp 2)s to approx 10(exp 5)s after the BAT trigger, and from approx.10 keV to 16,000 AA. The X-ray afterglow showed a shallow initial decay followed by u rapid decay after about 18,000 s. The optical afterglow, however, shows an uncharecteristic rise at about 5000 s that has no corresponding feature in the X-ray light curve. The data are not consistent with a single-component jet. It is possible that there are multiple physical components contributing to the afterglow of GRB-081029.

  20. Accuracy of StepWatch™ and ActiGraph Accelerometers for Measuring Steps Taken among Persons with Multiple Sclerosis

    PubMed Central

    Sandroff, Brian M.; Motl, Robert W.; Pilutti, Lara A.; Learmonth, Yvonne C.; Ensari, Ipek; Dlugonski, Deirdre; Klaren, Rachel E.; Balantrapu, Swathi; Riskin, Barry J.

    2014-01-01

    Introduction There has been increased interest in the objective monitoring of free-living walking behavior using accelerometers in clinical research involving persons with multiple sclerosis (MS). The current investigation examined and compared the accuracy of the StepWatch activity monitor and ActiGraph model GT3X+ accelerometer for capturing steps taken during various speeds of prolonged, over-ground ambulation in persons with MS who had mild, moderate, and severe disability. Methods Sixty-three persons with MS underwent a neurological examination for generation of an EDSS score and undertook two trials of walking on the GAITRite electronic walkway. Participants were fitted with accelerometers, and undertook three modified six-minute walk (6MW) tests that were interspersed with 10–15 minutes of rest. The first 6MW was undertaken at a comfortable walking speed (CWS), and the two remaining 6MW tests were undertaken above (faster walking speed; FWS) or below (slower walking speed; SWS) the participant's CWS. The actual number of steps taken was counted through direct observation using hand-tally counters. Results The StepWatch activity monitor (99.8%–99.9%) and ActiGraph model GT3X+ accelerometer (95.6%–97.4%) both demonstrated highly accurate measurement of steps taken under CWS and FWS conditions. The StepWatch had better accuracy (99.0%) than the ActiGraph (95.5%) in the overall sample under the SWS condition, and this was particularly apparent in those with severe disability (StepWatch: 95.7%; ActiGraph: 87.3%). The inaccuracy in measurement for the ActiGraph was associated with alterations of gait (e.g., slower gait velocity, shorter step length, wider base of support). Conclusions This research will help inform the choice of accelerometer to be adopted in clinical trials of MS wherein the monitoring of free-living walking behavior is of particular value. PMID:24714028

  1. Comparing Multiple Discrepancies Theory to Affective Models of Subjective Wellbeing

    ERIC Educational Resources Information Center

    Blore, Jed D.; Stokes, Mark A.; Mellor, David; Firth, Lucy; Cummins, Robert A.

    2011-01-01

    The Subjective Wellbeing (SWB) literature is replete with competing theories detailing the mechanisms underlying the construction and maintenance of SWB. The current study aimed to compare and contrast two of these approaches: multiple discrepancies theory (MDT) and an affective-cognitive theory of SWB. MDT posits SWB to be the result of perceived…

  2. Range and Velocity Estimation of Moving Targets Using Multiple Stepped-frequency Pulse Trains

    PubMed Central

    Li, Gang; Meng, Huadong; Xia, Xiang-Gen; Peng, Ying-Ning

    2008-01-01

    Range and velocity estimation of moving targets using conventional stepped-frequency pulse radar may suffer from the range-Doppler coupling and the phase wrapping. To overcome these problems, this paper presents a new radar waveform named multiple stepped-frequency pulse trains and proposes a new algorithm. It is shown that by using multiple stepped-frequency pulse trains and the robust phase unwrapping theorem (RPUT), both of the range-Doppler coupling and the phase wrapping can be robustly resolved, and accordingly, the range and the velocity of a moving target can be accurately estimated.

  3. PIC Algorithm with Multiple Poisson Equation Solves During One Time Step

    NASA Astrophysics Data System (ADS)

    Ren, Junxue; Godar, Trenton; Menart, James; Mahalingam, Sudhakar; Choi, Yongjun; Loverich, John; Stoltz, Peter H.

    2015-09-01

    In order to reduce the overall computational time of a PIC (particle-in-cell) computer simulation, an attempt was made to utilize larger time step sizes by implementing multiple solutions of Poisson's equation within one time step. The hope was this would make the PIC simulation stable at larger time steps than an explicit technique can use, and using larger time steps would reduce the overall computational time, even though the computational time per time step would increase. A three-dimensional PIC code that tracks electrons and ions throughout a three-dimensional Cartesian computational domain is used to perform this study. The results of altering the number of times Poisson's equation is solved during a single time step are presented. Also, the size of the time that can be used and still maintain a stable solution is surveyed. The results indicate that using multiple Poisson solves during one time step provides some ability to use larger time steps in PIC simulations, but the increase in time step size is not significant and the overall simulation run time is not reduced

  4. Steps/day ability to predict anthropometric changes is not affected by its plausibility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We evaluated whether treating steps/day data for implausible values (30,000) affected the ability of these data to predict intervention-induced anthropometric (waist circumference, body mass index, percent body fat, and fat mass) changes. Data were from 269 African American participants wh...

  5. Steps/day ability to predict anthropometric changes is not affected by its plausibility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We evaluated whether treating steps/day data for implausible values (<500 or >30,000) affected the ability of these data to predict intervention-induced anthropometric (waist circumference, body mass index, percent body fat, and fat mass) changes. Data were from 269 African American participants wh...

  6. Clinical Importance of Steps Taken per Day among Persons with Multiple Sclerosis

    PubMed Central

    Motl, Robert W.; Pilutti, Lara A.; Learmonth, Yvonne C.; Goldman, Myla D.; Brown, Ted

    2013-01-01

    Background The number of steps taken per day (steps/day) provides a reliable and valid outcome of free-living walking behavior in persons with multiple sclerosis (MS). Objective This study examined the clinical meaningfulness of steps/day using the minimal clinically important difference (MCID) value across stages representing the developing impact of MS. Methods This study was a secondary analysis of de-identified data from 15 investigations totaling 786 persons with MS and 157 healthy controls. All participants provided demographic information and wore an accelerometer or pedometer during the waking hours of a 7-day period. Those with MS further provided real-life, health, and clinical information and completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and Patient Determined Disease Steps (PDDS) scale. MCID estimates were based on regression analyses and analysis of variance for between group differences. Results The mean MCID from self-report scales that capture subtle changes in ambulation (1-point change in PDSS scores and 10-point change in MSWS-12 scores) was 779 steps/day (14% of mean score for MS sample); the mean MCID for clinical/health outcomes (MS type, duration, weight status) was 1,455 steps/day (26% of mean score for MS sample); real-life anchors (unemployment, divorce, assistive device use) resulted in a mean MCID of 2,580 steps/day (45% of mean score for MS sample); and the MCID for the cumulative impact of MS (MS vs. control) was 2,747 steps/day (48% of mean score for MS sample). Conclusion The change in motion sensor output of ∼800 steps/day appears to represent a lower-bound estimate of clinically meaningful change in free-living walking behavior in interventions of MS. PMID:24023843

  7. Step-up procedures for non-inferiority tests with multiple experimental treatments.

    PubMed

    Kwong, Koon Shing; Cheung, Siu Hung; Hayter, Anthony J

    2016-08-01

    Non-inferiority (NI) trials are becoming more popular. The NI of a new treatment compared with a standard treatment is established when the new treatment maintains a substantial fraction of the treatment effect of the standard treatment. A valid NI trial is also required to show assay sensitivity, the demonstration of the standard treatment having the expected effect with a size comparable to those reported in previous placebo-controlled studies. A three-arm NI trial is a clinical study that includes a new treatment, a standard treatment and a placebo. Most of the statistical methods developed for three-arm NI trials are designed for the existence of only one new treatment. Recently, a single-step procedure was developed to deal with NI trials with multiple new treatments with the overall familywise error rate controlled at a specified level. In this article, we extend the single-step procedure to two new step-up procedures for NI trials with multiple new treatments. A comparative study of test power shows that both proposed step-up procedures provide a significant improvement of power when compared to the single-step procedure. One of the two proposed step-up procedures also allows the flexibility of allocating different error rates between the sensitivity hypothesis and the NI hypotheses so that the assignment of fewer patients to the placebo becomes possible when designing NI trials. We illustrate the new procedures using data from a clinical trial. PMID:23531623

  8. Nocturnal melatonin secretion in multiple sclerosis patients with affective disorders.

    PubMed

    Sandyk, R; Awerbuch, G I

    1993-02-01

    The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS), a chronic demyelinating disease of CNS. Since nocturnal melatonin secretion is low in some groups of patients with mental depression, we predicted lower melatonin secretion in MS patients with history of affective illness compared to those without psychiatric disorders. To test this hypothesis, we studied single nocturnal plasma melatonin levels and the incidence of pineal calcification (PC) on CT scan in a cohort of 25 MS patients (4 men, 21 women; mean age = 39.4 years, SD = 9.3), 15 of whom had a history of coexisting psychiatric disorders with predominant affective symptomatology. Other factors that may be related to depression such as vitamin B12, folic acid, zinc, magnesium, and homocysteine, were also included in the analysis. Neither any of the metabolic factors surveyed nor the incidence of PC distinguished the psychiatric from the control group. However, the mean melatonin level in the psychiatric patients was significantly lower than in the control group. Since low melatonin secretion in patients with depression may be related to a phase-advance of the circadian oscillator regulating the offset of melatonin secretion, we propose that the depression of MS likewise may reflect the presence of dampened circadian oscillators. Furthermore, since exacerbation of motor symptoms in MS patients may be temporally related to worsening of depression, we propose that circadian phase lability may also underlie the relapsing-remitting course of the disease. Consequently, pharmacological agents such as lithium or bright light therapy, which have been shown to phase-delay circadian rhythms, might be effective in the treatment of affective symptoms in MS as well as preventing motor exacerbation and hastening a remission from an acute attack. PMID:8063528

  9. Consistency of internal fluxes in a hydrological model running at multiple time steps

    NASA Astrophysics Data System (ADS)

    Ficchi, Andrea; Perrin, Charles; Andréassian, Vazken

    2016-04-01

    Improving hydrological models remains a difficult task and many ways can be explored, among which one can find the improvement of spatial representation, the search for more robust parametrization, the better formulation of some processes or the modification of model structures by trial-and-error procedure. Several past works indicate that model parameters and structure can be dependent on the modelling time step, and there is thus some rationale in investigating how a model behaves across various modelling time steps, to find solutions for improvements. Here we analyse the impact of data time step on the consistency of the internal fluxes of a rainfall-runoff model run at various time steps, by using a large data set of 240 catchments. To this end, fine time step hydro-climatic information at sub-hourly resolution is used as input of a parsimonious rainfall-runoff model (GR) that is run at eight different model time steps (from 6 minutes to one day). The initial structure of the tested model (i.e. the baseline) corresponds to the daily model GR4J (Perrin et al., 2003), adapted to be run at variable sub-daily time steps. The modelled fluxes considered are interception, actual evapotranspiration and intercatchment groundwater flows. Observations of these fluxes are not available, but the comparison of modelled fluxes at multiple time steps gives additional information for model identification. The joint analysis of flow simulation performance and consistency of internal fluxes at different time steps provides guidance to the identification of the model components that should be improved. Our analysis indicates that the baseline model structure is to be modified at sub-daily time steps to warrant the consistency and realism of the modelled fluxes. For the baseline model improvement, particular attention is devoted to the interception model component, whose output flux showed the strongest sensitivity to modelling time step. The dependency of the optimal model

  10. Multiple Time-Step Dual-Hamiltonian Hybrid Molecular Dynamics - Monte Carlo Canonical Propagation Algorithm.

    PubMed

    Chen, Yunjie; Kale, Seyit; Weare, Jonathan; Dinner, Aaron R; Roux, Benoît

    2016-04-12

    A multiple time-step integrator based on a dual Hamiltonian and a hybrid method combining molecular dynamics (MD) and Monte Carlo (MC) is proposed to sample systems in the canonical ensemble. The Dual Hamiltonian Multiple Time-Step (DHMTS) algorithm is based on two similar Hamiltonians: a computationally expensive one that serves as a reference and a computationally inexpensive one to which the workload is shifted. The central assumption is that the difference between the two Hamiltonians is slowly varying. Earlier work has shown that such dual Hamiltonian multiple time-step schemes effectively precondition nonlinear differential equations for dynamics by reformulating them into a recursive root finding problem that can be solved by propagating a correction term through an internal loop, analogous to RESPA. Of special interest in the present context, a hybrid MD-MC version of the DHMTS algorithm is introduced to enforce detailed balance via a Metropolis acceptance criterion and ensure consistency with the Boltzmann distribution. The Metropolis criterion suppresses the discretization errors normally associated with the propagation according to the computationally inexpensive Hamiltonian, treating the discretization error as an external work. Illustrative tests are carried out to demonstrate the effectiveness of the method. PMID:26918826

  11. Multiple Time-Step Dual-Hamiltonian Hybrid Molecular Dynamics — Monte Carlo Canonical Propagation Algorithm

    PubMed Central

    Weare, Jonathan; Dinner, Aaron R.; Roux, Benoît

    2016-01-01

    A multiple time-step integrator based on a dual Hamiltonian and a hybrid method combining molecular dynamics (MD) and Monte Carlo (MC) is proposed to sample systems in the canonical ensemble. The Dual Hamiltonian Multiple Time-Step (DHMTS) algorithm is based on two similar Hamiltonians: a computationally expensive one that serves as a reference and a computationally inexpensive one to which the workload is shifted. The central assumption is that the difference between the two Hamiltonians is slowly varying. Earlier work has shown that such dual Hamiltonian multiple time-step schemes effectively precondition nonlinear differential equations for dynamics by reformulating them into a recursive root finding problem that can be solved by propagating a correction term through an internal loop, analogous to RESPA. Of special interest in the present context, a hybrid MD-MC version of the DHMTS algorithm is introduced to enforce detailed balance via a Metropolis acceptance criterion and ensure consistency with the Boltzmann distribution. The Metropolis criterion suppresses the discretization errors normally associated with the propagation according to the computationally inexpensive Hamiltonian, treating the discretization error as an external work. Illustrative tests are carried out to demonstrate the effectiveness of the method. PMID:26918826

  12. A multiple time stepping algorithm for efficient multiscale modeling of platelets flowing in blood plasma

    NASA Astrophysics Data System (ADS)

    Zhang, Peng; Zhang, Na; Deng, Yuefan; Bluestein, Danny

    2015-03-01

    We developed a multiple time-stepping (MTS) algorithm for multiscale modeling of the dynamics of platelets flowing in viscous blood plasma. This MTS algorithm improves considerably the computational efficiency without significant loss of accuracy. This study of the dynamic properties of flowing platelets employs a combination of the dissipative particle dynamics (DPD) and the coarse-grained molecular dynamics (CGMD) methods to describe the dynamic microstructures of deformable platelets in response to extracellular flow-induced stresses. The disparate spatial scales between the two methods are handled by a hybrid force field interface. However, the disparity in temporal scales between the DPD and CGMD that requires time stepping at microseconds and nanoseconds respectively, represents a computational challenge that may become prohibitive. Classical MTS algorithms manage to improve computing efficiency by multi-stepping within DPD or CGMD for up to one order of magnitude of scale differential. In order to handle 3-4 orders of magnitude disparity in the temporal scales between DPD and CGMD, we introduce a new MTS scheme hybridizing DPD and CGMD by utilizing four different time stepping sizes. We advance the fluid system at the largest time step, the fluid-platelet interface at a middle timestep size, and the nonbonded and bonded potentials of the platelet structural system at two smallest timestep sizes. Additionally, we introduce parameters to study the relationship of accuracy versus computational complexities. The numerical experiments demonstrated 3000x reduction in computing time over standard MTS methods for solving the multiscale model. This MTS algorithm establishes a computationally feasible approach for solving a particle-based system at multiple scales for performing efficient multiscale simulations.

  13. A Multiple Time Stepping Algorithm for Efficient Multiscale Modeling of Platelets Flowing in Blood Plasma

    PubMed Central

    Zhang, Peng; Zhang, Na; Deng, Yuefan; Bluestein, Danny

    2015-01-01

    We developed a multiple time-stepping (MTS) algorithm for multiscale modeling of the dynamics of platelets flowing in viscous blood plasma. This MTS algorithm improves considerably the computational efficiency without significant loss of accuracy. This study of the dynamic properties of flowing platelets employs a combination of the dissipative particle dynamics (DPD) and the coarse-grained molecular dynamics (CGMD) methods to describe the dynamic microstructures of deformable platelets in response to extracellular flow-induced stresses. The disparate spatial scales between the two methods are handled by a hybrid force field interface. However, the disparity in temporal scales between the DPD and CGMD that requires time stepping at microseconds and nanoseconds respectively, represents a computational challenge that may become prohibitive. Classical MTS algorithms manage to improve computing efficiency by multi-stepping within DPD or CGMD for up to one order of magnitude of scale differential. In order to handle 3–4 orders of magnitude disparity in the temporal scales between DPD and CGMD, we introduce a new MTS scheme hybridizing DPD and CGMD by utilizing four different time stepping sizes. We advance the fluid system at the largest time step, the fluid-platelet interface at a middle timestep size, and the nonbonded and bonded potentials of the platelet structural system at two smallest timestep sizes. Additionally, we introduce parameters to study the relationship of accuracy versus computational complexities. The numerical experiments demonstrated 3000x reduction in computing time over standard MTS methods for solving the multiscale model. This MTS algorithm establishes a computationally feasible approach for solving a particle-based system at multiple scales for performing efficient multiscale simulations. PMID:25641983

  14. Hydrologic consistency analysed through modeling at multiple time steps: does hydrological model performance benefit from finer time step information?

    NASA Astrophysics Data System (ADS)

    Ficchi, Andrea; Perrin, Charles; Andréassian, Vazken

    2015-04-01

    We investigate the operational utility of fine time step hydro-climatic information using a large catchment data set. The originality of this data set lies in the availability of precipitation data from the 6-minute rain gauges of Météo-France, and in the size of the catchment set (217 French catchments in total). The rainfall-runoff model used (GR4) has been adapted to hourly and sub-hourly time steps (up to 6-minute) from the daily time step version (Perrin et al., 2003). The model is applied at different time steps ranging from 6-minute to 1 day (6-, 12-, 30-minute, 1-, 3-, 6-, 12-hour and 1 day) and the evolution of model performance for each catchment is evaluated at the daily time step by aggregation of model outputs. Three classes of behavior are found according to the trend of model performance as the time step becomes finer: (i) catchments presenting an improvement of model performance; (ii) catchments with a model performance insensitive to the time step; (iii) catchments for which the performance even deteriorates as the time step becomes finer. The reasons behind these different trends are investigated from a hydrological point of view, by relating the model sensitivity to data at finer time step to catchment descriptors. References: Perrin, C., C. Michel and V. Andréassian (2003), "Improvement of a parsimonious model for streamflow simulation", Journal of Hydrology, 279(1-4): 275-289.

  15. Multiple-step triangular-pattern phase shifting and the influence of number of steps and pitch on measurement accuracy

    SciTech Connect

    Jia Peirong; Kofman, Jonathan; English, Chad

    2007-06-01

    We present new extensions of the two-step, triangular-pattern phase-shifting method for different numbers of phase-shifting steps to increase measurement accuracy and to analyze the influence of the number of phase-shifting steps and pitch of the projected triangular intensity-profile pattern on the measurement accuracy. Phase-shifting algorithms to generate the intensity ratio, essential for surface reconstruction, were developed for each measurement method. Experiments determined that higher measurement accuracy can be obtained with a greater number of phase-shifting steps and a lower value of pitch, as long as the pitch is appropriately selected to be divisible by the number of phase-shifting steps and not below an optimal value, where intensity-ratio unwrapping failure would occur.

  16. A simple procedure eliminating multiple optimization steps required in developing multiplex PCR reactions

    SciTech Connect

    Grondin, V.; Roskey, M.; Klinger, K.; Shuber, T.

    1994-09-01

    The PCR technique is one of the most powerful tools in modern molecular genetics and has achieved widespread use in the analysis of genetic diseases. Typically, a region of interest is amplified from genomic DNA or cDNA and examined by various methods of analysis for mutations or polymorphisms. In cases of small genes and transcripts, amplification of single, small regions of DNA are sufficient for analysis. However, when analyzing large genes and transcripts, multiple PCRs may be required to identify the specific mutation or polymorphism of interest. Ever since it has been shown that PCR could simultaneously amplify multiple loci in the human dystrophin gene, multiplex PCR has been established as a general technique. The properities of multiplex PCR make it a useful tool and preferable to simultaneous uniplex PCR in many instances. However, the steps for developing a multiplex PCR can be laborious, with significant difficulty in achieving equimolar amounts of several different amplicons. We have developed a simple method of primer design that has enabled us to eliminate a number of the standard optimization steps required in developing a multiplex PCR. Sequence-specific oligonucleotide pairs were synthesized for the simultaneous amplification of multiple exons within the CFTR gene. A common non-complementary 20 nucleotide sequence was attached to each primer, thus creating a mixture of primer pairs all containing a universal primer sequence. Multiplex PCR reactions were carried out containing target DNA, a mixture of several chimeric primer pairs and primers complementary to only the universal portion of the chimeric primers. Following optimization of conditions for the universal primer, limited optimization was needed for successful multiplex PCR. In contrast, significant optimization of the PCR conditions were needed when pairs of sequence specific primers were used together without the universal sequence.

  17. How the interplay between mechanical and non-mechanical interactions affects multiple kinesin dynamics

    PubMed Central

    Uppulury, Karthik; Efremov, Artem K.; Driver, Jonathan W.; Jamison, D. Kenneth; Diehl, Michael R.; Kolomeisky, Anatoly B.

    2012-01-01

    Intracellular transport is supported by enzymes called motor proteins that are often coupled to the same cargo and function collectively. Recent experiments and theoretical advances have been able to explain certain behaviors of multiple motor systems by elucidating how unequal load sharing between coupled motors changes how they bind, step, and detach. However, non-mechanical interactions are typically overlooked despite several studies suggesting that microtubule-bound kinesins interact locally via short-range non-mechanical potentials. This work develops a new stochastic model to explore how these types of interactions influence multiple kinesin functions in addition to mechanical coupling. Non-mechanical interactions are assumed to affect kinesin mechanochemistry only when the motors are separated by less than three microtubule lattice sites, and it is shown that relatively weak interaction energies (~2 kBT) can have an appreciable influence over collective motor velocities and detachment rates. In agreement with optical trapping experiments on structurally-defined kinesin complexes, the model predicts that these effects primarily occur when cargos are transported against loads exceeding single-kinesin stalling forces. Overall, these results highlight the inter-dependent nature of factors influencing collective motor functions, namely, that the way the bound configuration of a multiple motor system evolves under load determines how local non-mechanical interactions influence motor cooperation. PMID:22724436

  18. One-step integration of multiple genes into the oleaginous yeast Yarrowia lipolytica.

    PubMed

    Gao, Shuliang; Han, Linna; Zhu, Li; Ge, Mei; Yang, Sheng; Jiang, Yu; Chen, Daijie

    2014-12-01

    Yarrowia lipolytica is an unconventional yeast, and is generally recognized as safe (GRAS). It provides a versatile fermentation platform that is used commercially to produce many added-value products. Here we report a multiple fragment assembly method that allows one-step integration of an entire β-carotene biosynthesis pathway (~11 kb, consisting of four genes) via in vivo homologous recombination into the rDNA locus of the Y. lipolytica chromosome. The highest efficiency was 21%, and the highest production of β-carotene was 2.2 ± 0.3 mg per g dry cell weight. The total procedure was completed in less than one week, as compared to a previously reported sequential gene integration method that required n weeks for n genes. This time-saving method will facilitate synthetic biology, metabolic engineering and functional genomics studies of Y. lipolytica. PMID:25216641

  19. Visualization of shock-wave formation processes during shock reflection at obstacles with multiple steps

    NASA Astrophysics Data System (ADS)

    Kobayashi, Susumu; Adachi, Takashi

    According to standard textbooks on compressible fluid dynamics, a shock wave is formed by an accumulation of compression waves. However, the process by which an accumulated compression wave grows into a shock wave has never been visualized. In the present paper, the authors tried to visualize this process using a model wedge with multiple steps. This model is useful for generating a series of compression waves and can simulate a compression process that occurs in a shock tube. By estimating the triple-point trajectory angle, we demonstrated visually that an accumulated compression wave grows into a shock wave. Further reflection experiments over a rough-surface wedge confirmed the tendency for the triple point trajectory angle χ to reach the asymptotic value χs in the end.

  20. Multiple ``time step'' Monte Carlo simulations: Application to charged systems with Ewald summation

    NASA Astrophysics Data System (ADS)

    Bernacki, Katarzyna; Hetényi, Balázs; Berne, B. J.

    2004-07-01

    Recently, we have proposed an efficient scheme for Monte Carlo simulations, the multiple "time step" Monte Carlo (MTS-MC) [J. Chem. Phys. 117, 8203 (2002)] based on the separation of the potential interactions into two additive parts. In this paper, the structural and thermodynamic properties of the simple point charge water model combined with the Ewald sum are compared for the MTS-MC real-/reciprocal-space split of the Ewald summation and the common Metropolis Monte Carlo method. We report a number of observables as a function of CPU time calculated using MC and MTS-MC. The correlation functions indicate that speedups on the order of 4.5-7.5 can be obtained for systems of 108-500 waters for n=10 splitting parameter.

  1. Yap1 Regulates Multiple Steps of Chondrocyte Differentiation during Skeletal Development and Bone Repair.

    PubMed

    Deng, Yujie; Wu, Ailing; Li, Pikshan; Li, Gang; Qin, Ling; Song, Hai; Mak, Kinglun Kingston

    2016-03-01

    Hippo signaling controls organ size and tissue regeneration in many organs, but its roles in chondrocyte differentiation and bone repair remain elusive. Here, we demonstrate that Yap1, an effector of Hippo pathway inhibits skeletal development, postnatal growth, and bone repair. We show that Yap1 regulates chondrocyte differentiation at multiple steps in which it promotes early chondrocyte proliferation but inhibits subsequent chondrocyte maturation both in vitro and in vivo. Mechanistically, we find that Yap1 requires Teads binding for direct regulation of Sox6 expression to promote chondrocyte proliferation. In contrast, Yap1 inhibits chondrocyte maturation by suppression of Col10a1 expression through interaction with Runx2. In addition, Yap1 also governs the initiation of fracture repair by inhibition of cartilaginous callus tissue formation. Taken together, our work provides insights into the mechanism by which Yap1 regulates endochondral ossification, which may help the development of therapeutic treatment for bone regeneration. PMID:26923596

  2. The multiple time step r-RESPA procedure and polarizable potentials based on induced dipole moments

    NASA Astrophysics Data System (ADS)

    Masella, Michel

    In the present study, we present an accelerating scheme based on the reversible multiple time step r-RESPA method to be used in molecular dynamics simulations with polarizable potentials based on induced dipole moments. Even if the induced dipoles are estimated with an iterative self-consistent procedure, this scheme significantly reduces the CPU time needed to perform a molecular dynamics simulation, up to a factor 2, as compared to the Car-Parrinello method where additional dynamical variables are introduced for the treatment of the induced dipoles. The tests show that stable and reliable molecular dynamics trajectories can be generated with that scheme, and that the physical properties derived from the trajectories are equivalent to those computed with the classical all atom iterative approach and the Car-Parrinello one.

  3. Step wise, multiple objective calibration of a hydrologic model for a snowmelt dominated basin

    USGS Publications Warehouse

    Hay, L.E.; Leavesley, G.H.; Clark, M.P.; Markstrom, S.L.; Viger, R.J.; Umemoto, M.

    2006-01-01

    The ability to apply a hydrologic model to large numbers of basins for forecasting purposes requires a quick and effective calibration strategy. This paper presents a step wise, multiple objective, automated procedure for hydrologic model calibration. This procedure includes the sequential calibration of a model's simulation of solar radiation (SR), potential evapotranspiration (PET), water balance, and daily runoff. The procedure uses the Shuffled Complex Evolution global search algorithm to calibrate the U.S. Geological Survey's Precipitation Runoff Modeling System in the Yampa River basin of Colorado. This process assures that intermediate states of the model (SR and PET on a monthly mean basis), as well as the water balance and components of the daily hydrograph are simulated, consistently with measured values.

  4. Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis

    PubMed Central

    2013-01-01

    Background The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. Methods 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days. Results There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 &ρ = .647, respectively) and Cerebellar (ρ = .501 &ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 &ρ = .805, respectively), MSWS-12 scores (ρ = .801 &ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 &ρ = -.717, respectively). Conclusion This study provides novel evidence supporting the PDDS as valid PRO of disability in MS. PMID:23617555

  5. Artemisinin derivatives inhibit Toxoplasma gondii in vitro at multiple steps in the lytic cycle

    PubMed Central

    D'Angelo, John G.; Bordón, Claudia; Posner, Gary H.; Yolken, Robert; Jones-Brando, Lorraine

    2009-01-01

    Objectives We sought to improve upon the usefulness of artemisinins as anti-Toxoplasma agents by synthesizing new unsaturated, carba derivatives and then testing them for in vitro efficacy against three steps of the lytic cycle of Toxoplasma gondii tachyzoites. Methods Novel derivatives of ART were synthesized and then tested for in vitro antiparasitic activity using T. gondii tachyzoites constitutively expressing β-galactosidase and human fibroblast host cells. Compounds were evaluated for parasite growth inhibition and cytotoxicity, inhibition of replication and inhibition of parasite invasion of host cells. Results Five of the seven new derivatives, 3a–c, 3e and 3f, effectively inhibited T. gondii growth (IC50 = 1.0–4.4 µM); however, only three of these proved to be relatively non-cytotoxic (TD50 ≥ 200 µM). The same five derivatives also inhibited tachyzoite replication, and attachment to and invasion of host cells as effectively as or better than the parent compound ART. In addition, one of the derivatives incapable of inhibiting growth, deoxy-3a, was found to inhibit parasite invasion. Conclusions These new artemisinin derivatives have the ability to inhibit multiple steps of T. gondii's lytic cycle. Synthetic unsaturated, carba derivatives of ART have potential as therapeutic agents for the prevention and treatment of toxoplasmosis in humans. PMID:18988681

  6. Formulation of an explicit-multiple-time-step time integration method for use in a global primitive equation grid model

    NASA Technical Reports Server (NTRS)

    Chao, W. C.

    1982-01-01

    With appropriate modifications, a recently proposed explicit-multiple-time-step scheme (EMTSS) is incorporated into the UCLA model. In this scheme, the linearized terms in the governing equations that generate the gravity waves are split into different vertical modes. Each mode is integrated with an optimal time step, and at periodic intervals these modes are recombined. The other terms are integrated with a time step dictated by the CFL condition for low-frequency waves. This large time step requires a special modification of the advective terms in the polar region to maintain stability. Test runs for 72 h show that EMTSS is a stable, efficient and accurate scheme.

  7. How multiple mating by females affects sexual selection

    PubMed Central

    Shuster, Stephen M.; Briggs, William R.; Dennis, Patricia A.

    2013-01-01

    Multiple mating by females is widely thought to encourage post-mating sexual selection and enhance female fitness. We show that whether polyandrous mating has these effects depends on two conditions. Condition 1 is the pattern of sperm utilization by females; specifically, whether, among females, male mating number, m (i.e. the number of times a male mates with one or more females) covaries with male offspring number, o. Polyandrous mating enhances sexual selection only when males who are successful at multiple mating also sire most or all of each of their mates' offspring, i.e. only when Cov♂(m,o), is positive. Condition 2 is the pattern of female reproductive life-history; specifically, whether female mating number, m, covaries with female offspring number, o. Only semelparity does not erode sexual selection, whereas iteroparity (i.e. when Cov♀(m,o), is positive) always increases the variance in offspring numbers among females, which always decreases the intensity of sexual selection on males. To document the covariance between mating number and offspring number for each sex, it is necessary to assign progeny to all parents, as well as identify mating and non-mating individuals. To document significant fitness gains by females through iteroparity, it is necessary to determine the relative magnitudes of male as well as female contributions to the total variance in relative fitness. We show how such data can be collected, how often they are collected, and we explain the circumstances in which selection favouring multiple mating by females can be strong or weak. PMID:23339237

  8. Multiple Post-translational Modifications Affect Heterologous Protein Synthesis*

    PubMed Central

    Tokmakov, Alexander A.; Kurotani, Atsushi; Takagi, Tetsuo; Toyama, Mitsutoshi; Shirouzu, Mikako; Fukami, Yasuo; Yokoyama, Shigeyuki

    2012-01-01

    Post-translational modifications (PTMs) are required for proper folding of many proteins. The low capacity for PTMs hinders the production of heterologous proteins in the widely used prokaryotic systems of protein synthesis. Until now, a systematic and comprehensive study concerning the specific effects of individual PTMs on heterologous protein synthesis has not been presented. To address this issue, we expressed 1488 human proteins and their domains in a bacterial cell-free system, and we examined the correlation of the expression yields with the presence of multiple PTM sites bioinformatically predicted in these proteins. This approach revealed a number of previously unknown statistically significant correlations. Prediction of some PTMs, such as myristoylation, glycosylation, palmitoylation, and disulfide bond formation, was found to significantly worsen protein amenability to soluble expression. The presence of other PTMs, such as aspartyl hydroxylation, C-terminal amidation, and Tyr sulfation, did not correlate with the yield of heterologous protein expression. Surprisingly, the predicted presence of several PTMs, such as phosphorylation, ubiquitination, SUMOylation, and prenylation, was associated with the increased production of properly folded soluble proteins. The plausible rationales for the existence of the observed correlations are presented. Our findings suggest that identification of potential PTMs in polypeptide sequences can be of practical use for predicting expression success and optimizing heterologous protein synthesis. In sum, this study provides the most compelling evidence so far for the role of multiple PTMs in the stability and solubility of heterologously expressed recombinant proteins. PMID:22674579

  9. Multiple Weather Factors Affect Apparent Survival of European Passerine Birds

    PubMed Central

    Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  10. Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves.

    PubMed

    Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J; Jockenhoevel, Stefan; Mela, Petra

    2015-08-01

    Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels. PMID:25654448

  11. A two-step semiparametric method to accommodate sampling weights in multiple imputation.

    PubMed

    Zhou, Hanzhi; Elliott, Michael R; Raghunathan, Trviellore E

    2016-03-01

    Multiple imputation (MI) is a well-established method to handle item-nonresponse in sample surveys. Survey data obtained from complex sampling designs often involve features that include unequal probability of selection. MI requires imputation to be congenial, that is, for the imputations to come from a Bayesian predictive distribution and for the observed and complete data estimator to equal the posterior mean given the observed or complete data, and similarly for the observed and complete variance estimator to equal the posterior variance given the observed or complete data; more colloquially, the analyst and imputer make similar modeling assumptions. Yet multiply imputed data sets from complex sample designs with unequal sampling weights are typically imputed under simple random sampling assumptions and then analyzed using methods that account for the sampling weights. This is a setting in which the analyst assumes more than the imputer, which can led to biased estimates and anti-conservative inference. Less commonly used alternatives such as including case weights as predictors in the imputation model typically require interaction terms for more complex estimators such as regression coefficients, and can be vulnerable to model misspecification and difficult to implement. We develop a simple two-step MI framework that accounts for sampling weights using a weighted finite population Bayesian bootstrap method to validly impute the whole population (including item nonresponse) from the observed data. In the second step, having generated posterior predictive distributions of the entire population, we use standard IID imputation to handle the item nonresponse. Simulation results show that the proposed method has good frequentist properties and is robust to model misspecification compared to alternative approaches. We apply the proposed method to accommodate missing data in the Behavioral Risk Factor Surveillance System when estimating means and parameters of

  12. Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves

    PubMed Central

    Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J.

    2015-01-01

    Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels. PMID:25654448

  13. Bisphenol A affects androgen receptor function via multiple mechanisms

    PubMed Central

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B. Alex; Jetten, Anton M.; Austin, Christopher, P.; Tice, Raymond R.

    2013-01-01

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. PMID:23562765

  14. Bisphenol A affects androgen receptor function via multiple mechanisms.

    PubMed

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. PMID:23562765

  15. Resource distributions affect social learning on multiple timescales.

    PubMed

    van der Post, Daniel J; Ursem, Bas; Hogeweg, Paulien

    2009-09-01

    We study how learning is shaped by foraging opportunities and self-organizing processes and how this impacts on the effects of "copying what neighbors eat" on multiple timescales. We use an individual-based model with a rich environment, where group foragers learn what to eat. We vary foraging opportunities by changing local variation in resources, studying copying in environments with pure patches, varied patches, and uniform distributed resources. We find that copying can help individuals explore the environment by sharing information, but this depends on how foraging opportunities shape the learning process. Copying has the greatest impact in varied patches, where local resource variation makes learning difficult, but local resource abundance makes copying easy. In contrast, copying is redundant or excessive in pure patches where learning is easy, and mostly ineffective in uniform environments where learning is difficult. Our results reveal that the mediation of copying behavior by individual experience is crucial for the impact of copying. Moreover, we find that the dynamics of social learning at short timescales shapes cultural phenomena. In fact, the integration of learning on short and long timescales generates cumulative cultural improvement in diet. Our results therefore provide insight into how and when such processes can arise. These insights need to be taken into account when considering behavioral patterns in nature. PMID:19701483

  16. Understanding walking activity in multiple sclerosis: step count, walking intensity and uninterrupted walking activity duration related to degree of disability.

    PubMed

    Neven, An; Vanderstraeten, Annelien; Janssens, Davy; Wets, Geert; Feys, Peter

    2016-09-01

    In multiple sclerosis (MS), physical activity (PA) is most commonly measured as number of steps, while also walking intensity and walking activity duration are keys for a healthy lifestyle. The aim of this study was to investigate (1) the number of steps persons with MS (PwMS) take; (2) the number of steps they take at low and moderate intensity; and (3) their walking activity duration for 2, 3, 6, 10, 12 and 14 uninterrupted minutes; all related to the degree of disability. 64 PwMS participated, distinguished in a mild (n = 31) and moderate MS subgroup (n = 34) based on their ambulatory dysfunction (Disease Steps). Standardized clinical tests were performed, and step data from the StepWatch Activity Monitor were collected for seven consecutive days. The results showed that (1) step count in PwMS was lower than PA recommendations, and is negatively influenced by a higher disability degree. (2) No walking was registered during 77 % of the day. PwMS are making steps for 22 % at low and only 1 % at moderate intensity. (3) Both MS subgroups rarely walk for more than six uninterrupted minutes, especially not at moderate intensity. PwMS need to be encouraged to make steps at moderate intensity, and to make steps for longer periods of time (minimal ten uninterrupted minutes). PMID:27207680

  17. A Study on Segmented Multiple-Step Forming of Doubly Curved Thick Plate by Reconfigurable Multi-Punch Dies

    SciTech Connect

    Ko, Young Ho; Han, Myoung Soo; Han, Jong Man

    2007-05-17

    Doubly curved thick plate forming in shipbuilding industries is currently performed by a thermal forming process, called as Line Heating by using gas flame torches. Due to the empirical manual work of it, the industries are eager for an alternative way to manufacture curved thick plates for ships. It was envisaged in this study to manufacture doubly curved thick plates by the multi-punch die forming. Experiments and finite element analyses were conducted to evaluate the feasibility of the reconfigurable discrete die forming to the thick plates. Single and segmented multiple step forming procedures were considered from both forming efficiency and accuracy. Configuration of the multi-punch dies suitable for the segmented multiple step forming was also explored. As a result, Segmented multiple step forming with matched dies had a limited formability when the objective shapes become complicate, while a unmatched die configuration provided better possibility to manufacture large curved plates for ships.

  18. Assembly and benign step-by-step post-treatment of oppositely charged reduced graphene oxides for transparent conductive thin films with multiple applications

    NASA Astrophysics Data System (ADS)

    Zhu, Jiayi; He, Junhui

    2012-05-01

    We report a new approach for the fabrication of flexible and transparent conducting thin films via the layer-by-layer (LbL) assembly of oppositely charged reduced graphene oxide (RGO) and the benign step-by-step post-treatment on substrates with a low glass-transition temperature, such as glass and poly(ethylene terephthalate) (PET). The RGO dispersions and films were characterized by means of atomic force microscopy, UV-visible absorption spectrophotometery, Raman spectroscopy, transmission electron microscopy, contact angle/interface systems and a four-point probe. It was found that the graphene thin films exhibited a significant increase in electrical conductivity after the step-by-step post-treatments. The graphene thin film on the PET substrate had a good conductivity retainability after multiple cycles (30 cycles) of excessively bending (bending angle: 180°), while tin-doped indium oxide (ITO) thin films on PET showed a significant decrease in electrical conductivity. In addition, the graphene thin film had a smooth surface with tunable wettability.We report a new approach for the fabrication of flexible and transparent conducting thin films via the layer-by-layer (LbL) assembly of oppositely charged reduced graphene oxide (RGO) and the benign step-by-step post-treatment on substrates with a low glass-transition temperature, such as glass and poly(ethylene terephthalate) (PET). The RGO dispersions and films were characterized by means of atomic force microscopy, UV-visible absorption spectrophotometery, Raman spectroscopy, transmission electron microscopy, contact angle/interface systems and a four-point probe. It was found that the graphene thin films exhibited a significant increase in electrical conductivity after the step-by-step post-treatments. The graphene thin film on the PET substrate had a good conductivity retainability after multiple cycles (30 cycles) of excessively bending (bending angle: 180°), while tin-doped indium oxide (ITO) thin films on

  19. Mesenchymal stem cells secretomes' affect multiple myeloma translation initiation.

    PubMed

    Marcus, H; Attar-Schneider, O; Dabbah, M; Zismanov, V; Tartakover-Matalon, S; Lishner, M; Drucker, L

    2016-06-01

    Bone marrow mesenchymal stem cells' (BM-MSCs) role in multiple myeloma (MM) pathogenesis is recognized. Recently, we have published that co-culture of MM cell lines with BM-MSCs results in mutual modulation of phenotype and proteome (via translation initiation (TI) factors eIF4E/eIF4GI) and that there are differences between normal donor BM-MSCs (ND-MSCs) and MM BM-MSCs (MM-MSCs) in this crosstalk. Here, we aimed to assess the involvement of soluble BM-MSCs' (ND, MM) components, more easily targeted, in manipulation of MM cell lines phenotype and TI with specific focus on microvesicles (MVs) capable of transferring critical biological material. We applied ND and MM-MSCs 72h secretomes to MM cell lines (U266 and ARP-1) for 12-72h and then assayed the cells' (viability, cell count, cell death, proliferation, cell cycle, autophagy) and TI (factors: eIF4E, teIF4GI; regulators: mTOR, MNK1/2, 4EBP; targets: cyclin D1, NFκB, SMAD5, cMyc, HIF1α). Furthermore, we dissected the secretome into >100kDa and <100kDa fractions and repeated the experiments. Finally, MVs were isolated from the ND and MM-MSCs secretomes and applied to MM cell lines. Phenotype and TI were assessed. Secretomes of BM-MSCs (ND, MM) significantly stimulated MM cell lines' TI, autophagy and proliferation. The dissected secretome yielded different effects on MM cell lines phenotype and TI according to fraction (>100kDa- repressed; <100kDa- stimulated) but with no association to source (ND, MM). Finally, in analyses of MVs extracted from BM-MSCs (ND, MM) we witnessed differences in accordance with source: ND-MSCs MVs inhibited proliferation, autophagy and TI whereas MM-MSCs MVs stimulated them. These observations highlight the very complex communication between MM and BM-MSCs and underscore its significance to major processes in the malignant cells. Studies into the influential MVs cargo are underway and expected to uncover targetable signals in the regulation of the TI/proliferation/autophagy cascade

  20. Multiple dietary supplements do not affect metabolic and cardiovascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2013-09-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24036417

  1. Multiple controls affect arsenite oxidase gene expression in Herminiimonas arsenicoxydans

    PubMed Central

    2010-01-01

    Background Both the speciation and toxicity of arsenic are affected by bacterial transformations, i.e. oxidation, reduction or methylation. These transformations have a major impact on environmental contamination and more particularly on arsenic contamination of drinking water. Herminiimonas arsenicoxydans has been isolated from an arsenic- contaminated environment and has developed various mechanisms for coping with arsenic, including the oxidation of As(III) to As(V) as a detoxification mechanism. Results In the present study, a differential transcriptome analysis was used to identify genes, including arsenite oxidase encoding genes, involved in the response of H. arsenicoxydans to As(III). To get insight into the molecular mechanisms of this enzyme activity, a Tn5 transposon mutagenesis was performed. Transposon insertions resulting in a lack of arsenite oxidase activity disrupted aoxR and aoxS genes, showing that the aox operon transcription is regulated by the AoxRS two-component system. Remarkably, transposon insertions were also identified in rpoN coding for the alternative N sigma factor (σ54) of RNA polymerase and in dnaJ coding for the Hsp70 co-chaperone. Western blotting with anti-AoxB antibodies and quantitative RT-PCR experiments allowed us to demonstrate that the rpoN and dnaJ gene products are involved in the control of arsenite oxidase gene expression. Finally, the transcriptional start site of the aoxAB operon was determined using rapid amplification of cDNA ends (RACE) and a putative -12/-24 σ54-dependent promoter motif was identified upstream of aoxAB coding sequences. Conclusion These results reveal the existence of novel molecular regulatory processes governing arsenite oxidase expression in H. arsenicoxydans. These data are summarized in a model that functionally integrates arsenite oxidation in the adaptive response to As(III) in this microorganism. PMID:20167112

  2. Multiple dietary supplements do not affect metabolic and cardiovascular health

    PubMed Central

    Holloszy, John O.; Fontana, Luigi

    2014-01-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  3. Multiple steps in the regulation of transcription-factor level and activity.

    PubMed Central

    Calkhoven, C F; Ab, G

    1996-01-01

    This review focuses on the regulation of transcription factors, many of which are DNA-binding proteins that recognize cis-regulatory elements of target genes and are the most direct regulators of gene transcription. Transcription factors serve as integration centres of the different signal-transduction pathways affecting a given gene. It is obvious that the regulation of these regulators themselves is of crucial importance for differential gene expression during development and in terminally differentiated cells. Transcription factors can be regulated at two, principally different, levels, namely concentration and activity, each of which can be modulated in a variety of ways. The concentrations of transcription factors, as of intracellular proteins in general, may be regulated at any of the steps leading from DNA to protein, including transcription, RNA processing, mRNA degradation and translation. The activity of a transcription factor is often regulated by (de) phosphorylation, which may affect different functions, e.g. nuclear localization DNA binding and trans-activation. Ligand binding is another mode of transcription-factor activation. It is typical for the large super-family of nuclear hormone receptors. Heterodimerization between transcription factors adds another dimension to the regulatory diversity and signal integration. Finally, non-DNA-binding (accessory) factors may mediate a diverse range of functions, e.g. serving as a bridge between the transcription factor and the basal transcription machinery, stabilizing the DNA-binding complex or changing the specificity of the target sequence recognition. The present review presents an overview of different modes of transcription-factor regulation, each illustrated by typical examples. PMID:8713055

  4. Applying the 5-Step Method to Children and Affected Family Members: Opportunities and Challenges within Policy and Practice

    ERIC Educational Resources Information Center

    Harwin, Judith

    2010-01-01

    The main aim of this article is to consider how the 5-Step Method could be developed to meet the needs of affected family members (AFMs) with children under the age of 18. This would be an entirely new development. This article examines opportunities and challenges within practice and policy and makes suggestions on how the Method could be taken…

  5. 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…

  6. The First Step to Success Program: An Analysis of Outcomes with Identical Twins across Multiple Baselines.

    ERIC Educational Resources Information Center

    Golly, Annemieke; Sprague, Jeffrey; Walker, Hill; Beard, Kelli; Gorham, Ginger

    2000-01-01

    Two studies evaluated effects of First Step to Success, a collaborative home and school early intervention program designed for kindergartners who show signs of emerging antisocial behavior. Two sets of 5-year-old male twins were the subjects of the 4-year studies. Exposure to the First Step program produced powerful behavior changes that were…

  7. The Telomerase Inhibitor MST-312 Interferes with Multiple Steps in the Herpes Simplex Virus Life Cycle

    PubMed Central

    Haberichter, Jarod; Roberts, Scott; Abbasi, Imran; Dedthanou, Phonphanh; Pradhan, Prajakta

    2015-01-01

    antivirals. One such factor, telomerase, is the cellular enzyme that synthesizes DNA repeats at the ends of chromosomes during replication to prevent DNA shortening. In this study, we investigate role of telomerase in HSV infection. The data demonstrate that the telomerase inhibitor MST-312 suppressed HSV replication at multiple steps of viral infection. PMID:26178994

  8. Cardiac Myosin Binding Protein C Phosphorylation Affects Cross-Bridge Cycle's Elementary Steps in a Site-Specific Manner

    PubMed Central

    Wang, Li; Sadayappan, Sakthivel; Kawai, Masakata

    2014-01-01

    Based on our recent finding that cardiac myosin binding protein C (cMyBP-C) phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302), DAD (Asp273-Ala282-Asp302), SAS (Ser273-Ala282-Ser302), and t/t (cMyBP-C null) genotypes, and the results were compared to transgenic mice expressing wide-type (WT) cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi), and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc), and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases. PMID:25420047

  9. Multiple time step molecular dynamics in the optimized isokinetic ensemble steered with the molecular theory of solvation: Accelerating with advanced extrapolation of effective solvation forces

    SciTech Connect

    Omelyan, Igor E-mail: omelyan@icmp.lviv.ua; Kovalenko, Andriy

    2013-12-28

    We develop efficient handling of solvation forces in the multiscale method of multiple time step molecular dynamics (MTS-MD) of a biomolecule steered by the solvation free energy (effective solvation forces) obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model complemented with the Kovalenko-Hirata closure approximation). To reduce the computational expenses, we calculate the effective solvation forces acting on the biomolecule by using advanced solvation force extrapolation (ASFE) at inner time steps while converging the 3D-RISM-KH integral equations only at large outer time steps. The idea of ASFE consists in developing a discrete non-Eckart rotational transformation of atomic coordinates that minimizes the distances between the atomic positions of the biomolecule at different time moments. The effective solvation forces for the biomolecule in a current conformation at an inner time step are then extrapolated in the transformed subspace of those at outer time steps by using a modified least square fit approach applied to a relatively small number of the best force-coordinate pairs. The latter are selected from an extended set collecting the effective solvation forces obtained from 3D-RISM-KH at outer time steps over a broad time interval. The MTS-MD integration with effective solvation forces obtained by converging 3D-RISM-KH at outer time steps and applying ASFE at inner time steps is stabilized by employing the optimized isokinetic Nosé-Hoover chain (OIN) ensemble. Compared to the previous extrapolation schemes used in combination with the Langevin thermostat, the ASFE approach substantially improves the accuracy of evaluation of effective solvation forces and in combination with the OIN thermostat enables a dramatic increase of outer time steps. We demonstrate on a fully flexible model of alanine dipeptide in aqueous solution that the MTS-MD/OIN/ASFE/3D-RISM-KH multiscale method of molecular dynamics

  10. A step towards understanding plant responses to multiple environmental stresses: a genome-wide study.

    PubMed

    Sewelam, Nasser; Oshima, Yoshimi; Mitsuda, Nobutaka; Ohme-Takagi, Masaru

    2014-09-01

    In natural habitats, especially in arid areas, plants are often simultaneously exposed to multiple abiotic stresses, such as salt, osmotic and heat stresses. However, most analyses of gene expression in stress responses examine individual stresses. In this report, we compare gene expression in individual and combined stresses. We show that combined stress treatments with salt, mannitol and heat induce a unique pattern of gene expression that is not a simple merge of the individual stress responses. Under multiple stress conditions, expression of most heat and salt stress-responsive genes increased to levels similar to or higher than those measured in single stress conditions, but osmotic stress-responsive genes increased to lower levels. Genes up-regulated to higher levels under multiple stress condition than single stress conditions include genes for heat shock proteins, heat shock regulators and late embryogenesis abundant proteins (LEAs), which protect other proteins from damage caused by stresses, suggesting their importance in multiple stress condition. Based on this analysis, we identify candidate genes for engineering crop plants tolerant to multiple stresses. PMID:24417440

  11. Multiple roles of the capsid protein in the early steps of HIV-1 infection.

    PubMed

    Fassati, Ariberto

    2012-12-01

    The early steps of HIV-1 infection starting after virus entry into cells up to integration of its genome into host chromosomes are poorly understood. From seminal work showing that HIV-1 and oncoretroviruses follow different steps in the early stages post-entry, significant advances have been made in recent years and an important role for the HIV-1 capsid (CA) protein, the constituent of the viral core, has emerged. CA appears to orchestrate several events, such as virus uncoating, recognition by restriction factors and the innate immune system. It also plays a role in nuclear import and integration of HIV-1 and has become a novel target for antiretroviral drugs. Here we describe the different functions of CA and how they may be integrated into one or more coherent models that illuminate the early events in HIV-1 infection and their relations with the host cell. PMID:23041358

  12. Evolution of phase transformations after multiple steps of marforming in Ti-rich Ni-Ti SMA

    NASA Astrophysics Data System (ADS)

    Paula, A. S.; Mahesh, K. K.; Braz Fernandes, F. M.

    2008-05-01

    The phase transformations associated with Shape Memory Effect (SME) can be one step, B19' (martensite) ↔ B2 (austenite), or two/multiple steps which include the intermediate R phase, depending on the thermal and thermomechanical history of the alloy. The transformation temperatures are generally observed above room temperature in Ti-rich Ni-Ti alloys, while those observed in Ni-rich alloys occur below room temperature. The goal of the present work is to investigate the phase transformations evolution in Ti-Rich Ni-Ti SMA (Ni-51 at % Ti) when subjected to two distinct thermal treatments (500°C for 30 minutes in air and 800°C for 300 minutes in vacuum) and subsequently multiple steps of marforming thermomechanical treatments intercalated with thermal treatments (500°C for 30 minutes in air) and subsequent four distinct final thermal treatments (400, 450, 500 or 600°C for 30 minutes in air). Further, the stability of phase transformations in the initial ten thermal cycles of these thermomechanically treated samples is also studied. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) were used to identify the transformation temperatures and the phases that are present after the thermomechanical treatments.

  13. The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development.

    PubMed

    Pignoni, F; Hu, B; Zavitz, K H; Xiao, J; Garrity, P A; Zipursky, S L

    1997-12-26

    Sine oculis (so) and eyes absent (eya) are required for Drosophila eye development and are founding members of the mammalian Six and Eya gene families. These genes have been proposed to act with eyeless (Pax6) to regulate eye development in vertebrates and invertebrates. so encodes a highly diverged homeobox transcription factor and eya encodes a novel nuclear protein. We demonstrate that So and Eya (1) regulate common steps in eye development including cell proliferation, patterning, and neuronal development; (2) synergize in inducing ectopic eyes; and (3) interact in yeast and in vitro through evolutionarily conserved domains. We propose that an So/Eya complex regulates multiple steps in eye development and functions within the context of a network of genes to specify eye tissue identity. PMID:9428512

  14. Mechanisms of ribosome stalling by SecM at multiple elongation steps

    PubMed Central

    Zhang, Jun; Pan, Xijiang; Yan, Kaige; Sun, Shan; Gao, Ning; Sui, Sen-Fang

    2015-01-01

    Regulation of translating ribosomes is a major component of gene expression control network. In Escherichia coli, ribosome stalling by the C-terminal arrest sequence of SecM regulates the SecA-dependent secretion pathway. Previous studies reported many residues of SecM peptide and ribosome exit tunnel are critical for stalling. However, the underlying molecular mechanism is still not clear at the atomic level. Here, we present two cryo-EM structures of the SecM-stalled ribosomes at 3.3–3.7 Å resolution, which reveal two different stalling mechanisms at distinct elongation steps of the translation cycle: one is due to the inactivation of ribosomal peptidyl-transferase center which inhibits peptide bond formation with the incoming prolyl-tRNA; the other is the prolonged residence of the peptidyl-RNA at the hybrid A/P site which inhibits the full-scale tRNA translocation. These results demonstrate an elegant control of translation cycle by regulatory peptides through a continuous, dynamic reshaping of the functional center of the ribosome. DOI: http://dx.doi.org/10.7554/eLife.09684.001 PMID:26670735

  15. A versatile bacterial expression vector designed for single-step cloning of multiple DNA fragments using homologous recombination.

    PubMed

    Holmberg, Mats A; Gowda, Naveen Kumar Chandappa; Andréasson, Claes

    2014-06-01

    Production of recombinant proteins is the starting point for biochemical and biophysical analyses and requires methodology to efficiently proceed from gene sequence to purified protein. While optimized strategies for the efficient cloning of single-gene fragments for bacterial expression is available, efficient multiple DNA fragment cloning still presents a challenge. To facilitate this step, we have developed an efficient cloning strategy based on yeast homologous recombination cloning (YHRC) into the new pET-based bacterial expression vector pSUMO-YHRC. The vector supports cloning for untagged expression as well as fusions to His6-SUMO or His6 tags. We demonstrate that YHRC from single PCR products of 6 independent genes into the vector results in virtually no background. Importantly, in a quantitative assay for functional expression we find that single-step YHRC of 7 DNA fragments can be performed with very high cloning efficiencies. The method and reagents described in this paper significantly simplifies the construction of expression plasmids from multiple DNA fragments, including complex gene fusions, chimeric genes and polycistronic constructs. PMID:24631626

  16. Using multiple risk factors to assess the behavioral, cognitive, and affective effects of learned helplessness.

    PubMed

    McKean, K J

    1994-03-01

    Rather than examining the effect of the pessimistic explanatory style on an outcome variable reflecting a single domain, I studied the effects of multiple learned-helplessness risk factors on behavioral, cognitive, and affective variables. Undergraduate students completed the Learned Helplessness Scale (Quinless & McDermott-Nelson, 1988) as a measure of their expectation of uncontrollability and the Explanatory Style Questionnaire (Peterson et al., 1982) to determine their explanations for both positive and negative events. Results revealed a significant effect for risk level, with students at greater risk of helplessness reporting significantly more procrastination, lower grade point averages, and more dysphoria. These results support the use of multiple risk factors representing all learned-helplessness precursors and the assessment of learned-helplessness deficits drawn simultaneously from behavioral, cognitive, and affective domains. PMID:8189396

  17. GreenCube: A Student Multiple Small Payload Project: A First Step

    NASA Astrophysics Data System (ADS)

    Bracikowski, P. J.; Fagrelius, P. A.; Siddiqui, M. U.; Lynch, K. A.; Millan, R. M.

    2008-12-01

    Based on the CubeSat Project, which is a small satellite prototype established by CalPoly and Stanford Universities, Dartmouth College undergraduates have built a prototype 10cm x 10 cm x 30cm payload, dubbed GreenCube. The prototype consists of a number of subsystems: a data acquisition and analysis computer, power source and regulatory circuits, telemetry, GPS, and instruments. The on-board instruments are a magnetometer and 6 thermocouples that are stand-ins for future devices. The telemetry system alone, acting as a simple beacon, was flown on a 30km bursting-balloon in early June 2008. The beacon signal, which we successfully monitored for the entire flight, transmitted temperature readings from a built-in temperature sensor. We also successfully recovered the payload after a parachute return. The June flight served as a trial run of our balloon team and payload systems, and future flights are planned to test the full payload. Our long-term science goals take two forms. The GreenCube prototype will be applicable as an instrument platform for auroral sounding rockets and for future CubeSat missions. We are interested in a sounding rocket involving the release of approximately 8 small sub-payloads from a main payload to be flown from Poker Flat Alaska. Each sub-payload would be untethered and independent from the main payload and communicate independently to the ground station. This type of mission would investigate the k-spectrum of density irregularities in the auroral ionosphere, for which we will substitute plasma density probes for the thermocouples. Before flying the small payloads on a sounding rocket, though, our next step will be to launch the entire GreenCube payload on a balloon and then from a student test rocket within the next two years.

  18. Automated brain volumetrics in multiple sclerosis: a step closer to clinical application

    PubMed Central

    Beadnall, H N; Hatton, S N; Bader, G; Tomic, D; Silva, D G

    2016-01-01

    Background Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. Methods MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. Results Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. Conclusions In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies. PMID:27071647

  19. Multiplicative and Additive Modulation of Neuronal Tuning with Population Activity Affects Encoded Information.

    PubMed

    Arandia-Romero, Iñigo; Tanabe, Seiji; Drugowitsch, Jan; Kohn, Adam; Moreno-Bote, Rubén

    2016-03-16

    Numerous studies have shown that neuronal responses are modulated by stimulus properties and also by the state of the local network. However, little is known about how activity fluctuations of neuronal populations modulate the sensory tuning of cells and affect their encoded information. We found that fluctuations in ongoing and stimulus-evoked population activity in primate visual cortex modulate the tuning of neurons in a multiplicative and additive manner. While distributed on a continuum, neurons with stronger multiplicative effects tended to have less additive modulation and vice versa. The information encoded by multiplicatively modulated neurons increased with greater population activity, while that of additively modulated neurons decreased. These effects offset each other so that population activity had little effect on total information. Our results thus suggest that intrinsic activity fluctuations may act as a "traffic light" that determines which subset of neurons is most informative. PMID:26924437

  20. Bringing large-scale multiple genome analysis one step closer: ScalaBLAST and beyond

    SciTech Connect

    Oehmen, Christopher S.; Sofia, Heidi J.; Baxter, Douglas; Szeto, Ernest; Hugenholtz, Philip; Kyrpides, Nikos; Markowitz, Victor; Straatsma, Tjerk P.

    2007-06-01

    -scale genomics projects. The rapid growth of genome resources such as IMG cannot be sustained without more powerful tools such as ScalaBLAST that use more effectively large scale computing resources to perform the core BLAST calculations. ScalaBLAST is a high performance computing algorithm designed to give high throughput BLAST results on high-end supercomputers. Other parallel sequence comparison applications have been developed4-6. However problems with scaling generally prevent these applications from being used for very large searches. ScalaBLAST7 is the first BLAST application to be both highly scaleable against the size of the database as well as the number of computer processors on high-end hardware and on commodity clusters. ScalaBLAST achieves high throughput by parsing a large collection of query sequences into independent subgroups. These smaller tasks are assigned to independent process groups. Efficient scaling is achieved by (transparently to the user) sharing only one copy of the target database across all processors using the Global Array toolkit 8, 9, which provides software implementation of shared memory interface. ScalaBLAST was initially deployed on the 1,960 processor MPP2 cluster in the Wiliam R. Wiley Environmental Molecular Sciences Laboratory at Pacific Northwest National Laboratory, and has since been ported to a variety of linux-based clusters and shared memory architectures, including SGI Altix, AMD opteron, and Intel Xeon-based clusters. Future targets include IBM BlueGene, Cray, and SGI Altix XE architectures. The importance of performing high-throughput calculations rapidly lies in the rate of growth of sequence data. For a genome sequencing center to provide multiple-genome comparison capabilities, it must keep pace with exponentially growing collection of protein data, both from its own genomes, and from the public genome information as well. As sequence data continues to grow exponentially, this challenge will only increase with time. Solving

  1. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS. PMID:23126275

  2. Does multiple paternity affect seed mass in angiosperms? An experimental test in Dalechampia scandens.

    PubMed

    Pélabon, C; Albertsen, E; Falahati-Anbaran, M; Wright, J; Armbruster, W S

    2015-09-01

    Flowers fertilized by multiple fathers may be expected to produce heavier seeds than those fertilized by a single father. However, the adaptive mechanisms leading to such differences remain unclear, and the evidence inconsistent. Here, we first review the different hypotheses predicting an increase in seed mass when multiple paternity occurs. We show that distinguishing between these hypotheses requires information about average seed mass, but also about within-fruit variance in seed mass, bias in siring success among pollen donors, and whether siring success and seed mass are correlated. We then report the results of an experiment on Dalechampia scandens (Euphorbiaceae), assessing these critical variables in conjunction with a comparison of seed mass resulting from crosses with single vs. multiple pollen donors. Siring success differed among males when competing for fertilization, but average seed mass was not affected by the number of fathers. Furthermore, paternal identity explained only 3.8% of the variance in seed mass, and siring success was not correlated with the mass of the seeds produced. Finally, within-infructescence variance in seed mass was not affected by the number of fathers. These results suggest that neither differential allocation nor sibling rivalry has any effect on the average mass of seeds in multiply sired fruits in D. scandens. Overall, the limited paternal effects observed in most studies and the possibility of diversification bet hedging among flowers (but not within flowers), suggest that multiple paternity within fruits or infructescence is unlikely to affect seed mass in a large number of angiosperm species. PMID:26174371

  3. Filtering for networked control systems with single/multiple measurement packets subject to multiple-step measurement delays and multiple packet dropouts

    NASA Astrophysics Data System (ADS)

    Moayedi, Maryam; Foo, Yung Kuan; Chai Soh, Yeng

    2011-03-01

    The minimum-variance filtering problem in networked control systems, where both random measurement transmission delays and packet dropouts may occur, is investigated in this article. Instead of following the many existing results that solve the problem by using probabilistic approaches based on the probabilities of the uncertainties occurring between the sensor and the filter, we propose a non-probabilistic approach by time-stamping the measurement packets. Both single-measurement and multiple measurement packets are studied. We also consider the case of burst arrivals, where more than one packet may arrive between the receiver's previous and current sampling times; the scenario where the control input is non-zero and subject to delays and packet dropouts is examined as well. It is shown that, in such a situation, the optimal state estimate would generally be dependent on the possible control input. Simulations are presented to demonstrate the performance of the various proposed filters.

  4. Simultaneous determination of three species with a single-injection step using batch injection analysis with multiple pulse amperometric detection.

    PubMed

    Freitas, Jhonys Machado; Oliveira, Thiago da Costa; Gimenes, Denise Tofanello; Munoz, Rodrigo Alejandro Abarza; Richter, Eduardo Mathias

    2016-01-01

    In this work, the possibility of simultaneous determination of three compounds with a single-injection step using batch injection analysis with multiple pulse amperometric detection (BIA-MPA) is demonstrated for the first time. A sequence of three potential pulses (+1.25 V, +1.60 V, and +1.80 V) was applied with the acquisition of three separate amperograms. 8-Chlorotheophylline was detected selectively at +1.25 V, both 8-chlorotheophylline and pyridoxine at +1.60V and 8-chlorotheophylline, pyridoxine, and diphenhydramine at +1.80 V. Subtraction between the currents detected at the three amperograms (with the help of correction factors) was used for the selective determination of pyridoxine and diphenhydramine. The proposed method is simple, inexpensive, fast (60 injections h(-1)), and present selectivity for the determination of the three compounds in pharmaceutical samples, with results similar to those obtained by HPLC (95% confidence level). PMID:26695316

  5. Parasites and health affect multiple sexual signals in male common wall lizards, Podarcis muralis

    NASA Astrophysics Data System (ADS)

    Martín, José; Amo, Luisa; López, Pilar

    2008-04-01

    Multiple advertising sexual traits may either advertise different characteristics of male condition or be redundant to reinforce reliability of signals. Research has focused on multiple visual traits. However, in animals that use different multiple additional sensory systems, such as chemoreception, different types of traits might have evolved to signal similar characteristics of a male quality using different sensory channels. We examined whether ventral coloration and chemicals in femoral gland secretions of male common wall lizards, Podarcis muralis, are affected by their health state (blood-parasite load and cell-mediated immune response). Our results indicated that less parasitized lizards had brighter and more yellowish ventral colorations and also femoral secretions with higher proportions of two esters of octadecenoic acid. In addition, lizards with a greater immune response had more saturated coloration and secretions with higher proportions of octadecenoic acid methyl ester. We suggest that these signals would be reliable because only healthier males seemed able to allocate more carotenoids to coloration and presumably costly chemicals to secretions. The use of multiple sensory channels may provide more opportunities to signal a male quality under different circumstances, but also may reinforce the reliability of the signal when both types of traits may be perceived simultaneously.

  6. Step-response of a torsional device with multiple discontinuous non-linearities: Formulation of a vibratory experiment

    NASA Astrophysics Data System (ADS)

    Krak, Michael D.; Dreyer, Jason T.; Singh, Rajendra

    2016-03-01

    A vehicle clutch damper is intentionally designed to contain multiple discontinuous non-linearities, such as multi-staged springs, clearances, pre-loads, and multi-staged friction elements. The main purpose of this practical torsional device is to transmit a wide range of torque while isolating torsional vibration between an engine and transmission. Improved understanding of the dynamic behavior of the device could be facilitated by laboratory measurement, and thus a refined vibratory experiment is proposed. The experiment is conceptually described as a single degree of freedom non-linear torsional system that is excited by an external step torque. The single torsional inertia (consisting of a shaft and torsion arm) is coupled to ground through parallel production clutch dampers, which are characterized by quasi-static measurements provided by the manufacturer. Other experimental objectives address physical dimensions, system actuation, flexural modes, instrumentation, and signal processing issues. Typical measurements show that the step response of the device is characterized by three distinct non-linear regimes (double-sided impact, single-sided impact, and no-impact). Each regime is directly related to the non-linear features of the device and can be described by peak angular acceleration values. Predictions of a simplified single degree of freedom non-linear model verify that the experiment performs well and as designed. Accordingly, the benchmark measurements could be utilized to validate non-linear models and simulation codes, as well as characterize dynamic parameters of the device including its dissipative properties.

  7. Multi-step Preparation Technique to Recover Multiple Metabolite Compound Classes for In-depth and Informative Metabolomic Analysis

    PubMed Central

    Cruickshank-Quinn, Charmion; Quinn, Kevin D.; Powell, Roger; Yang, Yanhui; Armstrong, Michael; Mahaffey, Spencer; Reisdorph, Richard; Reisdorph, Nichole

    2014-01-01

    Metabolomics is an emerging field which enables profiling of samples from living organisms in order to obtain insight into biological processes. A vital aspect of metabolomics is sample preparation whereby inconsistent techniques generate unreliable results. This technique encompasses protein precipitation, liquid-liquid extraction, and solid-phase extraction as a means of fractionating metabolites into four distinct classes. Improved enrichment of low abundance molecules with a resulting increase in sensitivity is obtained, and ultimately results in more confident identification of molecules. This technique has been applied to plasma, bronchoalveolar lavage fluid, and cerebrospinal fluid samples with volumes as low as 50 µl.  Samples can be used for multiple downstream applications; for example, the pellet resulting from protein precipitation can be stored for later analysis. The supernatant from that step undergoes liquid-liquid extraction using water and strong organic solvent to separate the hydrophilic and hydrophobic compounds. Once fractionated, the hydrophilic layer can be processed for later analysis or discarded if not needed. The hydrophobic fraction is further treated with a series of solvents during three solid-phase extraction steps to separate it into fatty acids, neutral lipids, and phospholipids. This allows the technician the flexibility to choose which class of compounds is preferred for analysis. It also aids in more reliable metabolite identification since some knowledge of chemical class exists. PMID:25045913

  8. Computer-Based Video Instruction to Teach Young Adults with Moderate Intellectual Disabilities to Perform Multiple Step, Job Tasks in a Generalized Setting

    ERIC Educational Resources Information Center

    Mechling, Linda C.; Ortega-Hurndon, Fanny

    2007-01-01

    This study evaluated the effectiveness of computer-based video instruction (CBVI) to teach three young adults with moderate intellectual disabilities to perform complex, multiple step, job tasks in a generalized setting. A multiple probe design across three job tasks and replicated across three students was used to evaluate the effectiveness of…

  9. Intraneural perineurioma affecting multiple nerves: a case report and literature review.

    PubMed

    Wang, Lei-Ming; Zhong, Yan-Feng; Zheng, Dan-Feng; Sun, A-Ping; Zhang, Ying-Shuang; Dong, Rong-Fang; Pan, Yi

    2014-01-01

    Intraneural perineurioma is a neoplasm of perineurial cells, corresponding to WHO grade I. We present a case of intraneural perineurioma affecting multiple nerves, which usually involved one or two of major nerve trunks in one patient. We describe the clinical presentation, magnetic resonance (MR) neurography characteristics, and pathological characteristics. The differential diagnosis with other diseases, such as neurofibroma, Schwannomatosis and HNPP, will also be discussed. We also review the literature in efforts to highlight recent studies on intraneural perineurioma and heighten and awareness for the possible presentations of this disorder. PMID:25031759

  10. Intraneural perineurioma affecting multiple nerves: a case report and literature review

    PubMed Central

    Wang, Lei-Ming; Zhong, Yan-Feng; Zheng, Dan-Feng; Sun, A-Ping; Zhang, Ying-Shuang; Dong, Rong-Fang; Pan, Yi

    2014-01-01

    Intraneural perineurioma is a neoplasm of perineurial cells, corresponding to WHO grade I. We present a case of intraneural perineurioma affecting multiple nerves, which usually involved one or two of major nerve trunks in one patient. We describe the clinical presentation, magnetic resonance (MR) neurography characteristics, and pathological characteristics. The differential diagnosis with other diseases, such as neurofibroma, Schwannomatosis and HNPP, will also be discussed. We also review the literature in efforts to highlight recent studies on intraneural perineurioma and heighten and awareness for the possible presentations of this disorder. PMID:25031759

  11. The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies

    PubMed Central

    Freeman, Brian C.; Felts, Sara J.; Toft, David O.; Yamamoto, Keith R.

    2000-01-01

    Multiple molecular chaperones, including Hsp90 and p23, interact with members of the intracellular receptor (IR) family. To investigate p23 function, we compared the effects of three p23 proteins on IR activities, yeast p23 (sba1p) and the two human p23 homologs, p23 and tsp23. We found that Sba1p was indistinguishable from human p23 in assays of seven IR activities in both animal cells and in yeast; in contrast, certain effects of tsp23 were specific to that homolog. Transcriptional activation by two IRs was increased by expression of any of the p23 species, whereas activation by five other IRs was decreased by Sba1p or p23, and unaffected by tsp23. p23 was expressed in all tissues examined except striated and cardiac muscle, whereas tsp23 accumulated in a complementary pattern; hence, p23 proteins might contribute to tissue-specific differences in IR activities. Unlike Hsp90, which acts on IR aporeceptors to stimulate ligand potency (i.e., hormone-binding affinity), p23 proteins acted on IR holoreceptors to alter ligand efficiencies (i.e., transcriptional activation activity). Moreover, the p23 effects developed slowly, requiring prolonged exposure to hormone. In vitro, p23 interacted preferentially with hormone–receptor–response element ternary complexes, and stimulated receptor–DNA dissociation. The dissociation was reversed by addition of a fragment of the GRIP1 coactivator, suggesting that the two reactions may be in competition in vivo. Our findings suggest that p23 functions at one or more late steps in IR-mediated signal transduction, perhaps including receptor recycling and/or reversal of the response. PMID:10691735

  12. Multiple sublethal chemicals negatively affect tadpoles of the green frog, Rana clamitans

    USGS Publications Warehouse

    Boone, Michelle D.; Bridges, Christine M.; Fairchild, James F.; Little, Edward E.

    2005-01-01

    Many habitats may be exposed to multiple chemical contaminants, particularly in agricultural areas where fertilizer and pesticide use are common; however, the singular and interactive effects of contaminants are not well understood. The objective of our study was to examine how realistic, sublethal environmental levels of ammonium nitrate fertilizer (0, 10, 20 mg/L and ammonium chloride control) and the common insecticide carbaryl (0 or 2.5 mg/L) individually and interactively affect the development, size, and survival of green frog (Rana clamitans) tadpoles. We reared tadpoles for 95 d in outdoor 1,000-L polyethylene ponds. We found that the combination of carbaryl and nitrate had a negative effect on development and mass of tadpoles compared to the positive effect that either contaminant had alone. Presence of carbaryl was generally associated with short-term increases in algal resources, including ponds exposed to both carbaryl and nitrate. However, with exposure to nitrate and carbaryl, tadpole mass and development were not positively affected as with one chemical stressor alone. The combination of these sublethal contaminants may reduce the ability of amphibians to benefit from food-rich environments or have metabolic costs. Our study demonstrates the importance of considering multiple stressors when evaluating population-level responses.

  13. Hydrogeological factors affecting the multiple plumes of chlorinated contaminants in an industrial complex, Wonju, Korea

    NASA Astrophysics Data System (ADS)

    Yang, J.; Kaown, D.; Lee, H.; Lee, K.

    2010-12-01

    Apparent plume attenuations of multiple chlorinated contaminants such as TCE, carbon tetrachloride, and its daughter products at an industrial complex, Wonju, Korea were examined through various hydraulic tests and six rounds of groundwater quality analyses. Aquifer media properties and hydrogeologic factors affecting the distribution and attenuation of multiple contaminants were investigated and key attributes were evaluated. The study area has vertically heterogeneous properties from top alluvial layer to crystalline rocks while the weathered fractured layer above intact Jurassic biotite granite acts as the main layer for groundwater flow and aqueous phase multiple contaminants migration. Aerial heterogeneity in surface conditions plays an important role for groundwater recharge because the industrial complex is mostly paved by asphalt and concrete. Due to limited recharge area and concentrated precipitation in summer season, seasonal effects of contaminant plume distribution diminish as the distance increase from the area of recharge. This study analyzed how differently the solute and contaminant concentrations response to the seasonal recharge. For the analyses, the study site was divided into three zones and four transects were established. Groundwater and solute mass balances were estimated by computing groundwater and solute mass flux through transects. The effects of groundwater pumping, groundwater flow and contaminant degradation were examined to simulate the solutes and contaminant concentrations. General tendency of the water quality and contaminant concentration were reproducible with the effects of major components such as groundwater recharge, pumping and estimated degradation rate.

  14. Unmet Needs of Patients Feeling Severely Affected by Multiple Sclerosis in Germany: A Qualitative Study

    PubMed Central

    Golla, Heidrun; Strupp, Julia; Karbach, Ute; Kaiser, Claudia; Ernstmann, Nicole; Pfaff, Holger; Ostgathe, Christoph; Voltz, Raymond

    2014-01-01

    Abstract Background: The needs of patients feeling severely affected by multiple sclerosis (MS) have rarely been investigated. However this is essential information to know before care can be improved, including adding palliative care (PC) services where helpful. Since it remains unclear at what point specialized palliative care should begin for this patient group, this study focuses on needs in general. Objective: The objective was to explore the subjectively unmet needs of patients feeling severely affected by MS. Methods: The study used a qualitative cross-sectional approach for needs assessment. Fifteen patients self-reporting feeling severely affected by MS were recruited and interviewed using a combination of purposive and convenience sampling (five were accompanied by a caregiver relative). Interviews were recorded and transcribed verbatim, followed by qualitative content analysis. Results: Unmet needs were identified in the main categories “support of family and friends,” “health care services,” “managing everyday life,” and “maintaining biographical continuity.” Patients expressed the desire for more support from their families and to be viewed as distinct individuals. They see a substantial deficit in the physician-patient relationship and in the coordination of services. A decrease in expressed unmet needs was found for patients more severely affected and less socially integrated. Conclusions: To address the unmet needs of severely affected MS patients, health care services need to be improved and linked with existing PC services. Special attention is required to form supporting professional-patient relationships. Multiprofessional services should be accessible for patients, while integrating relatives. All services should have an individual approach to provide needs-tailored support. PMID:24527993

  15. Inflammatory Proprotein Convertase-Matrix Metalloproteinase Proteolytic Pathway in Antigen-presenting Cells as a Step to Autoimmune Multiple Sclerosis*

    PubMed Central

    Shiryaev, Sergey A.; Remacle, Albert G.; Savinov, Alexei Y.; Chernov, Andrei V.; Cieplak, Piotr; Radichev, Ilian A.; Williams, Roy; Shiryaeva, Tatiana N.; Gawlik, Katarzyna; Postnova, Tatiana I.; Ratnikov, Boris I.; Eroshkin, Alexei M.; Motamedchaboki, Khatereh; Smith, Jeffrey W.; Strongin, Alex Y.

    2009-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system with autoimmune etiology. Susceptibility to MS is linked to viral and bacterial infections. Matrix metalloproteinases (MMPs) play a significant role in the fragmentation of myelin basic protein (MBP) and demyelination. The splice variants of the single MBP gene are expressed in the oligodendrocytes of the central nervous system (classic MBP) and in the immune cells (Golli-MBPs). Our data suggest that persistent inflammation caused by environmental risk factors is a step to MS. We have discovered biochemical evidence suggesting the presence of the inflammatory proteolytic pathway leading to MS. The pathway involves the self-activated furin and PC2 proprotein convertases and membrane type-6 MMP (MT6-MMP/MMP-25) that is activated by furin/PC2. These events are followed by MMP-25 proteolysis of the Golli-MBP isoforms in the immune system cells and stimulation of the specific autoimmune T cell clones. It is likely that the passage of these autoimmune T cell clones through the disrupted blood-brain barrier to the brain and the recognition of neuronal, classic MBP causes inflammation leading to the further up-regulation of the activity of the multiple individual MMPs, the massive cleavage of MBP in the brain, demyelination, and MS. In addition to the cleavage of Golli-MBPs, MMP-25 proteolysis readily inactivates crystallin αB that is a suppressor of MS. These data suggest that MMP-25 plays an important role in MS pathology and that MMP-25, especially because of its restricted cell/tissue expression pattern and cell surface/lipid raft localization, is a promising drug target in MS. PMID:19726693

  16. Inflammatory proprotein convertase-matrix metalloproteinase proteolytic pathway in antigen-presenting cells as a step to autoimmune multiple sclerosis.

    PubMed

    Shiryaev, Sergey A; Remacle, Albert G; Savinov, Alexei Y; Chernov, Andrei V; Cieplak, Piotr; Radichev, Ilian A; Williams, Roy; Shiryaeva, Tatiana N; Gawlik, Katarzyna; Postnova, Tatiana I; Ratnikov, Boris I; Eroshkin, Alexei M; Motamedchaboki, Khatereh; Smith, Jeffrey W; Strongin, Alex Y

    2009-10-30

    Multiple sclerosis (MS) is a disease of the central nervous system with autoimmune etiology. Susceptibility to MS is linked to viral and bacterial infections. Matrix metalloproteinases (MMPs) play a significant role in the fragmentation of myelin basic protein (MBP) and demyelination. The splice variants of the single MBP gene are expressed in the oligodendrocytes of the central nervous system (classic MBP) and in the immune cells (Golli-MBPs). Our data suggest that persistent inflammation caused by environmental risk factors is a step to MS. We have discovered biochemical evidence suggesting the presence of the inflammatory proteolytic pathway leading to MS. The pathway involves the self-activated furin and PC2 proprotein convertases and membrane type-6 MMP (MT6-MMP/MMP-25) that is activated by furin/PC2. These events are followed by MMP-25 proteolysis of the Golli-MBP isoforms in the immune system cells and stimulation of the specific autoimmune T cell clones. It is likely that the passage of these autoimmune T cell clones through the disrupted blood-brain barrier to the brain and the recognition of neuronal, classic MBP causes inflammation leading to the further up-regulation of the activity of the multiple individual MMPs, the massive cleavage of MBP in the brain, demyelination, and MS. In addition to the cleavage of Golli-MBPs, MMP-25 proteolysis readily inactivates crystallin alphaB that is a suppressor of MS. These data suggest that MMP-25 plays an important role in MS pathology and that MMP-25, especially because of its restricted cell/tissue expression pattern and cell surface/lipid raft localization, is a promising drug target in MS. PMID:19726693

  17. Multiple Model Adaptive Two-Step Filter and Motion Tracking Sliding-Mode Guidance for Missiles with Time Lag in Acceleration

    NASA Astrophysics Data System (ADS)

    Zhou, Di; Zhang, Yong-An; Duan, Guang-Ren

    The two-step filter has been combined with a modified Sage-Husa time-varying measurement noise statistical estimator, which is able to estimate the covariance of measurement noise on line, to generate an adaptive two-step filter. In many practical applications such as the bearings-only guidance, some model parameters and the process noise covariance are also unknown a priori. Based on the adaptive two-step filter, we utilize multiple models in the first-step filtering as well as in the time update of the second-step filtering to handle the uncertainties of model parameters and process noise covariance. In each timestep of the multiple model filtering, probabilistic weights punishing the estimates of first-step state from different models, and their associated covariance matrices are acquired according to Bayes’ rule. The weighted sum of the estimates of first-step state and that of the associated covariance matrices are extracted as the ultimate estimate and covariance of the first-step state, and are used as measurement information for the measurement update of the second-step state. Thus there is still only one iteration process and no apparent enhancement of computation burden. A motion tracking sliding-mode guidance law is presented for missiles with non-negligible delays in actual acceleration. This guidance law guarantees guidance accuracy and is able to enhance observability in bearings-only tracking. In bearings-only cases, the multiple model adaptive two-step filter is applied to the motion tracking sliding-mode guidance law, supplying relative range, relative velocity, and target acceleration information. In simulation experiments satisfactory filtering and guidance results are obtained, even if the filter runs into unknown target maneuvers and unknown time-varying measurement noise covariance, and the guidance law has to deal with a large time lag in acceleration.

  18. The K+ battery-regulating Arabidopsis K+ channel AKT2 is under the control of multiple post-translational steps

    PubMed Central

    Michard, Erwan; Rocha, Marcio; Gomez-Porras, Judith L; González, Wendy; Corrâa, Luiz Gustavo Guedes; Ramírez-Aguilar, Santiago J; Cuin, Tracey Ann

    2011-01-01

    Potassium (K+) is an important nutrient for plants. It serves as a cofactor of various enzymes and as the major inorganic solute maintaining plant cell turgor. In a recent study, an as yet unknown role of K+ in plant homeostasis was shown. It was demonstrated that K+ gradients in vascular tissues can serve as an energy source for phloem (re)loading processes and that the voltage-gated K+ channels of the AKT2-type play a unique role in this process. The AKT2 channel can be converted by phosphorylation of specific serine residues (S210 and S329) into a non-rectifying channel that allows a rapid efflux of K+ from the sieve element/companion cells (SE/CC) complex. The energy of this flux is used by other transporters for phloem (re)loading processes. Nonetheless, the results do indicate that post-translational modifications at S210 and S329 alone cannot explain AKT2 regulation. Here, we discuss the existence of multiple post-translational modification steps that work in concert to convert AKT2 from an inward-rectifying into a non-rectifying K+ channel. PMID:21445013

  19. Inferring rare disease risk variants based on exact probabilities of sharing by multiple affected relatives

    PubMed Central

    Bureau, Alexandre; Younkin, Samuel G.; Parker, Margaret M.; Bailey-Wilson, Joan E.; Marazita, Mary L.; Murray, Jeffrey C.; Mangold, Elisabeth; Albacha-Hejazi, Hasan; Beaty, Terri H.; Ruczinski, Ingo

    2014-01-01

    Motivation: Family-based designs are regaining popularity for genomic sequencing studies because they provide a way to test cosegregation with disease of variants that are too rare in the population to be tested individually in a conventional case–control study. Results: Where only a few affected subjects per family are sequenced, the probability that any variant would be shared by all affected relatives—given it occurred in any one family member—provides evidence against the null hypothesis of a complete absence of linkage and association. A P-value can be obtained as the sum of the probabilities of sharing events as (or more) extreme in one or more families. We generalize an existing closed-form expression for exact sharing probabilities to more than two relatives per family. When pedigree founders are related, we show that an approximation of sharing probabilities based on empirical estimates of kinship among founders obtained from genome-wide marker data is accurate for low levels of kinship. We also propose a more generally applicable approach based on Monte Carlo simulations. We applied this method to a study of 55 multiplex families with apparent non-syndromic forms of oral clefts from four distinct populations, with whole exome sequences available for two or three affected members per family. The rare single nucleotide variant rs149253049 in ADAMTS9 shared by affected relatives in three Indian families achieved significance after correcting for multiple comparisons (p=2×10−6). Availability and implementation: Source code and binaries of the R package RVsharing are freely available for download at http://cran.r-project.org/web/packages/RVsharing/index.html. Contact: alexandre.bureau@msp.ulaval.ca or ingo@jhu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24740360

  20. Pain and affective memory biases interact to predict depressive symptoms in multiple sclerosis.

    PubMed

    Bruce, J M; Polen, D; Arnett, P A

    2007-01-01

    A large literature supports a direct relationship between pain and depressive symptoms among various patient populations. Patients with multiple sclerosis (MS) frequently experience both pain and depression. Despite this, no relationship between pain and depression has been found in MS. The present investigation explored the relationship between pain and depression in a sample of patients with MS. Consistent with cognitive theories of depression, results supported the hypothesis that pain would only contribute to depression when MS patients exhibited a concomitant cognitive vulnerability. Cognitive vulnerability to depression was measured using a performance based affective memory bias (AMB) task. Patients with high levels of pain and negative AMB reported more depressive symptoms compared to patients with pain and positive AMB. Implications for the identification and treatment of depression in MS are discussed. PMID:17294612

  1. Eating in groups: Do multiple social influences affect intake in a fast-food restaurant?

    PubMed

    Brindal, Emily; Wilson, Carlene; Mohr, Philip; Wittert, Gary

    2015-05-01

    This study investigated multiple social influences to determine whether they affect amount eaten at a fast-food environment. Using observational methods, data on meal duration, foods eaten and personal characteristics were collected for 157 McDonald's patrons. Analysis of covariance revealed that female diners ate less kilojoules when eating in mixed- versus same-sex groups (adjusted difference = 967 kJ, p < .05), while male diners eating in mixed-sex company ate more in groups compared to pairs (adjusted difference = 1067 kJ, p = .019). Influences to increase and restrict the amount eaten can operate simultaneously in an eating environment with gender a critical factor for consideration. PMID:25903236

  2. Detecting Differential Item Functioning in the Japanese Version of the Multiple Affect Adjective Check List--Revised

    ERIC Educational Resources Information Center

    Yasuda, Tomoyuki; Lei, Pui-Wa; Suen, Hoi K.

    2007-01-01

    This study examines the differential item functioning (DIF) of the English version and the Japanese-translated version of the Multiple Affect Adjective Check List--Revised (MAACL-R) using the logistic regression (LR) procedure. The results of the LR are supplemented by multiple group confirmatory factor analysis (MGCFA). A total of five items are…

  3. Use of multiple correspondence analysis (MCA) to identify interactive meteorological conditions affecting relative throughfall

    NASA Astrophysics Data System (ADS)

    Van Stan, John T.; Gay, Trent E.; Lewis, Elliott S.

    2016-02-01

    Forest canopies alter rainfall reaching the surface by redistributing it as throughfall. Throughfall supplies water and nutrients to a variety of ecohydrological components (soil microbial communities, stream water discharge/chemistry, and stormflow pathways) and is controlled by canopy structural interactions with meteorological conditions across temporal scales. This work introduces and applies multiple correspondence analyses (MCAs) to a range of meteorological thresholds (median intensity, median absolute deviation (MAD) of intensity, median wind-driven droplet inclination angle, and MAD of wind speed) for an example throughfall problem: identification of interacting storm conditions corresponding to temporal concentration in relative throughfall beyond the median observation (⩾73% of rain). MCA results from the example show that equalling or exceeding rain intensity thresholds (median and MAD) corresponded with temporal concentration of relative throughfall across all storms. Under these intensity conditions, two wind mechanisms produced significant correspondences: (1) high, steady wind-driven droplet inclination angles increased surface wetting; and (2) sporadic winds shook entrained droplets from surfaces. A discussion is provided showing that these example MCA findings agree well with previous work relying on more historically common methods (e.g., multiple regression and analytical models). Meteorological threshold correspondences to temporal concentration of relative throughfall at our site may be a function of heavy Tillandsia usneoides coverage. Applications of MCA within other forests may provide useful insights to how temporal throughfall dynamics are affected for drainage pathways dependent on different structures (leaves, twigs, branches, etc.).

  4. Walk Ratio (Step Length/Cadence) as a Summary Index of Neuromotor Control of Gait: Application to Multiple Sclerosis

    ERIC Educational Resources Information Center

    Rota, Viviana; Perucca, Laura; Simone, Anna; Tesio, Luigi

    2011-01-01

    In healthy adults, the step length/cadence ratio [walk ratio (WR) in mm/(steps/min) and normalized for height] is known to be constant around 6.5 mm/(step/min). It is a speed-independent index of the overall neuromotor gait control, in as much as it reflects energy expenditure, balance, between-step variability, and attentional demand. The speed…

  5. Genomic architecture of inflammatory bowel disease in five families with multiple affected individuals

    PubMed Central

    Stittrich, Anna B; Ashworth, Justin; Shi, Mude; Robinson, Max; Mauldin, Denise; Brunkow, Mary E; Biswas, Shameek; Kim, Jin-Man; Kwon, Ki-Sun; Jung, Jae U; Galas, David; Serikawa, Kyle; Duerr, Richard H; Guthery, Stephen L; Peschon, Jacques; Hood, Leroy; Roach, Jared C; Glusman, Gustavo

    2016-01-01

    Currently, the best clinical predictor for inflammatory bowel disease (IBD) is family history. Over 163 sequence variants have been associated with IBD in genome-wide association studies, but they have weak effects and explain only a fraction of the observed heritability. It is expected that additional variants contribute to the genomic architecture of IBD, possibly including rare variants with effect sizes larger than the identified common variants. Here we applied a family study design and sequenced 38 individuals from five families, under the hypothesis that families with multiple IBD-affected individuals harbor one or more risk variants that (i) are shared among affected family members, (ii) are rare and (iii) have substantial effect on disease development. Our analysis revealed not only novel candidate risk variants but also high polygenic risk scores for common known risk variants in four out of the five families. Functional analysis of our top novel variant in the remaining family, a rare missense mutation in the ubiquitin ligase TRIM11, suggests that it leads to increased nuclear factor of kappa light chain enhancer in B-cells (NF-κB) signaling. We conclude that an accumulation of common weak-effect variants accounts for the high incidence of IBD in most, but not all families we analyzed and that a family study design can identify novel rare variants conferring risk for IBD with potentially large effect size, such as the TRIM11 p.H414Y mutation. PMID:27081563

  6. CB1 receptor affects cortical plasticity and response to physiotherapy in multiple sclerosis

    PubMed Central

    Mori, Francesco; Ljoka, Concetta; Nicoletti, Carolina G.; Kusayanagi, Hajime; Buttari, Fabio; Giordani, Laura; Rossi, Silvia; Foti, Calogero

    2014-01-01

    Objectives: Therapeutic effects of physical therapy in neurologic disorders mostly rely on the promotion of use-dependent synaptic plasticity in damaged neuronal circuits. Genetic differences affecting the efficiency of synaptic plasticity mechanisms could explain why some patients do not respond adequately to the treatment. It is known that physical exercise activates the endocannabinoid system and that stimulation of cannabinoid CB1 receptors (CB1Rs) promotes synaptic plasticity in both rodents and humans. We thus tested whether CB1R genetic variants affect responsiveness to exercise therapy. Methods: We evaluated the effect of a genetic variant of the CB1R associated with reduced receptor expression (patients with long AAT trinucleotide short tandem repeats in the CNR1 gene) on long-term potentiation (LTP)–like cortical plasticity induced by transcranial magnetic theta burst stimulation (TBS) of the motor cortex and, in parallel, on clinical response to exercise therapy in patients with multiple sclerosis. Results: We found that patients with long AAT CNR1 repeats do not express TBS-induced LTP-like cortical plasticity and show poor clinical benefit after exercise therapy. Conclusions: Our results provide the first evidence that genetic differences within the CB1R may influence clinical responses to exercise therapy, and they strengthen the hypothesis that CB1Rs are involved in the regulation of synaptic plasticity and in the control of spasticity in humans. This information might be of great relevance for patient stratification and personalized rehabilitation treatment programs. PMID:25520956

  7. Do Physical Therapy Interventions Affect Urinary Incontinence and Quality of Life in People with Multiple Sclerosis?

    PubMed Central

    Rivera, Monica; Melnick, Marsha; Allen, Diane D.

    2015-01-01

    Background: Multiple sclerosis (MS) presents with many debilitating symptoms, including urinary incontinence (UI), that physical therapy (PT) may address; UI is widely prevalent, but PT management of symptoms lacks consensus. A meta-analysis of long-term nonsurgical and nonpharmaceutical treatment options may supply this deficiency. We analyzed the current evidence for effectiveness of PT to decrease UI and improve quality of life (QOL) in people with MS. Methods: An electronic search conducted through November 26, 2013, included the following search terms: incontinence, bladder dysfunction, urinary incontinence, multiple sclerosis, MS, physical therapy, physiotherapy, therapy, and rehabilitation. Criteria for inclusion were as follows: MS diagnosis, intervention involved PT for UI or bladder dysfunction, outcomes assessed QOL or UI, and at least a 4 of 10 on the Physiotherapy Evidence Database scale or a 2b level of evidence. Outcomes were combined across studies, and effect sizes are depicted in forest plots. Results: Six studies met the inclusion criteria. Between-group analysis revealed statistically significant differences in incontinence episodes and QOL, but did not reach significance for functional control mechanisms (eg, electromyography data on strength of contraction, relaxation, and endurance). Incontinence leakage episodes and QOL participation improved within groups. Conclusions: Meta-analysis indicates support for PT for minimizing incontinence compared with pretreatment and affecting incontinence and QOL more than control in people with MS. Protocols were heterogeneous regarding duration and type of PT intervention and were applied in different types of MS. Further research may reveal the most effective combination and variety of PT interventions for people with MS. PMID:26300703

  8. Do You Know What I Feel? A First Step towards a Physiological Measure of the Subjective Well-Being of Persons with Profound Intellectual and Multiple Disabilities

    ERIC Educational Resources Information Center

    Vos, Pieter; De Cock, Paul; Petry, Katja; Van Den Noortgate, Wim; Maes, Bea

    2010-01-01

    Background: Because of limited communicative skills, it is not self-evident to measure subjective well-being in people with profound intellectual and multiple disabilities. As a first step towards a non-interpretive measure of subjective well-being, we explored how the respiratory, cardiovascular and electro dermal response systems were associated…

  9. Multiple Landscape Factors Affect the Resilience of a Mixed Land Cover Watershed

    NASA Astrophysics Data System (ADS)

    Golden, H. E.; Lane, C.; Prues, A. G.; D'Amico, E.

    2015-12-01

    Human activities can stimulate the physical and chemical properties of streams to move beyond their background conditions, thereby facilitating the transition of these factors to stressors that affect watershed resilience. This is particularly true in mixed land cover watersheds. We quantify and explore the statistical nonlinear relationships between watershed and buffer-scale factors and nutrient (nitrite-nitrate (NO2-NO3), total Kjeldahl nitrogen (TKN), total phosphorus (TP)) concentrations, in addition to a multi-metric Index of Biotic Integrity (IBI), in a mesoscale mixed land cover watershed. Our goal is to contribute to a better understanding of the potentially numerous landscape and near-stream hydrological and biogeochemical factors that affect watershed resiliency - as inferred from in-stream nutrient levels and biological condition. We used a boosted regression tree approach, which quantifies nonlinear relationships and variable interactions, to develop watershed and 200 m buffer scale models for each chemical constituent and the annual IBI score. We developed nutrient models for the spring and summer seasons. Two primary factors - location within the watershed and percentage of urban land cover in the watershed or buffer - emerged as important explanatory variables in most nutrient and IBI models. Geographic location (i.e., latitude and longitude) interacted with other factors to explain the variability in summer NO2-NO3 concentrations and IBI scores and suggested that location might be associated with indicators of sources (e.g., land cover) and runoff potential (e.g., soil and topographic factors). Runoff indicators (e.g., Hydrologic Soil Group D and Topographic Wetness Indices) explained a substantial portion of the variability in nutrient concentrations as did point sources for TP in the summer months. Our overall approach confirms that it is important to consider multiple and often interacting factors when managing for watershed resilience.

  10. Pseudobulbar affect in multiple sclerosis: toward the development of innovative therapeutic strategies.

    PubMed

    Miller, Ariel

    2006-06-15

    Pseudobulbar affect (PBA), a condition involving involuntary and uncontrollable episodes of crying and/or laughing, occurs frequently in patients with a variety of neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, dementia including Alzheimer's disease, and multiple sclerosis (MS). Although PBA results in considerable distress for patients and caretakers, it is underrecognized and undertreated. Agents used to treat psychiatric disorders--particularly tricyclic antidepressants and selective serotonin reuptake inhibitors--are useful in alleviating PBA, but act on diffuse neural networks rather than targeting those involved in emotional motor expression. As a result of their nonspecific activity, these agents are associated with a range of unwanted effects that preclude many patients from using them. Dextromethorphan, a common cough suppressant, specifically targets sigma(1) receptors concentrated in the brainstem and cerebellum, thus providing the possibility of targeting regions implicated in emotional expression. When administered in a fixed combination with quinidine, dextromethorphan is effective in treating PBA in patients with ALS, and preliminary results suggest that this therapy also is effective in treating MS-related PBA. PMID:16674978

  11. Benthic macroinvertebrate communities affected by multiple stressors within tidal creeks in northeastern USA harbors

    SciTech Connect

    Papageorgis, C.; Murray, M.; Danis, C.; Yates, L.

    1995-12-31

    Surveys of water quality, substrate quality and benthic macroinvertebrates were conducted in a variety of tidal creeks located in the vicinity of a municipal solid waste landfill prior to the construction of a leachate collection system. In-Situ water quality data indicated high water temperatures and low dissolved oxygen values along with high turbidites. Sediment chemistry data indicated that all sediment within the study area exceed USEPA heavy metal criteria. Grain size and salinity data indicate that the study area lies within the Mesohaline Mud habitat class. Water quality data remained within similar concentrations with respect to indicators of leachate. The benthic macroinvertebrate community was consistently dominated by opportunistic Polychaete and Oligochaete worms. Both Shannon diversity and Rarefaction curves were used to evaluate trends in species diversity over time. The study includes a comparison to data obtained by USEPA R-EMAP monitoring programs. While large scale biomonitoring programs do not focus on small tidal creeks this study provides useful data regarding baseline benthic communities within tidal creeks affected by multiple stressors to include previous exposure and potential exposure to oil spills, continued point and non-point municipal and industrial wastewater discharges and physical stressors such as elevated water temperatures, homogeneous silt/clay substrate, and depressed dissolved oxygen values.

  12. Use of Multiple Correspondence Analysis (MCA) to Identify Interactive Meteorological Conditions Affecting Throughfall

    NASA Astrophysics Data System (ADS)

    Lewis, E. S.

    2015-12-01

    Forest canopy alters rainfall reaching the surface by redistributing it as throughfall. Throughfall is critical to watershed ecological variables (soil moisture, stream water discharge/chemistry, and stormflow pathways) and controlled by canopy structural interactions with meteorological conditions across temporal scales. This work introduces and applies multiple correspondence analyses (MCAs) to a range of meteorological thresholds (median intensity, median absolute deviation (MAD) of intensity, mean wind-driven droplet inclination angle, and MAD of wind speed) for an example throughfall problem: identification of interacting storm conditions corresponding to temporal concentration in relative throughfall beyond the median observation (≥73% of rain). MCA results from the example show that equalling or exceeding rain intensity thresholds (median and MAD) corresponded with temporal concentration of relative throughfall across all storms. Under these intensity conditions, two wind mechanisms produced significant correspondences: (1) high, steady wind-driven droplet inclination angles increased surface wetting; and (2) sporadic winds shook entrained droplets from surfaces. A discussion is provided showing that these example MCA findings agree well with previous work. Meteorological threshold correspondences to temporal concentration of relative throughfall at our site may be a function of heavy T. usneoides coverage. Applications of MCA within other forests may provide useful insights to how temporal throughfall dynamics are affected for drainage pathways dependent on different structures (leaves, twigs, branches, etc.).

  13. Virus Multiplicity of Infection Affects Type I Interferon Subtype Induction Profiles and Interferon-Stimulated Genes

    PubMed Central

    Zaritsky, Luna A.; Bedsaul, Jacquelyn R.

    2015-01-01

    ABSTRACT Type I interferons (IFNs) are induced upon viral infection and important mediators of innate immunity. While there is 1 beta interferon (IFN-β) protein, there are 12 different IFN-α subtypes. It has been reported extensively that different viruses induce distinct patterns of IFN subtypes, but it has not been previously shown how the viral multiplicity of infection (MOI) can affect IFN induction. In this study, we discovered the novel finding that human U937 cells infected with 2 different concentrations of Sendai virus (SeV) induce 2 distinct type I IFN subtype profiles. Cells infected at the lower MOI induced more subtypes than cells infected at the higher MOI. We found that this was due to the extent of signaling through the IFN receptor (IFNAR). The cells infected at the lower viral MOI induced the IFNAR2-dependent IFN-α subtypes 4, 6, 7, 10, and 17, which were not induced in cells infected at higher virus concentrations. IFN-β and IFN-α1, -2, and -8 were induced in an IFNAR-independent manner in cells infected at both virus concentrations. IFN-α5, -14, -16, and -21 were induced in an IFNAR-dependent manner in cells infected at lower virus concentrations and in an IFNAR-independent manner in cells infected at higher virus concentrations. These differences in IFN subtype profiles in the 2 virus concentrations also resulted in distinct interferon-stimulated gene induction. These results present the novel finding that different viral MOIs differentially activate JAK/STAT signaling through the IFNAR, which greatly affects the profile of IFN subtypes that are induced. IMPORTANCE Type I IFNs are pleiotropic cytokines that are instrumental in combating viral diseases. Understanding how the individual subtypes are induced is important in developing strategies to block viral replication. Many studies have reported that different viruses induce distinct type I IFN subtype profiles due to differences in the way viruses are sensed in different cell types

  14. Improved characteristics of ultraviolet AlGaN multiple-quantum-well laser diodes with step-graded quantum barriers close to waveguide layers

    NASA Astrophysics Data System (ADS)

    Cai, Xuefen; Li, Shuping; Kang, Junyong

    2016-09-01

    Ultraviolet AlGaN multiple-quantum-well laser diodes (LDs) with step-graded quantum barriers (QBs) instead of conventional first and last QBs close to waveguide layers are proposed. The characteristics of this type of laser diodes are numerically investigated by using the software PICS3D and it is found that the performances of these LDs are greatly improved. The results indicates that the structure with step-graded QBs exhibits higher output light power, slope efficiency and emission intensity, as well as lower series resistance and threshold current density under the identical condition, compared with conventional LD structure.

  15. Multiple factors affect diversity and abundance of ammonia-oxidizing microorganisms in iron mine soil.

    PubMed

    Xing, Yi; Si, Yan-Xiao; Hong, Chen; Li, Yang

    2015-07-01

    Ammonia oxidation by microorganisms is a critical process in the nitrogen cycle. In this study, four soil samples collected from a desert zone in an iron-exploration area and others from farmland and planted forest soil in an iron mine surrounding area. We analyzed the abundance and diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in iron-mining area near the Miyun reservoir using ammonia monooxygenase. A subunit gene (amoA) as molecular biomarker. Quantitative polymerase chain reaction was applied to explore the relationships between the abundance of AOA and AOB and soil physicochemical parameters. The results showed that AOA were more abundant than AOB and may play a more dominant role in the ammonia-oxidizing process in the whole region. PCR-denaturing gradient gel electrophoresis was used to analyze the structural changes of AOA and AOB. The results showed that AOB were much more diverse than AOA. Nitrosospira cluster three constitute the majority of AOB, and AOA were dominated by group 1.1b in the soil. Redundancy analysis was performed to explore the physicochemical parameters potentially important to AOA and AOB. Soil characteristics (i.e. water, ammonia, organic carbon, total nitrogen, available phosphorus, and soil type) were proposed to potentially contribute to the distributions of AOB, whereas Cd was also closely correlated to the distributions of AOB. The community of AOA correlated with ammonium and water contents. These results highlight the importance of multiple drivers in microbial niche formation as well as their affect on ammonia oxidizer composition, both which have significant consequences for ecosystem nitrogen functioning. PMID:25860433

  16. Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans

    PubMed Central

    Saccone, Nancy L.; Schwantes-An, Tae-Hwi; Wang, Jen C.; Grucza, Richard A.; Breslau, Naomi; Hatsukami, Dorothy; Johnson, Eric O.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2010-01-01

    Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer, and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect risk for nicotine dependence in a new sample of African-Americans (N = 710). We also analyzed this African-American sample together with a European-American sample (N=2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non-dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7, and CHRNA10 show modest association with nicotine dependence risk in the African-American sample. In addition, CHRNA4, CHRNB3-CHRNA6, and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor SNPs that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the African-American sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in European-Americans and also 1.9% in African-Americans; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside of chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations. PMID:20584212

  17. Polymorphisms within beta-catenin encoding gene affect multiple myeloma development and treatment.

    PubMed

    Butrym, Aleksandra; Rybka, Justyna; Łacina, Piotr; Gębura, Katarzyna; Frontkiewicz, Diana; Bogunia-Kubik, Katarzyna; Mazur, Grzegorz

    2015-12-01

    Recent studies have suggested that cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, and that dysregulation of Wnt/β-catenin pathway may be one of possible reasons of lenalidomide resistance. This prompted us to analyze the effect of polymorphisms within the genes coding for cereblon (CRBN (rs121918368 C>T)) and β-catenin (CTNNB1 (rs4135385 A>G; rs4533622 A>C)). MM patients (n=142) and healthy individuals (n=123) were genotyped using the Light SNiP assays. The presence of the CTNNB1 (rs4533622) A allele was more frequently detected in patients presented with stage II-III disease according to International Staging System (63/82 vs. 26/44, p=0.043) and Durie-Salmon criteria (75/99 vs. 14/26, p=0.049). The CTNNB1 (rs4135385) AA homozygosity was more frequent among patients with better response to CTD, i.e., cyclophosphamide-thalidomide-dexamethasone (18/23 vs. 32/60, p=0.047). Patients carrying the CTNNB1 (rs4533622) AA genotype were better responders to the first line therapy with thalidomide containing regimens (p<0.05). No significant association was observed between the effect of lenalidomide therapy and polymorphisms studied. However, the occurrence of neutropenia during lenalidomide therapy was more frequent among the CTNNB1 (rs4135385) AA carriers (p=0.019), while the CTNNB1 (rs4533622) AA homozygosity characterized patients with high grade (3-4) neutropenia (p=0.044). No association was found for the CRBN polymorphism. These results suggest that the CTNNB1 polymorphisms may affect the clinical course and response to chemotherapy in patients with multiple myeloma. PMID:26521987

  18. Parallel fluctuations of psychiatric and neurological symptoms in a patient with multiple sclerosis and bipolar affective disorder.

    PubMed

    Salmaggi, A; Eoli, M; La Mantia, L; Erbetta, A

    1995-11-01

    The case of a female patient affected by simultaneously onsetting multiple sclerosis and bipolar affective disorder at age 33 is reported. Over the following years, the patient displayed minor mood fluctuations but, at the ages of 41 and 42 years, respectively, she suffered from a major depressive and a manic episode, both of which were concomitant with a marked worsening in her neurological condition. PMID:8613416

  19. Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods

    NASA Astrophysics Data System (ADS)

    Kapil, V.; VandeVondele, J.; Ceriotti, M.

    2016-02-01

    The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats.

  20. Physical and Cognitive-Affective Factors Associated with Fatigue in Individuals with Fibromyalgia: A Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Muller, Veronica; Brooks, Jessica; Tu, Wei-Mo; Moser, Erin; Lo, Chu-Ling; Chan, Fong

    2015-01-01

    Purpose: The main objective of this study was to determine the extent to which physical and cognitive-affective factors are associated with fibromyalgia (FM) fatigue. Method: A quantitative descriptive design using correlation techniques and multiple regression analysis. The participants consisted of 302 members of the National Fibromyalgia &…

  1. Distribution and evolution of multiple-step phosphorelay in prokaryotes: lateral domain recruitment involved in the formation of hybrid-type histidine kinases

    SciTech Connect

    Zhang, Weiwen; Shi, Liang

    2005-06-01

    Although most two-component signal transduction systems (TCSTS) use a simple phosphotransfer pathway from one histidine kinase (HK) to one response regulator (RR), a multiple-step phosphorelay involving a phosphotransfer scheme of His-Asp-His-Asp was discovered in recent years. Central to this multiple-step type signal transduction pathway are a hybrid-type HK, containing both an HK kinase domain and a RR receiver domain in a single protein, and a histidine-containing phosphotransfer (HPT) that can exist as either a domain in hybrid-type HKs or as a separate protein. While multiple-step phosphorelay systems predominant in eukaryotes, it has been previously suggested that they are less common in prokaryotes. In this study, we found that putative hybrid-type HKs were present in 56 out of 156 complete prokaryotic genomes, indicating that multiple-step phosphorelay systems are more common in prokaryotes than previously appreciated. Large expansions of hybrid-type HKs were observed in several types of bacterial species, including cyanobacteria, several bacteria involved in bacteria-eukaryote interaction, and metabolically versatile bacteria. Phylogenetic analysis indicated that there was no common ancestor for hybrid-type of HKs, and their origin and expansion was achieved by lateral recruitment of a receiver domain into an HK molecule and then duplication as one unit. Lateral recruitment of additional sensory domains such as PAS was also evident. HPT domains or proteins were identified in 32 of the genomes with hybrid-type HKs, however, no significant gene expansion was observed for HPTs even in genome with large number of hybrid-type HKs. In addition, the observation of fewer HPTs than hybrid-type HKs in almost all genomes studied suggests that there is no simple one-to-one relationship between them

  2. Intermolecular C-H activation with an Ir-METAMORPhos piano-stool complex--multiple reaction steps at a reactive ligand.

    PubMed

    Oldenhof, S; Lutz, M; van der Vlugt, J I; Reek, J N H

    2015-10-21

    Substrate activation by means of a reactive ligand is a topic of much interest. Herein we describe a stoichiometric anti-Markovnikov C-N bond formation involving ligand reactivity in multiple steps along the reaction coordinate, including ligand assisted substrate (de)protonation and C-N bond formation, as illustrated by a combined experimental, spectroscopic and computational study. This affords a highly unusual four-membered iridacycle bearing an exo-cyclic C=C double bond. PMID:26329519

  3. “So We Adapt Step by Step”: Acculturation Experiences Affecting Diabetes Management and Perceived Health for Chinese American Immigrants

    PubMed Central

    Chun, Kevin M.; Chesla, Catherine A.; Kwan, Christine M.L.

    2011-01-01

    This study examines how acculturation affects type 2 diabetes management and perceived health for Chinese American immigrants in the U.S. Acculturation experiences or cultural adaptation experiences affecting diabetes management and health were solicited from an informant group of immigrant patients and their spouses (N=40) during group, couple and individual interviews conducted in 2005 to 2008. A separate respondent group of immigrant patients and their spouses (N=19) meeting inclusion criteria reviewed and confirmed themes generated by the informant group. Using interpretive phenomenology, three key themes in patients’ and spouses’ acculturation experiences were identified: a) utilizing health care, b) maintaining family relations and roles, and c) establishing community ties and groundedness in the U.S. Acculturation experiences reflecting these themes were broad in scope and not fully captured by current self-report and proxy acculturation measures. In the current study, shifting family roles and evaluations of diabetes care and physical environment in the U.S. significantly affected diabetes management and health, yet are overlooked in acculturation and health investigations. Furthermore, the salience and impact of specific acculturation experiences respective to diabetes management and perceived health varied across participants due to individual, family, developmental, and environmental factors. In regards to salience, maintaining filial and interdependent family relations in the U.S. was of particular concern for older participants and coping with inadequate health insurance in the U.S. was especially distressing for self-described lower-middle to middle-class participants. In terms of impact, family separation and relocating to ethnically similar neighborhoods in the U.S. differentially affected diabetes management and health due to participants’ varied family relations and pre-migration family support levels and diverse cultural and linguistic

  4. von Hippel–Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

    PubMed Central

    Mousnier, Aurélie; Kubat, Nicole; Massias-Simon, Aurélie; Ségéral, Emmanuel; Rain, Jean-Christophe; Benarous, Richard; Emiliani, Stéphane; Dargemont, Catherine

    2007-01-01

    HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin–proteasome pathway. Here, we identify von Hippel–Lindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel–Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin–VHL–proteasome pathway in the integration–transcription transition of the viral replication cycle. PMID:17698809

  5. Multiple Perspectives in a Rock: How Physical Geography Is Affected by Human Perceptions.

    ERIC Educational Resources Information Center

    Obenchain, Kathryn M.

    2000-01-01

    Discusses the importance of teaching geography, focusing on the multiple perspectives associated with a physical place. Provides suggestions for exploring these perspectives at the primary, intermediate, and high school levels in a geography-centered social studies classroom. (CMK)

  6. Integration Strategy Is a Key Step in Network-Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes

    PubMed Central

    Jin, Nana; Wu, Deng; Gong, Yonghui; Bi, Xiaoman; Jiang, Hong; Li, Kongning; Wang, Qianghu

    2014-01-01

    An increasing number of experiments have been designed to detect intracellular and intercellular molecular interactions. Based on these molecular interactions (especially protein interactions), molecular networks have been built for using in several typical applications, such as the discovery of new disease genes and the identification of drug targets and molecular complexes. Because the data are incomplete and a considerable number of false-positive interactions exist, protein interactions from different sources are commonly integrated in network analyses to build a stable molecular network. Although various types of integration strategies are being applied in current studies, the topological properties of the networks from these different integration strategies, especially typical applications based on these network integration strategies, have not been rigorously evaluated. In this paper, systematic analyses were performed to evaluate 11 frequently used methods using two types of integration strategies: empirical and machine learning methods. The topological properties of the networks of these different integration strategies were found to significantly differ. Moreover, these networks were found to dramatically affect the outcomes of typical applications, such as disease gene predictions, drug target detections, and molecular complex identifications. The analysis presented in this paper could provide an important basis for future network-based biological researches. PMID:25243127

  7. Features of polarization decay in the transition between the low-step and multiple scattering of laser light

    NASA Astrophysics Data System (ADS)

    Zimnyakov, D. A.; Yuvchenko, S. A.; Taskina, L. A.; Alonova, M. V.; Isaeva, E. A.; Isaeva, A. A.; Ushakova, O. V.

    2016-04-01

    The effect of increase in the uncertainty of local polarization states of laser light forward scattered by random media was studied in the experiments with phantom scatterers. At macroscopic level this effect is related to decay in the degree of polarization of scattered light in the course of transition from single to multiple scattering. Gelatin layers with embedded titania particles were used as the phantom scatterers. Features of distributions of local polarization states in various polarization coordinates were considered.

  8. Multiple time courses of salivary alpha-amylase and dimensions of affect in adolescence.

    PubMed

    Doane, Leah D; Van Lenten, Scott A

    2014-11-01

    Previous research has illustrated associations among daily experiences, emotions and stress-responding physiological systems. Recently, investigators have examined salivary alpha-amylase (sAA), a surrogate marker of the autonomic nervous system, and its associations with affect. The current study examined associations among affective valence, arousal and sAA across three different time courses at the momentary, daily and inter-individual level to understand varying influences of adolescents' daily emotional experiences on sAA reactivity and diurnal sAA activity. Adolescents (N=82) provided salivary samples and diary reports of affect and experiences five times a day for three consecutive days. They also completed self-report questionnaires on trait affect. Findings from multilevel growth curves demonstrated that adolescents in our sample displayed typical sAA diurnal rhythms with levels dropping 30 min after waking and then increasing across the day to a peak in the late afternoon. Within person momentary experiences of high arousal positive affect were associated with momentary sAA reactivity. Prior day experiences of high arousal negative affect were associated with a greater amylase awakening response (i.e., greater decrease) and flatter slopes the next day. Trait positive affect was also associated with flatter sAA slopes. Our findings suggest that both affective arousal and valence should be accounted for when examining differences in sAA reactivity and diurnal patterns. Further, our results indicated that emotion-physiology transactions among adolescents occur over varying time scales for salivary alpha-amylase as well as cortisol. PMID:25076484

  9. A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis

    PubMed Central

    Carulli, Christian; Nistri, Lorenzo; Bracco, Laura; Giannini, Marta; Amato, Maria Pia

    2015-01-01

    Summary Patients affected by Multiple Sclerosis are often treated by pulsed intravenous corticosteroids to manage acute relapses with positive outcomes. The intravenous administration is frequently associated to avascular necrosis of several bones, particularly the femur. The present report regards a case of an underage MS patient with a bilateral ANFH secondary to pulsed administrations of steroids, managed by a conservative approach on a hip, and by a novel surgical technique on the contralateral side. PMID:26811707

  10. A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis.

    PubMed

    Carulli, Christian; Nistri, Lorenzo; Bracco, Laura; Giannini, Marta; Amato, Maria Pia

    2015-01-01

    Patients affected by Multiple Sclerosis are often treated by pulsed intravenous corticosteroids to manage acute relapses with positive outcomes. The intravenous administration is frequently associated to avascular necrosis of several bones, particularly the femur. The present report regards a case of an underage MS patient with a bilateral ANFH secondary to pulsed administrations of steroids, managed by a conservative approach on a hip, and by a novel surgical technique on the contralateral side. PMID:26811707

  11. Characterizing multiple timescales of stream and storage zone interaction that affect solute fate and transport in streams

    USGS Publications Warehouse

    Choi, J.; Harvey, J.W.; Conklin, M.H.

    2000-01-01

    The fate of contaminants in streams and rivers is affected by exchange and biogeochemical transformation in slowly moving or stagnant flow zones that interact with rapid flow in the main channel. In a typical stream, there are multiple types of slowly moving flow zones in which exchange and transformation occur, such as stagnant or recirculating surface water as well as subsurface hyporheic zones. However, most investigators use transport models with just a single storage zone in their modeling studies, which assumes that the effects of multiple storage zones can be lumped together. Our study addressed the following question: Can a single-storage zone model reliably characterize the effects of physical retention and biogeochemical reactions in multiple storage zones? We extended an existing stream transport model with a single storage zone to include a second storage zone. With the extended model we generated 500 data sets representing transport of nonreactive and reactive solutes in stream systems that have two different types of storage zones with variable hydrologic conditions. The one storage zone model was tested by optimizing the lumped storage parameters to achieve a best fit for each of the generated data sets. Multiple storage processes were categorized as possessing I, additive; II, competitive; or III, dominant storage zone characteristics. The classification was based on the goodness of fit of generated data sets, the degree of similarity in mean retention time of the two storage zones, and the relative distributions of exchange flux and storage capacity between the two storage zones. For most cases (> 90%) the one storage zone model described either the effect of the sum of multiple storage processes (category I) or the dominant storage process (category III). Failure of the one storage zone model occurred mainly for category II, that is, when one of the storage zones had a much longer mean retention time (t(s) ratio > 5.0) and when the dominance of

  12. The Membrane Fusion Step of Vaccinia Virus Entry Is Cooperatively Mediated by Multiple Viral Proteins and Host Cell Components

    PubMed Central

    Laliberte, Jason P.; Weisberg, Andrea S.; Moss, Bernard

    2011-01-01

    For many viruses, one or two proteins allow cell attachment and entry, which occurs through the plasma membrane or following endocytosis at low pH. In contrast, vaccinia virus (VACV) enters cells by both neutral and low pH routes; four proteins mediate cell attachment and twelve that are associated in a membrane complex and conserved in all poxviruses are dedicated to entry. The aim of the present study was to determine the roles of cellular and viral proteins in initial stages of entry, specifically fusion of the membranes of the mature virion and cell. For analysis of the role of cellular components, we used well characterized inhibitors and measured binding of a recombinant VACV virion containing Gaussia luciferase fused to a core protein; viral and cellular membrane lipid mixing with a self-quenching fluorescent probe in the virion membrane; and core entry with a recombinant VACV expressing firefly luciferase and electron microscopy. We determined that inhibitors of tyrosine protein kinases, dynamin GTPase and actin dynamics had little effect on binding of virions to cells but impaired membrane fusion, whereas partial cholesterol depletion and inhibitors of endosomal acidification and membrane blebbing had a severe effect at the later stage of core entry. To determine the role of viral proteins, virions lacking individual membrane components were purified from cells infected with members of a panel of ten conditional-lethal inducible mutants. Each of the entry protein-deficient virions had severely reduced infectivity and except for A28, L1 and L5 greatly impaired membrane fusion. In addition, a potent neutralizing L1 monoclonal antibody blocked entry at a post-membrane lipid-mixing step. Taken together, these results suggested a 2-step entry model and implicated an unprecedented number of viral proteins and cellular components involved in signaling and actin rearrangement for initiation of virus-cell membrane fusion during poxvirus entry. PMID:22194690

  13. Stochastic analysis of multiple-passband spectral classifications systems affected by observation errors

    NASA Technical Reports Server (NTRS)

    Tsokos, C. P.

    1980-01-01

    The classification of targets viewed by a pushbroom type multiple band spectral scanner by algorithms suitable for implementation in high speed online digital circuits is considered. A class of algorithms suitable for use with a pipelined classifier is investigated through simulations based on observed data from agricultural targets. It is shown that time distribution of target types is an important determining factor in classification efficiency.

  14. Decision Aids for Multiple-Decision Disease Management as Affected by Weather Input Errors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many disease management decision support systems (DSS) rely, exclusively or in part, on weather inputs to calculate an indicator for disease hazard. Error in the weather inputs, typically due to forecasting, interpolation or estimation from off-site sources, may affect model calculations and manage...

  15. An Analysis of Multiple Factors Affecting Retention in Web-Based Community College Courses

    ERIC Educational Resources Information Center

    Doherty, William

    2006-01-01

    The current study examined four factors affecting retention in Web-based community college courses. Analyses were conducted on student demographics, student learning styles, course communication and external factors. The results suggest that Web-based courses are more attractive to busy students who are also more likely to fail or drop the course.…

  16. How Single or Multiple Pitch Labels Affect Young Children's Identification of Pitch.

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia; Descombes, Valerie

    1997-01-01

    Examines whether the consistent or inconsistent use of pitch labels during instruction in pitch terminology affected French kindergarten children's identification of pitch in the two chosen classes. Finds that the children who were taught one pair of terms provided significantly more correct verbal responses than did the group who learned two…

  17. Factors Affecting University Entrants' Performance in High-Stakes Tests: A Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Uy, Chin; Manalo, Ronaldo A.; Cabauatan, Ronaldo R.

    2015-01-01

    In the Philippines, students seeking admission to a university are usually required to meet certain entrance requirements, including passing the entrance examinations with questions on IQ and English, mathematics, and science. This paper aims to determine the factors that affect the performance of entrants into business programmes in high-stakes…

  18. Severe acute respiratory syndrome coronavirus protein nsp1 is a novel eukaryotic translation inhibitor that represses multiple steps of translation initiation.

    PubMed

    Lokugamage, Kumari G; Narayanan, Krishna; Huang, Cheng; Makino, Shinji

    2012-12-01

    Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template. PMID:23035226

  19. Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage.

    PubMed Central

    Anderson, E D; VanSlyke, J K; Thulin, C D; Jean, F; Thomas, G

    1997-01-01

    Activation of furin requires autoproteolytic cleavage of its 83-amino acid propeptide at the consensus furin site, Arg-Thr-Lys-Arg107/. This RER-localized cleavage is necessary, but not sufficient, for enzyme activation. Rather, full activation of furin requires exposure to, and correct routing within, the TGN/endosomal system. Here, we identify the steps in addition to the initial propeptide cleavage necessary for activation of furin. Exposure of membrane preparations containing an inactive RER-localized soluble furin construct to either: (i) an acidic and calcium-containing environment characteristic of the TGN; or (ii) mild trypsinization at neutral pH, resulted in the activation of the endoprotease. Taken together, these results suggest that the pH drop facilitates the removal of a furin inhibitor. Consistent with these findings, following cleavage in the RER, the furin propeptide remains associated with the enzyme and functions as a potent inhibitor of the endoprotease. Co-immunoprecipitation studies coupled with analysis by mass spectrometry show that release of the propeptide at acidic pH, and hence activation of furin, requires a second cleavage within the autoinhibitory domain at a site containing a P6 arginine (-Arg70-Gly-Val-Thr-Lys-Arg75/-). The significance of this cleavage in regulating the compartment-specific activation of furin, and the relationship of the furin activation pathway to those of other serine endoproteases are discussed. PMID:9130696

  20. Multiple Nonthermal Reaction Steps for the Photooxidation of CO to CO2 on Reduced TiO2(110).

    PubMed

    Petrik, Nikolay G; Kimmel, Greg A

    2013-02-01

    The photooxidation of CO on reduced, rutile TiO2(110) is studied on a millisecond time scale. For CO coadsorbed with a saturation coverage of chemisorbed O2 (θsat), the CO2 photon-stimulated desorption (PSD) signal is initially zero, increases to a maximum after several tens of milliseconds, and then decreases at longer times. The initial CO2 PSD signal increases ∼5 times more quickly for an oxygen coverage of 0.5θsat. The initial rate of increase of the CO2 PSD signal is proportional to the flux of UV photons. The results show that two or more nonthermal reaction steps are required to photooxidize CO adsorbed on TiO2(110). The intermediate species involved in the reactions is stable for at least 100 s at 30 K. Previous models had suggested that CO photooxidation required only one nonthermal reaction. The likely initial and final charge states of the system suggest that an electron-mediated reaction and a hole-mediated reaction are needed for the complete photooxidation reaction. PMID:26281721

  1. Pain affects depression through anxiety, fatigue and sleep in Multiple Sclerosis

    PubMed Central

    Amtmann, Dagmar; Askew, Robert L.; Kim, Jiseon; Chung, Hyewon; Ehde, Dawn M.; Bombardier, Charles H.; Kraft, George H.; Jones, Salene M.; Johnson, Kurt L.

    2015-01-01

    Objective Over a quarter million individuals in the US have Multiple Sclerosis (MS). Chronic pain and depression are disproportionately high in this population. The purpose of this study was to examine the relationship between chronic pain and depression in MS and to examine potentially meditational effects of anxiety, fatigue and sleep. Methods Cross-sectional data from self-reported instruments measuring multiple symptoms and quality of life indicators were used in this study. Structural equation modeling (SEM) was utilized to model direct and indirect effects of pain on depression in a sample of 1245 community dwelling individuals with MS. Pain interference, depression, fatigue and sleep disturbance were modeled as latent variables with 2 to 3 indicators each. The model controlled for age, sex, disability status (EDSS) and social support. Results A model with indirect effects of pain on depression had adequate fit and accounted for nearly 80% of the variance in depression. The effects of chronic pain on depression were almost completely mediated by fatigue, anxiety, and sleep disturbance. Higher pain was associated with greater fatigue, anxiety, and sleep disturbance, which in turn were associated with higher levels of depression. The largest mediating effect was through fatigue. Additional analyses excluded items with common content and suggested that the meditational effects observed were not attributable to content overlap across scales. Conclusions Individuals living with MS who report high levels of chronic pain and depressive symptoms may benefit from treatment approaches that can address sleep, fatigue, and anxiety. PMID:25602361

  2. Increasing Access to Clinical Trials and Innovative Therapy for Teenagers and Young Adults with Cancer - A Multiple Stakeholders and Multiple Steps Process.

    PubMed

    Gaspar, Nathalie; Fern, Lorna

    2016-01-01

    The inclusion of teenagers and young adults (TYAs) in cancer clinical trials is focal point for many countries with a specific TYA program. This objective has arisen from data which suggests that lower trial entry may, in part, contribute to lesser survival gains observed in this group when compared to children and some older adult cancers. In this chapter, we discuss obstacles to clinical trials and innovative therapies for TYA. Limited clinical trial availability is discussed in the context of the rarity of TYA cancers and our limited understanding of cancer biology in this group, other obstacles include inappropriate age eligibility criteria, limited accessibility to available trials, a lack of physicians and patients awareness and poor acceptability of trial design. We propose several strategies which could be applied to overcome these obstacles, some ready for implementation and others which require further exploration. Strengthening pediatric and adult oncology collaboration at the individual level and through oncology societies will undoubtedly positively impact accrual to trials for TYA, as will abolishing the use of age as a barrier to drug and trial access. This will allow us to create biologically driven trials and facilitate early new drug access and the creation of biobank collections to drive our understanding of the biology of cancers in this age group. Involving multiple stakeholders in trial design will facilitate acceptable trials to both healthcare professionals and young people themselves. The support of the multidisciplinary TYA team and a culture of research embedded within this are the keys to improving access and participation of TYA in cancer trials. PMID:27595355

  3. Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods.

    PubMed

    Kapil, V; VandeVondele, J; Ceriotti, M

    2016-02-01

    The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats. PMID:26851912

  4. Relationships Among Depressive Symptoms, Benefit-Finding, Optimism, and Positive Affect in Multiple Sclerosis Patients After Psychotherapy for Depression

    PubMed Central

    Hart, Stacey L.; Vella, Lea; Mohr, David C.

    2013-01-01

    Objective While many patients with multiple sclerosis (MS) experience psychological problems, such as depression, benefit-finding is commonly reported. Using the Broaden-and-Build Model of positive emotions (Fredrickson, 2001) and the Expectancy-Value Model of optimism (Carver & Scheier, 1998) as two related, yet, distinct conceptual frameworks, this study examined positive affect and optimism as mediators of the relationship between improved depression and enhanced benefit-finding. Design MS patients (N = 127), who participated in a larger, randomized clinical trial comparing two types of telephone psychotherapy for depression, were assessed at baseline, midtherapy (8 weeks), end of therapy (16 weeks), and 6- and 12-month posttherapy. Main Outcome Measures Depression was measured with a telephone administered version of the Hamilton Rating Scale for Depression; Positive Affect was measured with the Positive Affect Subscale from the Positive and Negative Affect Scale; Optimism was measured with the Life Orientation Test—Revised; Benefit-Finding was measured with the revised version of the Stress-Related Growth Scale. Results Data were analyzed with multilevel random-effects models, controlling for time since MS diagnosis and type of treatment. Improved depression was associated with increased benefit-finding over time. The relationship between improved depression and benefit-finding was significantly mediated by both increased optimism and increased positive affect. Conclusion Findings provide support to both theoretical models. Positivity appears to promote benefit-finding in MS. PMID:18377142

  5. Self-Reported Trait Mindfulness and Affective Reactivity: A Motivational Approach Using Multiple Psychophysiological Measures

    PubMed Central

    Cosme, Danielle; Wiens, Stefan

    2015-01-01

    As a form of attention, mindfulness is qualitatively receptive and non-reactive, and is thought to facilitate adaptive emotional responding. One suggested mechanism is that mindfulness facilitates disengagement from an affective stimulus and thereby decreases affective reactivity. However, mindfulness has been conceptualized as a state, intervention, and trait. Because evidence is mixed as to whether self-reported trait mindfulness decreases affective reactivity, we used a multi-method approach to study the relationship between individual differences in self-reported trait mindfulness and electrocortical, electrodermal, electromyographic, and self-reported responses to emotional pictures. Specifically, while participants (N = 51) passively viewed pleasant, neutral, and unpleasant IAPS pictures, we recorded high-density (128 channels) electrocortical, electrodermal, and electromyographic data to the pictures as well as to acoustic startle probes presented during the pictures. Afterwards, participants rated their subjective valence and arousal while viewing the pictures again. If trait mindfulness spontaneously reduces general emotional reactivity, then for individuals reporting high rather than low mindfulness, response differences between emotional and neutral pictures would show relatively decreased early posterior negativity (EPN) and late positive potential (LPP) amplitudes, decreased skin conductance responses, and decreased subjective ratings for valence and arousal. High mindfulness would also be associated with decreased emotional modulation of startle eyeblink and P3 amplitudes. Although results showed clear effects of emotion on the dependent measures, in general, mindfulness did not moderate these effects. For most measures, effect sizes were small with rather narrow confidence intervals. These data do not support the hypothesis that individual differences in self-reported trait mindfulness are related to spontaneous emotional responses during picture

  6. Self-reported trait mindfulness and affective reactivity: a motivational approach using multiple psychophysiological measures.

    PubMed

    Cosme, Danielle; Wiens, Stefan

    2015-01-01

    As a form of attention, mindfulness is qualitatively receptive and non-reactive, and is thought to facilitate adaptive emotional responding. One suggested mechanism is that mindfulness facilitates disengagement from an affective stimulus and thereby decreases affective reactivity. However, mindfulness has been conceptualized as a state, intervention, and trait. Because evidence is mixed as to whether self-reported trait mindfulness decreases affective reactivity, we used a multi-method approach to study the relationship between individual differences in self-reported trait mindfulness and electrocortical, electrodermal, electromyographic, and self-reported responses to emotional pictures. Specifically, while participants (N = 51) passively viewed pleasant, neutral, and unpleasant IAPS pictures, we recorded high-density (128 channels) electrocortical, electrodermal, and electromyographic data to the pictures as well as to acoustic startle probes presented during the pictures. Afterwards, participants rated their subjective valence and arousal while viewing the pictures again. If trait mindfulness spontaneously reduces general emotional reactivity, then for individuals reporting high rather than low mindfulness, response differences between emotional and neutral pictures would show relatively decreased early posterior negativity (EPN) and late positive potential (LPP) amplitudes, decreased skin conductance responses, and decreased subjective ratings for valence and arousal. High mindfulness would also be associated with decreased emotional modulation of startle eyeblink and P3 amplitudes. Although results showed clear effects of emotion on the dependent measures, in general, mindfulness did not moderate these effects. For most measures, effect sizes were small with rather narrow confidence intervals. These data do not support the hypothesis that individual differences in self-reported trait mindfulness are related to spontaneous emotional responses during picture

  7. Real-time tests of multiple genome alterations take the first steps into the clinic: a learning example

    PubMed Central

    Gerratana, Lorenzo; De Maglio, Giovanna; De Pellegrin, Alessandro; Follador, Alessandro; Rihawi, Karim; Pizzolitto, Stefano; Puglisi, Fabio; Fasola, Gianpiero

    2016-01-01

    Molecular characterization is increasingly changing clinical practice, in both diagnosis and treatment. BRAF is a proto-oncogene that is mutated in ~2%–4% of lung cancers, but the incidence rises to 40%–45% among papillary thyroid cancers. Furthermore, BRAF is a promising target in lung cancer treatment. The present case study covers both the challenges of molecular differential diagnosis and the perspectives opened by targeted therapy by discussing the history of a 78-year-old female affected by a papillary histotype carcinoma with BRAF mutation associated with both thyroid and lung localizations. A differential diagnosis was possible as a consequence of a multidisciplinary approach including an in-depth molecular characterization. Based on this molecular feature, the patient was successfully treated with the BRAF inhibitor dabrafenib after the failure of treatment with standard regimen. To the best of our knowledge, this is the first published case of non-small-cell lung cancer with metastasis to thyroid and with BRAF V600E mutation.

  8. Real-time tests of multiple genome alterations take the first steps into the clinic: a learning example.

    PubMed

    Gerratana, Lorenzo; De Maglio, Giovanna; De Pellegrin, Alessandro; Follador, Alessandro; Rihawi, Karim; Pizzolitto, Stefano; Puglisi, Fabio; Fasola, Gianpiero

    2016-01-01

    Molecular characterization is increasingly changing clinical practice, in both diagnosis and treatment. BRAF is a proto-oncogene that is mutated in ~2%-4% of lung cancers, but the incidence rises to 40%-45% among papillary thyroid cancers. Furthermore, BRAF is a promising target in lung cancer treatment. The present case study covers both the challenges of molecular differential diagnosis and the perspectives opened by targeted therapy by discussing the history of a 78-year-old female affected by a papillary histotype carcinoma with BRAF mutation associated with both thyroid and lung localizations. A differential diagnosis was possible as a consequence of a multidisciplinary approach including an in-depth molecular characterization. Based on this molecular feature, the patient was successfully treated with the BRAF inhibitor dabrafenib after the failure of treatment with standard regimen. To the best of our knowledge, this is the first published case of non-small-cell lung cancer with metastasis to thyroid and with BRAF V600E mutation. PMID:27621653

  9. Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development.

    PubMed

    Mangiavini, Laura; Merceron, Christophe; Araldi, Elisa; Khatri, Richa; Gerard-O'Riley, Rita; Wilson, Tremika LeShan; Rankin, Erinn B; Giaccia, Amato J; Schipani, Ernestina

    2014-09-01

    Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements. PMID:24972088

  10. Implementing the ten steps to successful breastfeeding in multiple hospitals serving low-wealth patients in the US: innovative research design and baseline findings

    PubMed Central

    2013-01-01

    Background The Ten Steps to Successful Breastfeeding are maternity practices proven to support successful achievement of exclusive breastfeeding. They also are the basis for the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). This study explores implementation of these steps in hospitals that serve predominantly low wealth populations. Methods A quasi-experimental design with mixed methods for data collection and analysis was included within an intervention project. We compared the impact of a modified Ten Steps implementation approach to a control group. The intervention was carried out in hospitals where: 1) BFHI designation was not necessarily under consideration, and 2) the majority of the patient population was low wealth, i.e., eligible for Medicaid. Hospitals in the research aspect of this project were systematically assigned to one of two groups: Initial Intervention or Initial Control/Later Intervention. This paper includes analyses from the baseline data collection, which consisted of an eSurvey (i.e., Carolina B-KAP), Maternity Practices in Infant Nutrition and Care survey tool (mPINC), the BFHI Self-Appraisal, key informant interviews, breastfeeding data, and formatted feedback discussion. Results Comparability was ensured by statistical and non-parametric tests of baseline characteristics of the two groups. Additional findings of interest included: 1) a universal lack of consistent breastfeeding records and statistics for regular monitoring/review, 2) widespread misinterpretation of associated terminology, 3) health care providers’ reported practices not necessarily reflective of their knowledge and attitudes, and 4) specific steps were found to be associated with hospital breastfeeding rates. A comprehensive set of facilitators and obstacles to initiation of the Ten Steps emerged, and hospital-specific practice change challenges were identified. Discussion This is one of the first studies to examine introduction of the Ten Steps in multiple

  11. Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Modifies T Cells at Multiple Steps and Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis1

    PubMed Central

    Brahmachari, Saurav; Pahan, Kalipada

    2007-01-01

    Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. This study explores a novel use of sodium benzoate (NaB), a commonly used food additive and a Food and Drug Administration-approved nontoxic drug for urea cycle disorders, in treating the disease process of relapsing-remitting EAE in female SJL/J mice. NaB, administered through drinking water at physiologically tolerable doses, ameliorated clinical symptoms and disease progression of EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. Histological studies reveal that NaB effectively inhibited infiltration of mononuclear cells and demyelination in the spinal cord of EAE mice. Consequently, NaB also suppressed the expression of proinflammatory molecules and normalized myelin gene expression in the CNS of EAE mice. Furthermore, we observed that NaB switched the differentiation of myelin basic protein-primed T cells from Th1 to Th2 mode, enriched regulatory T cell population, and down-regulated the expression of various contact molecules in T cells. Taken together, our results suggest that NaB modifies encephalitogenic T cells at multiple steps and that NaB may have therapeutic importance in multiple sclerosis. PMID:17579047

  12. Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV Reactivation

    PubMed Central

    Bellizzi, Anna; Morreale, Manuela; Pontecorvo, Simona; D’Abramo, Alessandra; Oliva, Alessandra; Anzivino, Elena; Lo Menzo, Sara; D’Agostino, Claudia; Mastroianni, Claudio Maria; Millefiorini, Enrico; Pietropaolo, Valeria; Francia, Ada; Vullo, Vincenzo; Ciardi, Maria Rosa

    2016-01-01

    The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects. PMID:27486658

  13. An unequivocal example of cysteine proteinase activity affected by multiple electrostatic interactions.

    PubMed

    Taylor, M A; Baker, K C; Connerton, I F; Cummings, N J; Harris, G W; Henderson, I M; Jones, S T; Pickersgill, R W; Sumner, I G; Warwicker, J

    1994-10-01

    The role of electrostatic interactions between the ionizable Asp158 and the active site thiolate-imidazolium ion pair of some cysteine proteinases has been the subject of controversy for some time. This study reports the expression of wild type procaricain and Asp158Glu, Asp158Asn and Asp158Ala mutants from Escherichia coli. Purification of autocatalytically matured enzymes yielded sufficient fully active material for pH (kcat/Km) profiles to be obtained. Use of both uncharged and charged substrates allowed the effects of different reactive enzyme species to be separated from the complications of electrostatic effects between enzyme and substrate. At least three ionizations are detectable in the acid limb of wild type caricain and the Glu and Asn mutants. Only two pKa values, however, are detectable in the acid limb using the Ala mutant. Comparison of pH activity profiles shows that whilst an ionizable residue at position 158 is not essential for the formation of the thiolate-imidazolium ion pair, it does form a substantial part of the electrostatic field responsible for increased catalytic competence. Changing the position of this ionizable group in any way reduces activity. Complete removal of the charged group reduces catalytic competence even further. This work indicates that hydronations distant to the active site are contributing to the electrostatic effects leading to multiple active ionization states of the enzyme. PMID:7855143

  14. Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV Reactivation.

    PubMed

    Iannetta, Marco; Zingaropoli, Maria Antonella; Bellizzi, Anna; Morreale, Manuela; Pontecorvo, Simona; D'Abramo, Alessandra; Oliva, Alessandra; Anzivino, Elena; Lo Menzo, Sara; D'Agostino, Claudia; Mastroianni, Claudio Maria; Millefiorini, Enrico; Pietropaolo, Valeria; Francia, Ada; Vullo, Vincenzo; Ciardi, Maria Rosa

    2016-01-01

    The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects. PMID:27486658

  15. How multiple social networks affect user awareness: The information diffusion process in multiplex networks

    NASA Astrophysics Data System (ADS)

    Li, Weihua; Tang, Shaoting; Fang, Wenyi; Guo, Quantong; Zhang, Xiao; Zheng, Zhiming

    2015-10-01

    The information diffusion process in single complex networks has been extensively studied, especially for modeling the spreading activities in online social networks. However, individuals usually use multiple social networks at the same time, and can share the information they have learned from one social network to another. This phenomenon gives rise to a new diffusion process on multiplex networks with more than one network layer. In this paper we account for this multiplex network spreading by proposing a model of information diffusion in two-layer multiplex networks. We develop a theoretical framework using bond percolation and cascading failure to describe the intralayer and interlayer diffusion. This allows us to obtain analytical solutions for the fraction of informed individuals as a function of transmissibility T and the interlayer transmission rate θ . Simulation results show that interaction between layers can greatly enhance the information diffusion process. And explosive diffusion can occur even if the transmissibility of the focal layer is under the critical threshold, due to interlayer transmission.

  16. An olfactory-limbic model of multiple chemical sensitivity syndrome: Possible relationships to kindling and affective spectrum disorders

    SciTech Connect

    Bell, I.R.; Miller, C.S.; Schwartz, G.E. )

    1992-08-01

    This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. 170 refs.

  17. Altered precipitation regime affects the function and composition of soil microbial communities on multiple time scales.

    PubMed

    Zeglin, L H; Bottomley, P J; Jumpponen, A; Rice, C W; Arango, M; Lindsley, A; McGowan, A; Mfombep, P; Myrold, D D

    2013-10-01

    Climate change models predict that future precipitation patterns will entail lower-frequency but larger rainfall events, increasing the duration of dry soil conditions. Resulting shifts in microbial C cycling activity could affect soil C storage. Further, microbial response to rainfall events may be constrained by the physiological or nutrient limitation stress of extended drought periods; thus seasonal or multiannual precipitation regimes may influence microbial activity following soil wet-up. We quantified rainfall-driven dynamics of microbial processes that affect soil C loss and retention, and microbial community composition, in soils from a long-term (14-year) field experiment contrasting "Ambient" and "Altered" (extended intervals between rainfalls) precipitation regimes. We collected soil before, the day following, and five days following 2.5-cm rainfall events during both moist and dry periods (June and September 2011; soil water potential = -0.01 and -0.83 MPa, respectively), and measured microbial respiration, microbial biomass, organic matter decomposition potential (extracellular enzyme activities), and microbial community composition (phospholipid fatty acids). The equivalent rainfall events caused equivalent microbial respiration responses in both treatments. In contrast, microbial biomass was higher and increased after rainfall in the Altered treatment soils only, thus microbial C use efficiency (CUE) was higher in Altered than Ambient treatments (0.70 +/- 0.03 > 0.46 +/- 0.10). CUE was also higher in dry (September) soils. C-acquiring enzyme activities (beta-glucosidase, cellobiohydrolase, and phenol oxidase) increased after rainfall in moist (June), but not dry (September) soils. Both microbial biomass C:N ratios and fungal:bacterial ratios were higher at lower soil water contents, suggesting a functional and/or population-level shift in the microbiota at low soil water contents, and microbial community composition also differed following wet

  18. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats

    SciTech Connect

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-12-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 {mu}g/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor {beta} was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.

  19. Developmental Methoxychlor Exposure Affects Multiple Reproductive Parameters and Ovarian: Folliculogenesis and Gene Expression in Adult Rats

    PubMed Central

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-01-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 μg/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post-coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor β was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis. PMID:18848953

  20. Disability Progression in Multiple Sclerosis Is Affected by the Emergence of Comorbid Arterial Hypertension

    PubMed Central

    Dagan, Amir; Gringouz, Irina; Kliers, Iris

    2016-01-01

    Background and Purpose We assessed the prevalence and potential association of hypertension with multiple sclerosis (MS)-related disability progression. Methods This was a retrospective study of 2,813 patients who were followed for 20 years. We modeled the associations of several risk factors with the pattern of disability progression. The primary end point was the rate of disability progression. Results In total, 2,396 patients were available for analysis, of which 1,074 (44.8%) scored 4 (EDSS4) on the Expanded Disability Status Scale (EDSS), 717 (29.9%) scored 6 (EDSS6), and 261 (10.9%) scored 8 (EDSS8). The mean times to reach scores of 4, 6, and 8 were 123.5, 163.1, and 218.9 months, respectively. Hypertension was present in 207 (8.6%) patients during follow-up. Hypertension was associated with a higher probability of reaching each EDSS score compared to non-hypertensive patients: 62% vs. 43% for EDSS4 (p<0.01), 51% vs. 28% for EDSS6 (p<0.01), and 17% vs. 10% for EDSS8 (p<0.01). Nevertheless, hypertensive MS patients experienced longer intervals to reach each EDSS score: longer by 51.6, 38.9, and 62.7 months to EDSS4, EDSS6, and EDSS8, respectively (p<0.01) when compared to non-hypertensive MS patients reaching the same EDSS scores. Conclusions Disability progression is more prevalent amongst hypertensive MS patients. However, they experience longer time intervals between the stages of disability progression. PMID:27273922

  1. Multiple factors affect a population of Agassiz's desert tortoise (Gopherus agassizii) in the Northwestern Mojave Desert

    USGS Publications Warehouse

    Berry, Kristin H.; Yee, Julie L.; Coble, Ashley A.; Perry, William M.; Shields, Timothy A.

    2013-01-01

    Numerous factors have contributed to declines in populations of the federally threatened Agassiz's Desert Tortoise (Gopherus agassizii) and continue to limit recovery. In 2010, we surveyed a low-density population on a military test facility in the northwestern Mojave Desert of California, USA, to evaluate population status and identify potential factors contributing to distribution and low densities. Estimated densities of live tortoises ranged spatially from 1.2/km2 to 15.1/km2. Although only one death of a breeding-age tortoise was recorded for the 4-yr period prior to the survey, remains of 16 juvenile and immature tortoises were found, and most showed signs of predation by Common Ravens (Corvus corax) and mammals. Predation may have limited recruitment of young tortoises into the adult size classes. To evaluate the relative importance of different types of impacts to tortoises, we developed predictive models for spatially explicit densities of tortoise sign and live tortoises using topography (i.e., slope), predators (Common Raven, signs of mammalian predators), and anthropogenic impacts (distances from paved road and denuded areas, density of ordnance fragments) as covariates. Models suggest that densities of tortoise sign increased with slope and signs of mammalian predators and decreased with Common Ravens, while also varying based on interaction effects involving these predictors as well as distances from paved roads, denuded areas, and ordnance. Similarly, densities of live tortoises varied by interaction effects among distances to denuded areas and paved roads, density of ordnance fragments, and slope. Thus multiple factors predict the densities and distribution of this population.

  2. Plasticity and epistasis strongly affect bacterial fitness after losing multiple metabolic genes.

    PubMed

    D'Souza, Glen; Waschina, Silvio; Kaleta, Christoph; Kost, Christian

    2015-05-01

    Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epistasis on the fitness of Escherichia coli genotypes from whose genome biosynthetic genes for one, two, or three different amino acids have been deleted. Competitive fitness experiments between auxotrophic mutants and prototrophic wild-type cells in one of two carbon environments revealed that plasticity and epistasis strongly affected the mutants' fitness individually and interactively. Positive and negative epistatic interactions were prevalent, yet on average cancelled each other out. Moreover, epistasis correlated negatively with the expected effects of combined auxotrophy-causing mutations, thus producing a pattern of diminishing returns. Moreover, computationally analyzing 1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co-occurred significantly more often than expected by chance, suggesting epistatic interactions and/or environmental factors favored these combinations. Our results demonstrate that both the genetic background and environmental conditions determine the adaptive value of a loss-of-biochemical-function mutation and that fitness gains decelerate, as more biochemical functions are lost. PMID:25765095

  3. Methoxychlor affects multiple hormone signaling pathways in the largemouth bass (Micropterus salmoides) liver

    PubMed Central

    Martyniuk, Christopher J.; Spade, Daniel J.; Blum, Jason L.; Kroll, Kevin J.; Denslow, Nancy D.

    2011-01-01

    Methoxychlor (MXC) is an organochlorine pesticide that has been shown to have estrogenic activity by activating estrogen receptors and inducing vitellogenin production in male fish. Previous studies report that exposure to MXC induces changes in mRNA abundance of reproductive genes in the liver and testes of largemouth bass (Micropterus salmoides). The objective of the present study was to better characterize the mode of action of MXC by measuring the global transcriptomic response in the male largemouth liver using an oligonucleotide microarray. Microarray analysis identified highly significant changes in the expression of 37 transcripts (p<0.001) (20 induced and 17 decreased) in the liver after MXC injection and a total of 900 expression changes (p<0.05) in transcripts with high homology to known genes. Largemouth bass estrogen receptor alpha (esr1) and androgen receptor (ar) were among the transcripts that were increased in the liver after MXC treatment. Functional enrichment analysis identified the molecular functions of steroid binding and androgen receptor activity as well as steroid hormone receptor activity as being significantly over-represented gene ontology terms. Pathway analysis identified c-fos signaling as being putatively affected through both estrogen and androgen signaling. This study provides evidence that MXC elicits transcriptional effects through the estrogen receptor as well as androgen receptor-mediated pathways in the liver. PMID:21276474

  4. Multiple dietary supplements do not affect metabolic and cardio-vascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2014-02-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  5. Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis.

    PubMed

    Slayden, R A; Lee, R E; Barry, C E

    2000-11-01

    Genetic and biochemical evidence has implicated two different target enzymes for isoniazid (INH) within the unique type II fatty acid synthase (FAS) system involved in the production of mycolic acids. These two components are an enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA. We compared the consequences of INH treatment of Mycobacterium tuberculosis (MTB) with two inhibitors having well-defined targets: triclosan (TRC), which inhibits InhA; and thiolactomycin (TLM), which inhibits KasA. INH and TLM, but not TRC, upregulate the expression of an operon containing five FAS II components, including kasA and acpM. Although all three compounds inhibit mycolic acid synthesis, treatment with INH and TLM, but not with TRC, results in the accumulation of ACP-bound lipid precursors to mycolic acids that were 26 carbons long and fully saturated. TLM-resistant mutants of MTB were more cross-resistant to INH than TRC-resistant mutants. Overexpression of KasA conferred more resistance to TLM and INH than to TRC. Overexpression of InhA conferred more resistance to TRC than to INH and TLM. Co-overexpression of both InhA and KasA resulted in strongly enhanced levels of INH resistance, in addition to cross-resistance to both TLM and TRC. These results suggest that these components of the FAS II complex are not independently regulated and that alterations in the expression level of InhA affect expression levels of KasA. Nonetheless, INH appeared to resemble TLM more closely in overall mode of action, and KasA levels appeared to be tightly correlated with INH sensitivity. PMID:11069675

  6. Glycerol Affects Root Development through Regulation of Multiple Pathways in Arabidopsis

    PubMed Central

    Hu, Jun; Zhang, Yonghong; Wang, Jinfang; Zhou, Yongming

    2014-01-01

    treatment altered endogenous levels of G3P, phosphate and ROS, affected auxin distribution and cell division in the root meristem, and eventually resulted in modifications of root development. PMID:24465999

  7. Glycerol affects root development through regulation of multiple pathways in Arabidopsis.

    PubMed

    Hu, Jun; Zhang, Yonghong; Wang, Jinfang; Zhou, Yongming

    2014-01-01

    treatment altered endogenous levels of G3P, phosphate and ROS, affected auxin distribution and cell division in the root meristem, and eventually resulted in modifications of root development. PMID:24465999

  8. Pep3p/Pep5p complex: a putative docking factor at multiple steps of vesicular transport to the vacuole of Saccharomyces cerevisiae.

    PubMed Central

    Srivastava, A; Woolford, C A; Jones, E W

    2000-01-01

    Pep3p and Pep5p are known to be necessary for trafficking of hydrolase precursors to the vacuole and for vacuolar biogenesis. These proteins are present in a hetero-oligomeric complex that mediates transport at the vacuolar membrane. PEP5 interacts genetically with VPS8, implicating Pep5p in the earlier Golgi to endosome step and/or in recycling from the endosome to the Golgi. To understand further the cellular roles of Pep3p and Pep5p, we isolated and characterized a set of pep3 conditional mutants. Characterization of mutants revealed that pep3(ts) mutants are defective in the endosomal and nonendosomal Golgi to vacuole transport pathways, in the cytoplasm to vacuole targeting pathway, in recycling from the endosome back to the late Golgi, and in endocytosis. PEP3 interacts genetically with two members of the endosomal SNARE complex, PEP12 (t-SNARE) and PEP7 (homologue of mammalian EEA1); Pep3p and Pep5p associate physically with Pep7p as revealed by two-hybrid analysis. Our results suggest that a core Pep3p/Pep5p complex promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole. We propose that this complex may be responsible for tethering transport vesicles on target membranes. PMID:10978279

  9. Security: Step by Step

    ERIC Educational Resources Information Center

    Svetcov, Eric

    2005-01-01

    This article provides a list of the essential steps to keeping a school's or district's network safe and sound. It describes how to establish a security architecture and approach that will continually evolve as the threat environment changes over time. The article discusses the methodology for implementing this approach and then discusses the…

  10. The ASYMMETRIC LEAVES Complex Employs Multiple Modes of Regulation to Affect Adaxial-Abaxial Patterning and Leaf Complexity[OPEN

    PubMed Central

    Husbands, Aman Y.; Benkovics, Anna H.; Nogueira, Fabio T.S.; Lodha, Mukesh; Timmermans, Marja C.P.

    2015-01-01

    Flattened leaf architecture is not a default state but depends on positional information to precisely coordinate patterns of cell division in the growing primordium. This information is provided, in part, by the boundary between the adaxial (top) and abaxial (bottom) domains of the leaf, which are specified via an intricate gene regulatory network whose precise circuitry remains poorly defined. Here, we examined the contribution of the ASYMMETRIC LEAVES (AS) pathway to adaxial-abaxial patterning in Arabidopsis thaliana and demonstrate that AS1-AS2 affects this process via multiple, distinct regulatory mechanisms. AS1-AS2 uses Polycomb-dependent and -independent mechanisms to directly repress the abaxial determinants MIR166A, YABBY5, and AUXIN RESPONSE FACTOR3 (ARF3), as well as a nonrepressive mechanism in the regulation of the adaxial determinant TAS3A. These regulatory interactions, together with data from prior studies, lead to a model in which the sequential polarization of determinants, including AS1-AS2, explains the establishment and maintenance of adaxial-abaxial leaf polarity. Moreover, our analyses show that the shared repression of ARF3 by the AS and trans-acting small interfering RNA (ta-siRNA) pathways intersects with additional AS1-AS2 targets to affect multiple nodes in leaf development, impacting polarity as well as leaf complexity. These data illustrate the surprisingly multifaceted contribution of AS1-AS2 to leaf development showing that, in conjunction with the ta-siRNA pathway, AS1-AS2 keeps the Arabidopsis leaf both flat and simple. PMID:26589551

  11. How the multiple antioxidant properties of ascorbic acid affect lipid oxidation in oil-in-water emulsions.

    PubMed

    Uluata, Sibel; McClements, D Julian; Decker, Eric A

    2015-02-18

    Lipid oxidation is a serious problem for oil-containing food products because it negatively affects shelf life and nutritional composition. An antioxidant strategy commonly employed to prevent or delay oxidation in foods is to remove oxygen from the closed food-packaging system. An alternative technique is use of an edible oxygen scavenger to remove oxygen within the food. Ascorbic acid (AA) is a particularly promising antioxidant because of its natural label and multiple antioxidative functions. In this study, AA was tested as an oxygen scavenger in buffer and an oil-in-water (O/W) emulsion. The effects of transition metals on the ability of AA to scavenge oxygen were determined. Headspace oxygen decrease less than 1% in the medium-chain triacylglycerol (MCT) O/W emulsion system (pH 3 and 7). AA was able to almost completely remove dissolved oxygen (DO) in a buffered solution. Transition metals (Fe(2+) and Cu(+)) significantly accelerated the degradation of AA; however, iron and copper only increased DO depletion rates, by 10.6-16.4% from day 1 to 7, compared to the control. AA (2.5-20 mM) decreased DO in a 1% O/W emulsion system 32.0-64.0% and delayed the formation of headspace hexanal in the emulsion from 7 to over 20 days. This research shows that, when AA is used in an O/W emulsion system, oxidation of the emulsion system can be delay by multiple mechanisms. PMID:25650525

  12. Homolog-focused profiling of ginsenosides based on the integration of step-wise formate anion-to-deprotonated ion transition screening and scheduled multiple reaction monitoring.

    PubMed

    Song, Yuelin; Zhang, Na; Shi, Shepo; Li, Jun; Zhao, Yunfang; Zhang, Qian; Jiang, Yong; Tu, Pengfei

    2015-08-01

    Homolog-focused profiling is a favored option to bridge targeted metabolomics toward non-targeted metabolomics. In current study, an attempt was made for the large-scale ginsenoside-specific analysis in ginseng (G) and American ginseng (AG). When formic acid (0.1%, v/v) was introduced as the mobile phase additive, formate anion-to-deprotonated ion transitions ([M+HCOO](-)>[M-H](-)) with an optimal collision energy (-32eV) could result in satisfactory responses for ginsenosides. Therefore, a step-wise multiple reaction monitoring (MRM)-based method employing [M+HCOO](-)>[M-H](-) ion pairs was constructed to screen ginsenosides among 501-1250u (for Q1) with a step-size of 2u, and MRM also served as a survey experiment to trigger enhanced product ion scans for MS(2) spectrum acquisition on a hybrid triple quadrupole-linear ion trap mass spectrometer; then, the identification of those observed ginsenosides was achieved on the basis of the well-defined mass cracking patterns for ginsenosides; afterwards, scheduled MRM was introduced for large-scale relatively quantitative analysis of all detected ginsenosides. Finally, comparative metabolomics were performed to differentiate G, AG, and their processed products. Method validation was carried out using thirteen authentic compounds. A total of 221 ginsenosides, among which 185 ones were annotated, were observed and relatively quantitated. All crude materials were obviously classified into groups I-III. Above all, the MRM-based homolog-focused profiling of ginsenosides could be used as a reliable tool to gain an in-depth view for ginsenoside-enriched herbal products. PMID:26105782

  13. Successful multiple-step management of intravenous leiomyomatosis diagnosed after episode of acute abdominal pain: Case report and review of literature

    PubMed Central

    Efthimiadis, Christoforos; Petousis, Stamatios; Grigoriou, Marios; Ioannidis, Aristeidis; Tzouveleki, Ioanna; Margioula-Siarkou, Chrysoula; Kalogiannidis, Ioannis

    2015-01-01

    Introduction We present the case of a 37-year old woman diagnosed with intravenous leiomyomatosis (IVL) that was managed uneventfully with multiple-step management. Presentation of case A 37-year-old woman was admitted because of acute abdominal pain. Emergency Computed Tomography demonstrated a big pelvic mass 5 × 15 cm of heterogenous composition intaking the contrast agent. Total hysterectomy with salpingoophorectomy was proposed to patient, however, patient expressed her will for fertility preservation and gave consent only for the resection of a single ovary. Laparotomy revealed the presence of myoma, multiple lesions of potential adenomyosis and cordon-shaped formations arising from uterus and extending mainly to left ovary. Final histological diagnosis was intravenous leiomyomatosis (IVL). MRI angiography revealed the presence of residual lesions in inferior vena cava. Laparoscopic resection was performed one month after laparotomy and left ovary was resected without complications. Venovenous bypass was finally performed three months later from initial surgery. The process was significantly labored, resulted in the successful resection of intravenous lesions but was complicated intraoperatively by right kidney rupture. After a follow-up of 33 months, case remains uncomplicated without signs or symptoms of potential recurrence. Discussion Intravenous leiomyomatosis represents a rare clinical entity histologically bening but clinically aggressive. No consensus exists regarding the optimal management, especially in cases with initial will for fertility preservation. Conclusion IVL represents a rare clinical entity often presenting difficulties in diagnosis and optimal treatment. Large case-series studies should be encouraged to assess the optimal management. PMID:26282558

  14. Next Step for STEP

    SciTech Connect

    Wood, Claire; Bremner, Brenda

    2013-08-09

    The Siletz Tribal Energy Program (STEP), housed in the Tribe’s Planning Department, will hire a data entry coordinator to collect, enter, analyze and store all the current and future energy efficiency and renewable energy data pertaining to administrative structures the tribe owns and operates and for homes in which tribal members live. The proposed data entry coordinator will conduct an energy options analysis in collaboration with the rest of the Siletz Tribal Energy Program and Planning Department staff. An energy options analysis will result in a thorough understanding of tribal energy resources and consumption, if energy efficiency and conservation measures being implemented are having the desired effect, analysis of tribal energy loads (current and future energy consumption), and evaluation of local and commercial energy supply options. A literature search will also be conducted. In order to educate additional tribal members about renewable energy, we will send four tribal members to be trained to install and maintain solar panels, solar hot water heaters, wind turbines and/or micro-hydro.

  15. The Aurora-A inhibitor MLN8237 affects multiple mitotic processes and induces dose-dependent mitotic abnormalities and aneuploidy

    PubMed Central

    Asteriti, Italia Anna; Cesare, Erica Di; Mattia, Fabiola De; Hilsenstein, Volker; Neumann, Beate; Cundari, Enrico; Lavia, Patrizia; Guarguaglini, Giulia

    2014-01-01

    Inhibition of Aurora kinase activity by small molecules is being actively investigated as a potential anti-cancer strategy. A successful therapeutic use of Aurora inhibitors relies on a comprehensive understanding of the effects of inactivating Aurora kinases on cell division, a challenging aim given the pleiotropic roles of those kinases during mitosis. Here we have used the Aurora-A inhibitor MLN8237, currently under phase-I/III clinical trials, in dose-response assays in U2OS human cancer cells synchronously proceeding towards mitosis. By following the behaviour and fate of single Aurora-inhibited cells in mitosis by live microscopy, we show that MLN8237 treatment affects multiple processes that are differentially sensitive to the loss of Aurora-A function. A role of Aurora-A in controlling the orientation of cell division emerges. MLN8237 treatment, even in high doses, fails to induce efficient elimination of dividing cells, or of their progeny, while inducing significant aneuploidy in daughter cells. The results of single-cell analyses show a complex cellular response to MLN8237 and evidence that its effects are strongly dose-dependent: these issues deserve consideration in the light of the design of strategies to kill cancer cells via inhibition of Aurora kinases. PMID:25153724

  16. The Aurora-A inhibitor MLN8237 affects multiple mitotic processes and induces dose-dependent mitotic abnormalities and aneuploidy.

    PubMed

    Asteriti, Italia Anna; Di Cesare, Erica; De Mattia, Fabiola; Hilsenstein, Volker; Neumann, Beate; Cundari, Enrico; Lavia, Patrizia; Guarguaglini, Giulia

    2014-08-15

    Inhibition of Aurora kinase activity by small molecules is being actively investigated as a potential anti-cancer strategy. A successful therapeutic use of Aurora inhibitors relies on a comprehensive understanding of the effects of inactivating Aurora kinases on cell division, a challenging aim given the pleiotropic roles of those kinases during mitosis. Here we have used the Aurora-A inhibitor MLN8237, currently under phase-I/III clinical trials, in dose-response assays in U2OS human cancer cells synchronously proceeding towards mitosis. By following the behaviour and fate of single Aurora-inhibited cells in mitosis by live microscopy, we show that MLN8237 treatment affects multiple processes that are differentially sensitive to the loss of Aurora-A function. A role of Aurora-A in controlling the orientation of cell division emerges. MLN8237 treatment, even in high doses, fails to induce efficient elimination of dividing cells, or of their progeny, while inducing significant aneuploidy in daughter cells. The results of single-cell analyses show a complex cellular response to MLN8237 and evidence that its effects are strongly dose-dependent: these issues deserve consideration in the light of the design of strategies to kill cancer cells via inhibition of Aurora kinases. PMID:25153724

  17. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  18. To Fish or Not to Fish: Factors at Multiple Scales Affecting Artisanal Fishers' Readiness to Exit a Declining Fishery

    PubMed Central

    Daw, Tim M.; Cinner, Joshua E.; McClanahan, Timothy R.; Brown, Katrina; Stead, Selina M.; Graham, Nicholas A. J.; Maina, Joseph

    2012-01-01

    Globally, fisheries are challenged by the combined impacts of overfishing, degradation of ecosystems and impacts of climate change, while fisheries livelihoods are further pressured by conservation policy imperatives. Fishers' adaptive responses to these pressures, such as exiting from a fishery to pursue alternative livelihoods, determine their own vulnerability, as well as the potential for reducing fishing effort and sustaining fisheries. The willingness and ability to make particular adaptations in response to change, such as exiting from a declining fishery, is influenced by economic, cultural and institutional factors operating at scales from individual fishers to national economies. Previous studies of exit from fisheries at single or few sites, offer limited insight into the relative importance of individual and larger-scale social and economic factors. We asked 599 fishers how they would respond to hypothetical scenarios of catch declines in 28 sites in five western Indian Ocean countries. We investigated how socioeconomic variables at the individual-, household- and site-scale affected whether they would exit fisheries. Site-level factors had the greatest influence on readiness to exit, but these relationships were contrary to common predictions. Specifically, higher levels of infrastructure development and economic vitality - expected to promote exit from fisheries - were associated with less readiness to exit. This may be due to site level histories of exit from fisheries, greater specialisation of fishing households, or higher rewards from fishing in more economically developed sites due to technology, market access, catch value and government subsidies. At the individual and household scale, fishers from households with more livelihood activities, and fishers with lower catch value were more willing to exit. These results demonstrate empirically how adaptive responses to change are influenced by factors at multiple scales, and highlight the importance

  19. To fish or not to fish: factors at multiple scales affecting artisanal fishers' readiness to exit a declining fishery.

    PubMed

    Daw, Tim M; Cinner, Joshua E; McClanahan, Timothy R; Brown, Katrina; Stead, Selina M; Graham, Nicholas A J; Maina, Joseph

    2012-01-01

    Globally, fisheries are challenged by the combined impacts of overfishing, degradation of ecosystems and impacts of climate change, while fisheries livelihoods are further pressured by conservation policy imperatives. Fishers' adaptive responses to these pressures, such as exiting from a fishery to pursue alternative livelihoods, determine their own vulnerability, as well as the potential for reducing fishing effort and sustaining fisheries. The willingness and ability to make particular adaptations in response to change, such as exiting from a declining fishery, is influenced by economic, cultural and institutional factors operating at scales from individual fishers to national economies. Previous studies of exit from fisheries at single or few sites, offer limited insight into the relative importance of individual and larger-scale social and economic factors. We asked 599 fishers how they would respond to hypothetical scenarios of catch declines in 28 sites in five western Indian Ocean countries. We investigated how socioeconomic variables at the individual-, household- and site-scale affected whether they would exit fisheries. Site-level factors had the greatest influence on readiness to exit, but these relationships were contrary to common predictions. Specifically, higher levels of infrastructure development and economic vitality - expected to promote exit from fisheries - were associated with less readiness to exit. This may be due to site level histories of exit from fisheries, greater specialisation of fishing households, or higher rewards from fishing in more economically developed sites due to technology, market access, catch value and government subsidies. At the individual and household scale, fishers from households with more livelihood activities, and fishers with lower catch value were more willing to exit. These results demonstrate empirically how adaptive responses to change are influenced by factors at multiple scales, and highlight the importance

  20. Multiple- and single-molecule analysis of the actomyosin motor by nanometer-piconewton manipulation with a microneedle: unitary steps and forces.

    PubMed Central

    Ishijima, A; Kojima, H; Higuchi, H; Harada, Y; Funatsu, T; Yanagida, T

    1996-01-01

    We have developed a new technique for measurements of piconewton forces and nanometer displacements in the millisecond time range caused by actin-myosin interaction in vitro by manipulating single actin filaments with a glass microneedle. Here, we describe in full the details of this method. Using this method, the elementary events in energy transduction by the actomyosin motor, driven by ATP hydrolysis, were directly recorded from multiple and single molecules. We found that not only the velocity but also the force greatly depended on the orientations of myosin relative to the actin filament axis. Therefore, to avoid the effects of random orientation of myosin and association of myosin with an artificial substrate in the surface motility assay, we measured forces and displacements by myosin molecules correctly oriented in single synthetic myosin rod cofilaments. At a high myosin-to-rod ratio, large force fluctuations were observed when the actin filament interacted in the correct orientation with a cofilament. The noise analysis of the force fluctuations caused by a small number of heads showed that the myosin head generated a force of 5.9 +/- 0.8 pN at peak and 2.1 +/- 0.4 pN on average over the whole ATPase cycle. The rate constants for transitions into (k+) and out of (k-) the force generation state and the duty ratio were 12 +/- 2 s-1, and 22 +/- 4 s-1, and 0.36 +/- 0.07, respectively. The stiffness was 0.14 pN nm-1 head-1 for slow length change (100 Hz), which would be approximately 0.28 pN nm-1 head-1 for rapid length change or in rigor. At a very low myosin-to-rod ratio, distinct actomyosin attachment, force generation (the power stroke), and detachment events were directly detected. At high load, one power stroke generated a force spike with a peak value of 5-6 pN and a duration of 50 ms (k(-)-1), which were compatible with those of individual myosin heads deduced from the force fluctuations. As the load was reduced, the force of the power stroke decreased

  1. Technology-Aided Leisure and Communication Opportunities for Two Post-Coma Persons Emerged from a Minimally Conscious State and Affected by Multiple Disabilities

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Buonocunto, Francesca; Sacco, Valentina; Navarro, Jorge; Lanzilotti, Crocifissa; De Tommaso, Marina; Megna, Marisa; Oliva, Doretta

    2013-01-01

    This study assessed technology-aided programs for helping two post-coma persons, who had emerged from a minimally conscious state and were affected by multiple disabilities, to (a) engage with leisure stimuli and request caregiver's procedures, (b) send out and listen to text messages for communication with distant partners, and (c) combine…

  2. Gait variability in healthy old adults is more affected by a visual perturbation than by a cognitive or narrow step placement demand.

    PubMed

    Francis, Carrie A; Franz, Jason R; O'Connor, Shawn M; Thelen, Darryl G

    2015-09-01

    Gait variability measures have been linked to fall risk in older adults. However, challenging walking tasks may be required to elucidate increases in variability that arise from subtle age-related changes in cognitive processing and sensorimotor function. Hence, the study objective was to investigate the effects of visual perturbations, increased cognitive load, and narrowed step width on gait variability in healthy old and young adults. Eleven old (OA, 71.2±4.2 years) and twelve young (YA, 23.6±3.9 years) adults walked on a treadmill while watching a speed-matched virtual hallway. Subjects walked: (1) normally, (2) with mediolateral visual perturbations, (3) while performing a cognitive task (serial seven subtractions), and (4) with narrowed step width. We computed the mean and variability of step width (SW and SWV, respectively) and length (SL, SLV) over one 3-min trial per condition. Walking normally, old and young adults exhibited similar SWV and SLV. Visual perturbations significantly increased gait variability in old adults (by more than 100% for both SWV and SLV), but not young adults. The cognitive task and walking with narrowed step width did not show any effect on SWV or SLV in either group. The dramatic increase in step width variability when old adults were subjected to mediolateral visual perturbations was likely due to increased reliance on visual feedback for assessing whole-body position. Further work is needed to ascertain whether these findings may reflect sub-clinical balance deficits that could contribute to the increased fall risk seen with advancing age. PMID:26233581

  3. Separation of Competency and Affect Components of Multiple Dimensions of Academic Self-Concept: A Developmental Perspective.

    ERIC Educational Resources Information Center

    Marsh, Herbert W.; Craven, Rhonda; Debus, Raymond

    1999-01-01

    Examined how separation of competency and affect components of self-concept domains varied in 7- to 13-year-olds. Found that Self-Description Questionnaire factor loadings were invariant over age comparisons. Correlations among reading, math, and school self-concepts decreased with age. Correlations between competency and affect within domains…

  4. Predicting probability of occurrence and factors affecting distribution and abundance of three Ozark endemic crayfish species at multiple spatial scales

    USGS Publications Warehouse

    Nolen, Matthew S.; Magoulick, Daniel D.; DiStefano, Robert J.; Imhoff, Emily M.; Wagner, Brian K.

    2014-01-01

    We found that a range of environmental variables were important in predicting crayfish distribution and abundance at multiple spatial scales and their importance was species-, response variable- and scale dependent. We would encourage others to examine the influence of spatial scale on species distribution and abundance patterns.

  5. Using Multiple Calibration Indices in Order to Capture the Complex Picture of What Affects Students' Accuracy of Feeling of Confidence

    ERIC Educational Resources Information Center

    Boekaerts, Monique; Rozendaal, Jeroen S.

    2010-01-01

    The present study used multiple calibration indices to capture the complex picture of fifth graders' calibration of feeling of confidence in mathematics. Specifically, the effects of gender, type of mathematical problem, instruction method, and time of measurement (before and after problem solving) on calibration skills were investigated. Fourteen…

  6. Assessment of factors which affect multiple uses of water sources at household level in rural Zimbabwe - A case study of Marondera, Murehwa and Uzumba Maramba Pfungwe districts

    NASA Astrophysics Data System (ADS)

    Katsi, Luckson; Siwadi, Japson; Guzha, Edward; Makoni, Fungai S.; Smits, Stef

    Water with all its multiple uses plays a pivotal role in the sustenance of rural livelihoods, especially the poor. As such, the provision of water which go beyond domestic to include water for small-scale productive uses should be encouraged to enhance peoples’ livelihood options by making significant contribution to household income, food security, improved nutrition and health. All these multiple benefits, if combined can assist in the fight against hunger and poverty. This study was conducted in Mashonaland East province, covering Marondera, Murehwa and Uzumba Maramba Pfungwe districts in Zimbabwe for the period December 2005-May 2006 to assess factors which affect multiple uses of water sources at household level. Participatory Rural Appraisal tools such as discussions, observations and interviews were used for data collection. The survey found that people indeed require water for productive purposes apart from domestic uses, which are often given top priority. The study found out that multiple uses of water sources at household level can be affected by segmentation of water services into domestic and productive water supply schemes, technology and system design, water quality and quantity and distance to water sources among other factors. The study recommends that water service providers to be able to provide appropriate, efficient and sustainable services, they should understand and appreciate that people’s water needs are integrated and are part and parcel of their multifaceted livelihood strategies.

  7. PHOEBE - step by step manual

    NASA Astrophysics Data System (ADS)

    Zasche, P.

    2016-03-01

    An easy step-by-step manual of PHOEBE is presented. It should serve as a starting point for the first time users of PHOEBE analyzing the eclipsing binary light curve. It is demonstrated on one particular detached system also with the downloadable data and the whole procedure is described easily till the final trustworthy fit is being reached.

  8. Step Pultrusion

    NASA Astrophysics Data System (ADS)

    Langella, A.; Carbone, R.; Durante, M.

    2012-12-01

    The pultrusion process is an efficient technology for the production of composite material profiles. Thanks to this positive feature, several studies have been carried out, either to expand the range of products made using the pultrusion technology, or improve its already high production rate. This study presents a process derived from the traditional pultrusion technology named "Step Pultrusion Process Technology" (SPPT). Using the step pultrusion process, the final section of the composite profiles is obtainable by means of a progressive cross section increasing through several resin cure stations. This progressive increasing of the composite cross section means that a higher degree of cure level can be attained at the die exit point of the last die. Mechanical test results of the manufactured pultruded samples have been used to compare both the traditional and the step pultrusion processes. Finally, there is a discussion on ways to improve the new step pultrusion process even further.

  9. One-step multiple component isolation from the oil of Crinitaria tatarica (Less) Sojak by preparative capillary gas chromatography with characterization by spectroscopic and spectrometric techniques

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present work multiple component isolation from the oil of Crinitaria tatarica (Less.) Sojak. by Preparative Capillary Gas Chromatography (PCGC) with characterization by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have been carried out. Gas chromatography (GC-FID) ...

  10. Does migratory distance affect fuelling in a medium-distance passerine migrant?: results from direct and step-wise simulated magnetic displacements

    PubMed Central

    Ilieva, Mihaela; Bianco, Giuseppe; Åkesson, Susanne

    2016-01-01

    ABSTRACT In birds, fat accumulation before and during migration has been shown to be endogenously controlled and tuned by, among other factors, the Earth's magnetic field. However, our knowledge about the influence of the geomagnetic field on the fuelling in migrating birds is still limited to just a few nocturnally migrating passerine species. In order to study if variations of the magnetic field can also influence the fuelling of both day- and night-migrating passerines, we caught first-year dunnocks (Prunella modularis) and subjected them to three magnetic field conditions simulated by a system of magnetic coils: (1) local geomagnetic field of southern Sweden, (2) magnetic field corresponding to the centre of the expected wintering area, and (3) magnetic field met at the northern limit of the species' breeding distribution. We did not find a difference in mass increase between the birds kept in a local magnetic field and a field resembling their wintering area, irrespectively of the mode of magnetic displacement, i.e. direct or step-wise. However, the dunnocks magnetically displaced north showed a lower rate of fuelling in comparison to the control group, probably due to elevated activity. Compared with previous studies, our results suggest that the fuelling response to magnetic displacements during the migration period is specific to the eco-physiological situation. Future studies need to address if there is an effect of magnetic field manipulation on the level of migratory activity in dunnocks and how widespread the influence of local geomagnetic field parameters is on fuelling decisions in different bird species, which have different migratory strategies, distances and migration history. PMID:26883627

  11. Does migratory distance affect fuelling in a medium-distance passerine migrant?: results from direct and step-wise simulated magnetic displacements.

    PubMed

    Ilieva, Mihaela; Bianco, Giuseppe; Åkesson, Susanne

    2016-01-01

    In birds, fat accumulation before and during migration has been shown to be endogenously controlled and tuned by, among other factors, the Earth's magnetic field. However, our knowledge about the influence of the geomagnetic field on the fuelling in migrating birds is still limited to just a few nocturnally migrating passerine species. In order to study if variations of the magnetic field can also influence the fuelling of both day- and night-migrating passerines, we caught first-year dunnocks (Prunella modularis) and subjected them to three magnetic field conditions simulated by a system of magnetic coils: (1) local geomagnetic field of southern Sweden, (2) magnetic field corresponding to the centre of the expected wintering area, and (3) magnetic field met at the northern limit of the species' breeding distribution. We did not find a difference in mass increase between the birds kept in a local magnetic field and a field resembling their wintering area, irrespectively of the mode of magnetic displacement, i.e. direct or step-wise. However, the dunnocks magnetically displaced north showed a lower rate of fuelling in comparison to the control group, probably due to elevated activity. Compared with previous studies, our results suggest that the fuelling response to magnetic displacements during the migration period is specific to the eco-physiological situation. Future studies need to address if there is an effect of magnetic field manipulation on the level of migratory activity in dunnocks and how widespread the influence of local geomagnetic field parameters is on fuelling decisions in different bird species, which have different migratory strategies, distances and migration history. PMID:26883627

  12. Binding of the wheat germ lectin to Cryptococcus neoformans chitooligomers affects multiple mechanisms required for fungal pathogenesis

    PubMed Central

    Fonseca, Fernanda L.; Guimarães, Allan J.; Kmetzsch, Lívia; Dutra, Fabianno F.; Silva, Fernanda D.; Taborda, Carlos P.; Araujo, Glauber de S.; Frases, Susana; Staats, Charley C.; Bozza, Marcelo T.; Schrank, Augusto; Vainstein, Marilene H.; Nimrichter, Leonardo; Casadevall, Arturo; Rodrigues, Marcio L.

    2015-01-01

    The principal capsular component of Cryptococcus neoformans, glucuronoxylomannan (GXM), interacts with surface glycans, including chitin-like oligomers. Although the role of GXM in cryptococcal infection has been well explored, there is no information on how chitooligomers affect fungal pathogenesis. In this study, surface chitooligomers of C. neoformans were blocked through the use of the wheat germ lectin (WGA) and the effects on animal pathogenesis, interaction with host cells, fungal growth and capsule formation were analyzed. Treatment of C. neoformans cells with WGA followed by infection of mice delayed mortality relative to animals infected with untreated fungal cells. This observation was associated with reduced brain colonization by lectin-treated cryptococci. Blocking chitooligomers also rendered yeast cells less efficient in their ability to associate with phagocytes. WGA did not affect fungal viability, but inhibited GXM release to the extracellular space and capsule formation. In WGA-treated yeast cells, genes that are involved in capsule formation and GXM traffic had their transcription levels decreased in comparison with untreated cells. Our results suggest that cellular pathways required for capsule formation and pathogenic mechanisms are affected by blocking chitin-derived structures at the cell surface of C. neoformans. Targeting chitooligomers with specific ligands may reveal new therapeutic alternatives to control cryptococcosis. PMID:23608320

  13. Seed dimorphism, nutrients and salinity differentially affect seed traits of the desert halophyte Suaeda aralocaspica via multiple maternal effects

    PubMed Central

    2012-01-01

    Background Maternal effects may influence a range of seed traits simultaneously and are likely to be context-dependent. Disentangling the interactions of plant phenotype and growth environment on various seed traits is important for understanding regeneration and establishment of species in natural environments. Here, we used the seed-dimorphic plant Suaeda aralocaspica to test the hypothesis that seed traits are regulated by multiple maternal effects. Results Plants grown from brown seeds had a higher brown:black seed ratio than plants from black seeds, and germination percentage of brown seeds was higher than that of black seeds under all conditions tested. However, the coefficient of variation (CV) for size of black seeds was higher than that of brown seeds. Seeds had the smallest CV at low nutrient and high salinity for plants from brown seeds and at low nutrient and low salinity for plants from black seeds. Low levels of nutrients increased size and germinability of black seeds but did not change the seed morph ratio or size and germinability of brown seeds. High levels of salinity decreased seed size but did not change the seed morph ratio. Seeds from high-salinity maternal plants had a higher germination percentage regardless of level of germination salinity. Conclusions Our study supports the multiple maternal effects hypothesis. Seed dimorphism, nutrient and salinity interacted in determining a range of seed traits of S. aralocaspica via bet-hedging and anticipatory maternal effects. This study highlights the importance of examining different maternal factors and various offspring traits in studies that estimate maternal effects on regeneration. PMID:23006315

  14. Biogenic reefs affect multiple components of intertidal soft-bottom benthic assemblages: the Lanice conchilega case study

    NASA Astrophysics Data System (ADS)

    De Smet, Bart; D'Hondt, An-Sofie; Verhelst, Pieterjan; Fournier, Jérôme; Godet, Laurent; Desroy, Nicolas; Rabaut, Marijn; Vincx, Magda; Vanaverbeke, Jan

    2015-01-01

    Biogenic reefs composed of the tube-building polychaete Lanice conchilega are important from a conservation point of view because they noticeably increase the biodiversity in otherwise species poor environments. However, up to now, little or no attention has been paid to the intertidal epi- and hyperbenthic communities associated with the reefs. Therefore, this is the first study which focuses on the effect of L. conchilega reefs on the entire bentho-pelagic community at two different locations. Environmental variables were measured and macro-, epi- and hyperbenthic communities were sampled within a L. conchilega reef and a control area at two locations in France: the bay of the Mont Saint-Michel (BMSM) and Boulogne-sur-Mer (Boulogne). The effect of the reef presence on the benthic community was studied with a 3-factor (Reef, Location and Period) Permanova. In addition, the relationship between the benthic community and the environmental variables was investigated using Distance-based linear models (DistLM). Most collected organisms were sampled in the reef area (macrobenthos: 91%, epibenthos: 81% and hyperbenthos: 78.5%) indicating that, independent of the location, the L. conchilega reefs positively affect all three associated benthic communities. However, the extent of the effect seems to be most pronounced for the macrobenthos and less distinct in case of the hyperbenthos. The macro-, and epibenthos are mainly structured by biotic variables (L. conchilega density and macrobenthic food availability respectively), while the hyperbenthos is rather structured by environmental variables. In general, L. conchilega reefs do not only affect abundances and diversity but they substantially steer the structure of the intertidal benthic sandy beach ecosystem.

  15. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    PubMed

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences. PMID:25224362

  16. Statistical evaluation of biogeochemical variables affecting spatiotemporal distributions of multiple free metal ion concentrations in an urban estuary.

    PubMed

    Dong, Zhao; Lewis, Christopher G; Burgess, Robert M; Coull, Brent; Shine, James P

    2016-05-01

    Free metal ion concentrations have been recognized as a better indicator of metal bioavailability in aquatic environments than total dissolved metal concentrations. However, our understanding of the determinants of free ion concentrations, especially in a metal mixture, is limited, due to underexplored techniques for measuring multiple free metal ions simultaneously. In this work, we performed statistical analyses on a large dataset containing repeated measurements of free ion concentrations of Cu, Zn, Pb, Ni, and Cd, the most commonly measured metals in seawater, at five inshore locations in Boston Harbor, previously collected using an in-situ equilibrium-based multi-metal free ion sampler, the 'Gellyfish'. We examined correlations among these five metals by season, and evaluated effects of 10 biogeochemical variables on free ion concentrations over time and location through multivariate regressions. We also explored potential clustering among the five metals through a principal component analysis. We found significant correlations among metals, with varying patterns over season. Our regression results suggest that instead of dissolved metals, pH, salinity, temperature and rainfall were the most significant determinants of free metal ion concentrations. For example, a one-unit decrease in pH was associated with a 2.2 (Cd) to 99 (Cu) times increase in free ion concentrations. This work is among the first to reveal key contributors to spatiotemporal variations in free ion concentrations, and demonstrated the usefulness of the Gellyfish sampler in routine sampling of free ions within metal mixtures and in generating data for statistical analyses. PMID:26901477

  17. SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency.

    PubMed

    Schlotawa, Lars; Ennemann, Eva Charlotte; Radhakrishnan, Karthikeyan; Schmidt, Bernhard; Chakrapani, Anupam; Christen, Hans-Jürgen; Moser, Hugo; Steinmann, Beat; Dierks, Thomas; Gärtner, Jutta

    2011-03-01

    Multiple Sulfatase Deficiency (MSD) is caused by mutations in the sulfatase-modifying factor 1 gene encoding the formylglycine-generating enzyme (FGE). FGE post translationally activates all newly synthesized sulfatases by generating the catalytic residue formylglycine. Impaired FGE function leads to reduced sulfatase activities. Patients display combined clinical symptoms of single sulfatase deficiencies. For ten MSD patients, we determined the clinical phenotype, FGE expression, localization and stability, as well as residual FGE and sulfatase activities. A neonatal, very severe clinical phenotype resulted from a combination of two nonsense mutations leading to almost fully abrogated FGE activity, highly unstable FGE protein and nearly undetectable sulfatase activities. A late infantile mild phenotype resulted from FGE G263V leading to unstable protein but high residual FGE activity. Other missense mutations resulted in a late infantile severe phenotype because of unstable protein with low residual FGE activity. Patients with identical mutations displayed comparable clinical phenotypes. These data confirm the hypothesis that the phenotypic outcome in MSD depends on both residual FGE activity as well as protein stability. Predicting the clinical course in case of molecularly characterized mutations seems feasible, which will be helpful for genetic counseling and developing therapeutic strategies aiming at enhancement of FGE. PMID:21224894

  18. Target enhancement and distractor inhibition affect transitory surround suppression in dual tasks using multiple rapid serial visual presentation streams.

    PubMed

    Wu, Xia; Greenwood, Pamela; Fu, Shimin

    2016-09-01

    Few studies have investigated the interaction between temporal and spatial dimensions on selective attention using dual tasks in the multiple rapid serial visual presentation (RSVP) paradigm. A phenomenon that the surround suppression in space changes over time (termed transitory surround suppression, TSS, in the present study) has been observed, suggesting the existence of this time-space interaction. However, it is still unclear whether target enhancement or distractor inhibition modulates TSS. Four behavioural experiments were conducted to investigate the mechanism of TSS by manipulating the temporal lag and spatial distance factors between two targets embedded in six RSVP streams. The TSS effect was replicated in a study that eliminated confounds of perceptual effects and attentional switch (Experiment 1). However, the TSS disappeared when two targets shared the same colour in a between-subjects design (Experiment 2a) and a within-subject design (Experiment 2b), suggesting the impact of target enhancement on TSS. Moreover, the TSS was larger for within-category than for between-category distractors (Experiment 3), indicating the impact of distractor inhibition on TSS. These two influences on TSS under different processing demands of target and distractor processing were further confirmed in a skeletal design (Experiment 4). Overall, combinative effects of target enhancement and distractor suppression contribute to the mechanisms of time-space interaction in selective attention during visual search. PMID:26447933

  19. Single-step co-integration of multiple expressible heterologous genes into the ribosomal DNA of the methylotrophic yeast Hansenula polymorpha.

    PubMed

    Klabunde, J; Diesel, A; Waschk, D; Gellissen, G; Hollenberg, C P; Suckow, M

    2002-05-01

    We have investigated the methylotrophic yeast Hansenula polymorpha as a host for the co-integration and expression of multiple heterologous genes using an rDNA integration approach. The ribosomal DNA (rDNA) of H. polymorpha was found to consist of a single rDNA cluster of about 50-60 repeats of an 8-kb unit located on chromosome II. A 2.4-kb segment of H. polymorpha rDNA encompassing parts of the 25S, the complete 5S and the non-transcribed spacer region between 25S and 18S rDNA was isolated and inserted into conventional integrative H. polymorpha plasmids harboring the Saccharomyces- cerevisiae-derived URA3 gene for selection. These rDNA plasmids integrated homologously into the rDNA repeats of a H. polymorpha (odc1) host as several independent clusters. Anticipating that this mode of multiple-cluster integration could be used for the simultaneous integration of several distinct rDNA plasmids, the host strain was co-transformed with a mixture of up to three different plasmids, all bearing the same URA3 selection marker. Transformations indeed resulted in mitotically stable strains harboring one, two, or all three plasmids integrated into the rDNA. The overall copy number of the plasmids integrated did not exceed the number of rDNA repeats present in the untransformed host strain, irrespective of the number of different plasmids involved. Strains harboring different plasmids co-expressed the introduced genes, resulting in functional proteins. Thus, this approach provides a new and attractive tool for the rapid generation of recombinant strains that simultaneously co-produce several proteins in desired stoichiometric ratios. PMID:12021801

  20. Genetic variants in IL2RA and IL7R affect multiple sclerosis disease risk and progression.

    PubMed

    Traboulsee, Anthony L; Bernales, Cecily Q; Ross, Jay P; Lee, Joshua D; Sadovnick, A Dessa; Vilariño-Güell, Carles

    2014-08-01

    Multiple sclerosis (MS) is a common demyelinating neurodegenerative disease with a strong genetic component. Previous studies have associated genetic variants in IL2RA and IL7R in the pathophysiology of the disease. In this study, we describe the association between IL2RA (rs2104286) and IL7R (rs6897932) in the Canadian population. Genotyping 1,978 MS patients and 830 controls failed to identify any significant association between these variants and disease risk. However, stratified analysis for family history of disease and disease course identified a trend towards association for IL2RA in patients without a family history (p = 0.05; odds ratio = 0.77) and a significant association between IL7R and patients who developed progressive MS (PrMS) (p = 0.002; odds ratio = 0.73). Although not statistically significant, the effect of IL2RA (rs2104286) in patients without a family history of MS indicates that the genetic components for familial and sporadic disease are perhaps distinct. This data suggests that the onset of sporadic disease is likely determined by a large number of variants of small effect, whereas MS in patients with a family history of disease is caused by a few deleterious variants. In addition, the significant association between PrMS and rs6897932 indicates that IL7R may not be disease-causing but a determinant of disease course. Further characterization of the effect of IL2RA and IL7R genetic variants in defined MS subtypes is warranted to evaluate the effect of these genes on specific clinical outcomes and to further elucidate the mechanisms of disease onset and progression. PMID:24770783

  1. Calpain Cleaves Most Components in the Multiple Aminoacyl-tRNA Synthetase Complex and Affects Their Functions*

    PubMed Central

    Lei, Hui-Yan; Zhou, Xiao-Long; Ruan, Zhi-Rong; Sun, Wei-Cheng; Eriani, Gilbert; Wang, En-Duo

    2015-01-01

    Nine aminoacyl-tRNA synthetases (aaRSs) and three scaffold proteins form a super multiple aminoacyl-tRNA synthetase complex (MSC) in the human cytoplasm. Domains that have been added progressively to MSC components during evolution are linked by unstructured flexible peptides, producing an elongated and multiarmed MSC structure that is easily attacked by proteases in vivo. A yeast two-hybrid screen for proteins interacting with LeuRS, a representative MSC member, identified calpain 2, a calcium-activated neutral cysteine protease. Calpain 2 and calpain 1 could partially hydrolyze most MSC components to generate specific fragments that resembled those reported previously. The cleavage sites of calpain in ArgRS, GlnRS, and p43 were precisely mapped. After cleavage, their N-terminal regions were removed. Sixty-three amino acid residues were removed from the N terminus of ArgRS to form ArgRSΔN63; GlnRS formed GlnRSΔN198, and p43 formed p43ΔN106. GlnRSΔN198 had a much weaker affinity for its substrates, tRNAGln and glutamine. p43ΔN106 was the same as the previously reported p43-derived apoptosis-released factor. The formation of p43ΔN106 by calpain depended on Ca2+ and could be specifically inhibited by calpeptin and by RNAi of the regulatory subunit of calpain in vivo. These results showed, for the first time, that calpain plays an essential role in dissociating the MSC and might regulate the canonical and non-canonical functions of certain components of the MSC. PMID:26324710

  2. Calpain Cleaves Most Components in the Multiple Aminoacyl-tRNA Synthetase Complex and Affects Their Functions.

    PubMed

    Lei, Hui-Yan; Zhou, Xiao-Long; Ruan, Zhi-Rong; Sun, Wei-Cheng; Eriani, Gilbert; Wang, En-Duo

    2015-10-23

    Nine aminoacyl-tRNA synthetases (aaRSs) and three scaffold proteins form a super multiple aminoacyl-tRNA synthetase complex (MSC) in the human cytoplasm. Domains that have been added progressively to MSC components during evolution are linked by unstructured flexible peptides, producing an elongated and multiarmed MSC structure that is easily attacked by proteases in vivo. A yeast two-hybrid screen for proteins interacting with LeuRS, a representative MSC member, identified calpain 2, a calcium-activated neutral cysteine protease. Calpain 2 and calpain 1 could partially hydrolyze most MSC components to generate specific fragments that resembled those reported previously. The cleavage sites of calpain in ArgRS, GlnRS, and p43 were precisely mapped. After cleavage, their N-terminal regions were removed. Sixty-three amino acid residues were removed from the N terminus of ArgRS to form ArgRSΔN63; GlnRS formed GlnRSΔN198, and p43 formed p43ΔN106. GlnRSΔN198 had a much weaker affinity for its substrates, tRNA(Gln) and glutamine. p43ΔN106 was the same as the previously reported p43-derived apoptosis-released factor. The formation of p43ΔN106 by calpain depended on Ca(2+) and could be specifically inhibited by calpeptin and by RNAi of the regulatory subunit of calpain in vivo. These results showed, for the first time, that calpain plays an essential role in dissociating the MSC and might regulate the canonical and non-canonical functions of certain components of the MSC. PMID:26324710

  3. Vitamin D Status Does Not Affect Disability Progression of Patients with Multiple Sclerosis over Three Year Follow-Up

    PubMed Central

    Smolders, Joost; Rolf, Linda; Klinkenberg, Lieke J. J.; van der Linden, Noreen; Meex, Steven; Damoiseaux, Jan; Hupperts, Raymond

    2016-01-01

    Background and Objective The risk of developing multiple sclerosis (MS) as well as MS disease activity is associated with vitamin D (25(OH)D) status. The relationship between the main functional disability hallmark of MS, disability progression, and 25(OH)D status is less well established though, especially not in MS patients with progressive disease. Methods This retrospective follow-up study included 554 MS patients with a serum baseline 25(OH)D level and Expanded Disability Status Scale (EDSS) with a minimum follow-up of three years. Logistic regressions were performed to assess the effect of baseline 25(OH)D status on relapse rate. Repeated measures linear regression analyses were performed to assess the effect on disability and disability progression. Results Baseline deseasonalized 25(OH)D status was associated with subsequent relapse risk (yes/no), but only in the younger MS patients (≤ 37.5 years; OR = 0.872, per 10 nmol/L 25(OH)D, p = 0.041). Baseline 25(OH)D status was not significantly associated with either disability or disability progression, irrespective of MS phenotype. Conclusion Within the physiological range, 25(OH)D status is just significantly associated with the occurrence of relapses in younger MS patients, but is not associated with disability or disability progression over three years follow-up. Whether high dose supplementation to supra physiological 25(OH)D levels prevents disability progression in MS should become clear from long term follow-up of supplementation studies. PMID:27276080

  4. Multiple Non-Thermal Reaction Steps for the Photooxidation CO to CO2 on Reduced TiO2(110)

    SciTech Connect

    Petrik, Nikolay G.; Kimmel, Gregory A.

    2013-02-07

    The photooxidation of CO on reduced, rutile TiO2(110) was studied on a millisecond timescale. For a saturation coverage of chemisorbed O2 (0sat) and for half that coverage, the CO2 photon-stimulated desorption (PSD) signal is initially zero, increases to a maximum after several tens of milliseconds, and then decreases at longer times. The CO2 PSD signal increases ~5 times more quickly for 0.50sat. The initial rate of increase of the CO2 PSD signal is proportional to the flux of UV photons. The intermediate species involved in the reactions is stable for at least 100 s at 30 K. These results show that two or more non-thermal reaction steps are required to photooxidize CO adsorbed on TiO2(110). In contrast, previous models had suggested that CO photooxidation required only one non-thermal reaction. The likely initial and final charge states of the system suggest that an electron-mediated reaction and a hole-mediated reaction are needed for the complete photooxidation reaction.

  5. Multiple injected and natural conservative tracers quantify mixing in a stream confluence affected by acid mine drainage near Silverton, Colorado

    USGS Publications Warehouse

    Schemel, L.E.; Cox, M.H.; Runkel, R.L.; Kimball, B.A.

    2006-01-01

    The acidic discharge from Cement Creek, containing elevated concentrations of dissolved metals and sulphate, mixed with the circumneutral-pH Animas River over a several hundred metre reach (mixing zone) near Silverton, CO, during this study. Differences in concentrations of Ca, Mg, Si, Sr, and SO42- between the creek and the river were sufficiently large for these analytes to be used as natural tracers in the mixing zone. In addition, a sodium chloride (NaCl) tracer was injected into Cement Creek, which provided a Cl- 'reference' tracer in the mixing zone. Conservative transport of the dissolved metals and sulphate through the mixing zone was verified by mass balances and by linear mixing plots relative to the injected reference tracer. At each of seven sites in the mixing zone, five samples were collected at evenly spaced increments of the observed across-channel gradients, as determined by specific conductance. This created sets of samples that adequately covered the ranges of mixtures (mixing ratios, in terms of the fraction of Animas River water, %AR). Concentrations measured in each mixing zone sample and in the upstream Animas River and Cement Creek were used to compute %AR for the reference and natural tracers. Values of %AR from natural tracers generally showed good agreement with values from the reference tracer, but variability in discharge and end-member concentrations and analytical errors contributed to unexpected outlier values for both injected and natural tracers. The median value (MV) %AR (calculated from all of the tracers) reduced scatter in the mixing plots for the dissolved metals, indicating that the MV estimate reduced the effects of various potential errors that could affect any tracer.

  6. Multiple injected and natural conservative tracers quantify mixing in a stream confluence affected by acid mine drainage near Silverton, Colorado

    NASA Astrophysics Data System (ADS)

    Schemel, Laurence E.; Cox, Marisa H.; Runkel, Robert L.; Kimball, Briant A.

    2006-08-01

    The acidic discharge from Cement Creek, containing elevated concentrations of dissolved metals and sulphate, mixed with the circumneutral-pH Animas River over a several hundred metre reach (mixing zone) near Silverton, CO, during this study. Differences in concentrations of Ca, Mg, Si, Sr, and SO42- between the creek and the river were sufficiently large for these analytes to be used as natural tracers in the mixing zone. In addition, a sodium chloride (NaCl) tracer was injected into Cement Creek, which provided a Cl- reference tracer in the mixing zone. Conservative transport of the dissolved metals and sulphate through the mixing zone was verified by mass balances and by linear mixing plots relative to the injected reference tracer. At each of seven sites in the mixing zone, five samples were collected at evenly spaced increments of the observed across-channel gradients, as determined by specific conductance. This created sets of samples that adequately covered the ranges of mixtures (mixing ratios, in terms of the fraction of Animas River water, %AR). Concentratis measured in each mixing zone sample and in the upstream Animas River and Cement Creek were used to compute %AR for the reference and natural tracers. Values of %AR from natural tracers generally showed good agreement with values from the reference tracer, but variability in discharge and end-member concentrations and analytical errors contributed to unexpected outlier values for both injected and natural tracers. The median value (MV) %AR (calculated from all of the tracers) reduced scatter in the mixing plots for the dissolved metals, indicating that the MV estimate reduced the effects of various potential errors that could affect any tracer.

  7. Examining the Interplay of Processes Across Multiple Time-Scales: Illustration With the Intraindividual Study of Affect, Health, and Interpersonal Behavior (iSAHIB)

    PubMed Central

    Ram, Nilam; Conroy, David E.; Pincus, Aaron L.; Lorek, Amy; Rebar, Amanda; Roche, Michael J.; Coccia, Michael; Morack, Jennifer; Feldman, Josh; Gerstorf, Denis

    2015-01-01

    Human development is characterized by the complex interplay of processes that manifest at multiple levels of analysis and time-scales. We introduce the Intraindividual Study of Affect, Health and Interpersonal Behavior (iSAHIB) as a model for how multiple time-scale study designs facilitate more precise articulation of developmental theory. Combining age heterogeneity, longitudinal panel, daily diary, and experience sampling protocols, the study made use of smartphone and web-based technologies to obtain intensive longitudinal data from 150 persons age 18–89 years as they completed three 21-day measurement bursts (t = 426 bursts, t = 8,557 days) wherein they provided reports on their social interactions (t = 64,112) as they went about their daily lives. We illustrate how multiple time-scales of data can be used to articulate bioecological models of development and the interplay among more ‘distal’ processes that manifest at ‘slower’ time-scales (e.g., age-related differences and burst-to-burst changes in mental health) and more ‘proximal’ processes that manifest at ‘faster’ time-scales (e.g., changes in context that progress in accordance with the weekly calendar and family influence processes). PMID:26989350

  8. Local Kinetic Measures of Macromolecular Structure Reveal Partitioning Among Multiple Parallel Pathways from the Earliest Steps in the Folding of a Large RNA Molecule

    SciTech Connect

    Laederach,A.; Shcherbakova, I.; Liang, M.; Brenowitz, M.; Altman, R.

    2006-01-01

    from ensembles of local measures that will illuminate the chemical and physical characteristics of each step in the process. The applicability of this analysis approach to other macromolecules is discussed.

  9. Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways

    PubMed Central

    Liu, Dajun; Shang, Huiping; Liu, Ying

    2016-01-01

    Stanniocalcin-1 (STC-1) protects against renal ischemia-reperfusion injury (RIRI). However, the molecular mechanisms remain widely unknown. STC-1 inhibits reactive oxygen species (ROS), whereas most ROS-mediated pathways are associated with ischemic injury. Therefore, to explore the mechanism, the effects of STC-1 on ROS-medicated pathways were studied. Non-traumatic vascular clamps were used to establish RIRI mouse models. The serum levels of STC-1, interleukin-6 (IL-6), interferon (IFN) γ, P53, and capase-3 were measured by ELISA kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by fluorescence spectrofluorometer. All these molecules changed significantly in a RIRI model mouse when compared with those in a sham control. Kidney cells were isolated from sham and model mice. STC-1 was overexpressed or knockout in these kidney cells. The molecules in ROS-medicated pathways were measured by real-time quantitative PCR and Western blot. The results showed that STC-1 is an effective ROS scavenger. The serum levels of STC-1, MDA and SOD activity were increased while the serum levels of IL-6, iIFN-γ, P53, and capase-3 were decreased in a model group when compared with a sham control (p < 0.05). Furthermore, the levels of STC-1,p53, phosphorylated mitogen-activated protein kinase kinase (p-MEKK-1), c-Jun N-terminal kinase (p-JNK), extracellular signal-regulated kinase (p-ERK), IkB kinase (p-IKK), nuclear factor (NF) κB, apoptosis signal-regulating kinase 1 (ASK-1) and caspase-3 changed significantly in kidney cells isolated from a RIRI model when compared to those isolated from a sham control (p < 0.05). Meanwhile, STC-1 overexpression or silence caused significant changes of the levels of these ROS-mediated molecules. Therefore, STC-1 maybe improve anti-inflammation, anti-oxidant and anti-apoptosis activities by affecting ROS-mediated pathways, especially the phospho-modifications of the respective proteins, resulting in the increase of SOD and

  10. Stepped nozzle

    DOEpatents

    Sutton, G.P.

    1998-07-14

    An insert is described which allows a supersonic nozzle of a rocket propulsion system to operate at two or more different nozzle area ratios. This provides an improved vehicle flight performance or increased payload. The insert has significant advantages over existing devices for increasing nozzle area ratios. The insert is temporarily fastened by a simple retaining mechanism to the aft end of the diverging segment of the nozzle and provides for a multi-step variation of nozzle area ratio. When mounted in place, the insert provides the nozzle with a low nozzle area ratio. During flight, the retaining mechanism is released and the insert ejected thereby providing a high nozzle area ratio in the diverging nozzle segment. 5 figs.

  11. Stepped nozzle

    DOEpatents

    Sutton, George P.

    1998-01-01

    An insert which allows a supersonic nozzle of a rocket propulsion system to operate at two or more different nozzle area ratios. This provides an improved vehicle flight performance or increased payload. The insert has significant advantages over existing devices for increasing nozzle area ratios. The insert is temporarily fastened by a simple retaining mechanism to the aft end of the diverging segment of the nozzle and provides for a multi-step variation of nozzle area ratio. When mounted in place, the insert provides the nozzle with a low nozzle area ratio. During flight, the retaining mechanism is released and the insert ejected thereby providing a high nozzle area ratio in the diverging nozzle segment.

  12. Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future

    PubMed Central

    Raphael, Itay; Webb, Johanna; Stuve, Olaf; Haskins, William E.; Forsthuber, Thomas G.

    2015-01-01

    Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) which affects over 2.5 million people worldwide. Although MS has been extensively studied, many challenges still remain in regards to treatment, diagnosis, and prognosis. Typically, prognosis and individual responses to treatment are evaluated by clinical tests such the expanded disability status scale (EDSS), magnetic resonance imaging (MRI), and presence of oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). However, none of these measures correlate strongly with treatment efficacy or disease progression across heterogeneous patient populations and subtypes of MS. Numerous studies over the past decades have attempted to identify sensitive and specific biomarkers for diagnosis, prognosis, and treatment efficacy of MS. The objective of this article is to review and discuss the current literature on body fluid biomarkers in MS, including research on potential biomarker candidates in the areas of microRNA, messenger RNA, lipids, and proteins. PMID:25523168

  13. Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris: A quantitative analysis

    SciTech Connect

    Nie, Lei; Wu, Gang; Zhang, Weiwen

    2006-12-01

    The modest correlation between mRNA expression and protein abundance in large scale datasets is explained in part by experimental challenges, such as technological limitations, and in part by fundamental biological factors in the transcription and translation processes. Among various factors affecting the mRNA-protein correlation, the roles of biological factors related to translation are poorly understood. In this study, using experimental mRNA expression and protein abundance data collected from Desulfovibrio vulgaris by DNA microarray and LC-MS/MS proteomic analysis, we quantitatively examined the effects of several translational-efficiency-related sequence features on mRNA-protein correlation. Three classes of sequence features were investigated according to different translational stages: (1) initiation: Shine-Dalgarno sequences, start codon identity and start codon context; (2) elongation: codon usage and amino acid usage; and (3) termination: stop codon identity and stop codon context. Surprisingly, although it is widely accepted that translation initiation is a rate-limiting step for translation, our results showed that the mRNA-protein correlation was affected the most by the features at elongation stages, codon usage and amino acid composition (7.4-12.6% and 5.3-9.3% of the total variation of mRNA-protein correlation, respectively), followed by stop codon context and the Shine-Dalgarno sequence (2.5-4.2% and 2.3%, respectively). Taken together, all sequence features contributed to 18.4-21.8% of the total variation of mRNA-protein correlation. As the first comprehensive quantitative analysis of the mRNA-protein correlation in bacterial D. vulgaris, our results suggest that the traditional view of the relative importance of various sequence features in prokaryotic protein translation might be questionable.

  14. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the ... and your body, leading to the symptoms of MS. They can include Visual disturbances Muscle weakness Trouble ...

  15. Spin-orbit interaction in multiple quantum wells

    SciTech Connect

    Hao, Ya-Fei

    2015-01-07

    In this paper, we investigate how the structure of multiple quantum wells affects spin-orbit interactions. To increase the interface-related Rashba spin splitting and the strength of the interface-related Rashba spin-orbit interaction, we designed three kinds of multiple quantum wells. We demonstrate that the structure of the multiple quantum wells strongly affected the interface-related Rashba spin-orbit interaction, increasing the interface-related Rashba spin splitting to up to 26% larger in multiple quantum wells than in a stepped quantum well. We also show that the cubic Dresselhaus spin-orbit interaction similarly influenced the spin relaxation time of multiple quantum wells and that of a stepped quantum well. The increase in the interface-related Rashba spin splitting originates from the relationship between interface-related Rashba spin splitting and electron probability density. Our results suggest that multiple quantum wells can be good candidates for spintronic devices.

  16. Progression, Symptoms and Psychosocial Concerns among Those Severely Affected by Multiple Sclerosis: A Mixed-Methods Cross-Sectional Study of Black Caribbean and White British People

    PubMed Central

    Koffman, Jonathan; Gao, Wei; Goddard, Cassie; Burman, Rachel; Jackson, Diana; Shaw, Pauline; Barnes, Fiona; Silber, Eli; Higginson, Irene J.

    2013-01-01

    Objective Multiple sclerosis is now more common among minority ethnic groups in the UK but little is known about their experiences, especially in advanced stages. We examine disease progression, symptoms and psychosocial concerns among Black Caribbean (BC) and White British (WB) people severely affected by MS. Design Mixed methods study of 43 BC and 43 WB people with MS (PwMS) with an Expanded Disability Status Scale (EDSS) ≥6 involving data from in clinical records, face-to-face structured interviews and a nested-qualitative component. Progression Index (PI) and Multiple Sclerosis Severity Score (MSSS) were calculated. To control for selection bias, propensity scores were derived for each patient and adjusted for in the comparative statistical analysis; qualitative data were analysed using the framework approach. Results Median EDSS for both groups was (6.5; range: 6.0–9.0). Progression Index (PI) and Multiple Sclerosis Severity Score (MSSS) based on neurological assessment of current EDSS scores identified BC PwMS were more likely to have aggressive disease (PI F = 4.04, p = 0.048, MSSS F = 10.30, p<0.001). Patients’ reports of the time required to reach levels of functional decline equivalent to different EDSS levels varied by group; EDSS 4: BC 2.7 years v/s WB 10.2 years (U = 258.50, p = 0.013), EDSS 6∶6.1 years BC v/s WB 12.7 years (U = 535.500, p = 0.011), EDSS 8: BC 8.7 years v/s WB 10.2 years. Both groups reported high symptom burden. BC PwMS were more cognitively impaired than WB PwMS (F = 9.65, p = 0.003). Thematic analysis of qualitative interviews provides correspondence with quantitative findings; more BC than WB PwMS referred to feelings of extreme frustration and unresolved loss/confusion associated with their rapidly advancing disease. The interviews also reveal the centrality, meanings and impact of common MS-related symptoms. Conclusions Delays in diagnosis should be avoided and more frequent reviews may

  17. Sticky steps inhibit step motions near equilibrium

    NASA Astrophysics Data System (ADS)

    Akutsu, Noriko

    2012-12-01

    Using a Monte Carlo method on a lattice model of a vicinal surface with a point-contact-type step-step attraction, we show that, at low temperature and near equilibrium, there is an inhibition of the motion of macrosteps. This inhibition leads to a pinning of steps without defects, adsorbates, or impurities (self-pinning of steps). We show that this inhibition of the macrostep motion is caused by faceted steps, which are macrosteps that have a smooth side surface. The faceted steps result from discontinuities in the anisotropic surface tension (the surface free energy per area). The discontinuities are brought into the surface tension by the point-contact-type step-step attraction. The point-contact-type step-step attraction also originates “step droplets,” which are locally merged steps, at higher temperatures. We derive an analytic equation of the surface stiffness tensor for the vicinal surface around the (001) surface. Using the surface stiffness tensor, we show that step droplets roughen the vicinal surface. Contrary to what we expected, the step droplets slow down the step velocity due to the diminishment of kinks in the merged steps (smoothing of the merged steps).

  18. Arabidopsis Chloroplast RNA Binding Proteins CP31A and CP29A Associate with Large Transcript Pools and Confer Cold Stress Tolerance by Influencing Multiple Chloroplast RNA Processing Steps[W

    PubMed Central

    Kupsch, Christiane; Ruwe, Hannes; Gusewski, Sandra; Tillich, Michael; Small, Ian; Schmitz-Linneweber, Christian

    2012-01-01

    Chloroplast RNA metabolism is mediated by a multitude of nuclear encoded factors, many of which are highly specific for individual RNA processing events. In addition, a family of chloroplast ribonucleoproteins (cpRNPs) has been suspected to regulate larger sets of chloroplast transcripts. This together with their propensity for posttranslational modifications in response to external cues suggested a potential role of cpRNPs in the signal-dependent coregulation of chloroplast genes. We show here on a transcriptome-wide scale that the Arabidopsis thaliana cpRNPs CP31A and CP29A (for 31 kD and 29 kD chloroplast protein, respectively), associate with large, overlapping sets of chloroplast transcripts. We demonstrate that both proteins are essential for resistance of chloroplast development to cold stress. They are required to guarantee transcript stability of numerous mRNAs at low temperatures and under these conditions also support specific processing steps. Fine mapping of cpRNP–RNA interactions in vivo suggests multiple points of contact between these proteins and their RNA ligands. For CP31A, we demonstrate an essential function in stabilizing sense and antisense transcripts that span the border of the small single copy region and the inverted repeat of the chloroplast genome. CP31A associates with the common 3′-terminus of these RNAs and protects them against 3′-exonucleolytic activity. PMID:23110894

  19. Leidenfrost Drop on a Step

    NASA Astrophysics Data System (ADS)

    Lagubeau, Guillaume; Le Merrer, Marie; Clanet, Christophe; Quere, David

    2008-11-01

    When deposited on a hot plate, a water droplet evaporates quickly. However, a vapor film appears under the drop above a critical temperature, called Leidenfrost temperature, which insulates the drop from its substrate. Linke & al (2006) reported a spontaneous movement of such a drop, when deposited on a ratchet. We study here the case of a flat substrate decorated with a single micrometric step. The drop is deposited on the lower part of the plate and pushed towards the step at small constant velocity. If the kinetic energy of the drop is sufficient, it can climb up the step. In that case, depending on the substrate temperature, the drop can either be decelerated or accelerated by the step. We try to understand the dynamics of these drops, especially the regime where they accelerate. Taking advantage of this phenomenon, we could then build a multiple-step setup, making it possible for a Leidenfrost drop to climb stairs.

  20. c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points

    PubMed Central

    Mateyak, Maria K.; Obaya, Alvaro J.; Sedivy, John M.

    1999-01-01

    c-myc is a cellular proto-oncogene associated with a variety of human cancers and is strongly implicated in the control of cellular proliferation, programmed cell death, and differentiation. We have previously reported the first isolation of a c-myc-null cell line. Loss of c-Myc causes a profound growth defect manifested by the lengthening of both the G1 and G2 phases of the cell cycle. To gain a clearer understanding of the role of c-Myc in cellular proliferation, we have performed a comprehensive analysis of the components that regulate cell cycle progression. The largest defect observed in c-myc−/− cells is a 12-fold reduction in the activity of cyclin D1-Cdk4 and -Cdk6 complexes during the G0-to-S transition. Downstream events, such as activation of cyclin E-Cdk2 and cyclin A-Cdk2 complexes, are delayed and reduced in magnitude. However, it is clear that c-Myc affects the cell cycle at multiple independent points, because restoration of the Cdk4 and -6 defect does not significantly increase growth rate. In exponentially cycling cells the absence of c-Myc reduces coordinately the activities of all cyclin–cyclin-dependent kinase complexes. An analysis of cyclin-dependent kinase complex regulators revealed increased expression of p27KIP1 and decreased expression of Cdk7 in c-myc−/− cells. We propose that c-Myc functions as a crucial link in the coordinate adjustment of growth rate to environmental conditions. PMID:10373516

  1. Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model

    PubMed Central

    2014-01-01

    Multiple sclerosis (MS) is characterized by central nervous system (CNS) inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine for CXCR3+ T cells, is known to regulate T cell differentiation and migration in the periphery, but effects of CXCL10 produced endogenously in the CNS on immune cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial CXCL10 synthesis. These mice, and littermate controls, were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) to induce experimental autoimmune encephalomyelitis (EAE). In comparison to the control mice, spinal cord CXCL10 mRNA and protein were sharply diminished in the mGFAPcre/CXCL10fl/fl EAE mice, confirming that astroglia are chiefly responsible for EAE-induced CNS CXCL10 synthesis. Astroglial CXCL10 deletion did not significantly alter the overall composition of CD4+ lymphocytes and CD11b+ cells in the acutely inflamed CNS, but did diminish accumulation of CD4+ lymphocytes in the spinal cord perivascular spaces. Furthermore, IBA1+ microglia/macrophage accumulation within the lesions was not affected by CXCL10 deletion. Clinical deficits were milder and acute demyelination was substantially reduced in the astroglial CXCL10-deleted EAE mice, but long-term axon loss was equally severe in the two groups. We concluded that astroglial CXCL10 enhances spinal cord perivascular CD4+ lymphocyte accumulation and acute spinal cord demyelination in MOG peptide EAE, but does not play an important role in progressive axon loss in this MS model. PMID:24924222

  2. Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

    PubMed Central

    Saccone, Nancy L.; Culverhouse, Robert C.; Schwantes-An, Tae-Hwi; Cannon, Dale S.; Chen, Xiangning; Cichon, Sven; Giegling, Ina; Han, Shizhong; Han, Younghun; Keskitalo-Vuokko, Kaisu; Kong, Xiangyang; Landi, Maria Teresa; Ma, Jennie Z.; Short, Susan E.; Stephens, Sarah H.; Stevens, Victoria L.; Sun, Lingwei; Wang, Yufei; Wenzlaff, Angela S.; Aggen, Steven H.; Breslau, Naomi; Broderick, Peter; Chatterjee, Nilanjan; Chen, Jingchun; Heath, Andrew C.; Heliövaara, Markku; Hoft, Nicole R.; Hunter, David J.; Jensen, Majken K.; Martin, Nicholas G.; Montgomery, Grant W.; Niu, Tianhua; Payne, Thomas J.; Peltonen, Leena; Pergadia, Michele L.; Rice, John P.; Sherva, Richard; Spitz, Margaret R.; Sun, Juzhong; Wang, Jen C.; Weiss, Robert B.; Wheeler, William; Witt, Stephanie H.; Yang, Bao-Zhu; Caporaso, Neil E.; Ehringer, Marissa A.; Eisen, Tim; Gapstur, Susan M.; Gelernter, Joel; Houlston, Richard; Kaprio, Jaakko; Kendler, Kenneth S.; Kraft, Peter; Leppert, Mark F.; Li, Ming D.; Madden, Pamela A. F.; Nöthen, Markus M.; Pillai, Sreekumar; Rietschel, Marcella; Rujescu, Dan; Schwartz, Ann; Amos, Christopher I.; Bierut, Laura J.

    2010-01-01

    Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10−35 and <10−8 respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10−6). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10−20) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765

  3. Do Parental Attributions Affect Treatment Outcome in a Parenting Program? An Exploration of the Effects of Parental Attributions in an RCT of Stepping Stones Triple P for the ASD Population

    ERIC Educational Resources Information Center

    Whittingham, Koa; Sofronoff, Kate; Sheffield, Jeanie; Sanders, Matthew R.

    2009-01-01

    This study was conducted in conjunction with a randomised controlled trial of the parenting program Stepping Stones Triple P for parents of children with autism spectrum disorders (ASDs). Fifty-nine families with a child with ASD participated. This study focussed upon the role of parental attributions in predicting treatment outcome. Stepping…

  4. Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue

    PubMed Central

    Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; zur Hausen, Harald

    2014-01-01

    Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients. PMID:25169859

  5. The Effects of the Layoff Process on K-12 Teachers: How Do Multiple Years of Layoff Notices Affect Teacher Attitude, Persistence, and Practice?

    ERIC Educational Resources Information Center

    Mendoza, Cara Ann

    2013-01-01

    This qualitative study examines the effects of multiple years of layoff notices on first- or second-year, K-12 teachers employed in a Northern California, suburban school district in 2008-2009. During years of budget crisis in California, teachers new to the profession experienced ongoing employment uncertainty. This study endeavored to understand…

  6. Novel replication-competent circular DNA molecules from healthy cattle serum and milk and multiple sclerosis-affected human brain tissue.

    PubMed

    Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; Zur Hausen, Harald; de Villiers, Ethel-Michele

    2014-01-01

    Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients. PMID:25169859

  7. Stepping motor controller

    DOEpatents

    Bourret, S.C.; Swansen, J.E.

    1982-07-02

    A stepping motor is microprocessor controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.

  8. Stepping motor controller

    DOEpatents

    Bourret, Steven C.; Swansen, James E.

    1984-01-01

    A stepping motor is microprocessingly controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.

  9. Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model

    PubMed Central

    Xu, Shan; Tian, Yuan; Hu, Yili; Zhang, Nijia; Hu, Sheng; Song, Dandan; Wu, Zhengshun; Wang, Yulan; Cui, Yanfang; Tang, Huiru

    2016-01-01

    The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We found that tumor growth caused significant metabonomic changes in multiple non-involved organ tissues involving numerous metabolic pathways, including glycolysis, TCA cycle and metabolisms of amino acids, fatty acids, choline and nucleic acids. Amongst these, the common effects are enhanced glycolysis and nucleoside/nucleotide metabolisms. These findings provided essential biochemistry information about the effects of tumor growth on the non-involved organs. PMID:27329570

  10. Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model.

    PubMed

    Xu, Shan; Tian, Yuan; Hu, Yili; Zhang, Nijia; Hu, Sheng; Song, Dandan; Wu, Zhengshun; Wang, Yulan; Cui, Yanfang; Tang, Huiru

    2016-01-01

    The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We found that tumor growth caused significant metabonomic changes in multiple non-involved organ tissues involving numerous metabolic pathways, including glycolysis, TCA cycle and metabolisms of amino acids, fatty acids, choline and nucleic acids. Amongst these, the common effects are enhanced glycolysis and nucleoside/nucleotide metabolisms. These findings provided essential biochemistry information about the effects of tumor growth on the non-involved organs. PMID:27329570

  11. Multiple sclerosis - discharge

    MedlinePlus

    Your doctor has told you that you have multiple sclerosis. This disease affects the brain and spinal cord ( ... your doctor may prescribe medicine. Some people with multiple sclerosis need to use a urinary catheter . This is ...

  12. Stance time and step width variability have unique contributing impairments in older persons.

    PubMed

    Brach, Jennifer S; Studenski, Stephanie; Perera, Subashan; VanSwearingen, Jessie M; Newman, Anne B

    2008-04-01

    Gait variability may have multiple causes. We hypothesized that central nervous system (CNS) impairments would affect motor control and be manifested as increased stance time and step length variability, while sensory impairments would affect balance and be manifested as increased step width variability. Older adults (mean+/-standard deviation (S.D.) age=79.4+/-4.1, n=558) from the Pittsburgh site of the Cardiovascular Health Study participated. The S.D. across steps was the indicator of gait variability, determined for three gait measures, step length, stance time and step width, using a computerized walkway. Impairment measures included CNS function (modified mini-mental state examination, Trails A and B, Digit Symbol Substitution, finger tapping), sensory function (lower extremity (LE) vibration, vision), strength (grip strength, repeated chair stands), mood, and LE pain. Linear regression models were fit for the three gait variability characteristics using impairment measures as independent variables, adjusted for age, race, gender, and height. Analyses were repeated stratified by gait speed. All measures of CNS impairment were directly related to stance time variability (p<0.01), with increased CNS impairment associated with increased stance time variability. CNS impairments were not related to step length or width variability. Both sensory impairments were inversely related to step width (p<0.01) but not step length or stance time variability. CNS impairments affected stance time variability especially in slow walkers while sensory impairments affected step width variability in fast walkers. Specific patterns of gait variability may imply different underlying causes. Types of gait variability should be specified. Interventions may be targeted at specific types of gait variability. PMID:17632004

  13. Novel TetR family transcriptional factor regulates expression of multiple transport-related genes and affects rifampicin resistance in Mycobacterium smegmatis

    PubMed Central

    Liu, Huicong; Yang, Min; He, Zheng-Guo

    2016-01-01

    Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5′ end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613, and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance. PMID:27271013

  14. Novel TetR family transcriptional factor regulates expression of multiple transport-related genes and affects rifampicin resistance in Mycobacterium smegmatis.

    PubMed

    Liu, Huicong; Yang, Min; He, Zheng-Guo

    2016-01-01

    Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5' end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613, and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance. PMID:27271013

  15. Steps in Behavior Modividation.

    ERIC Educational Resources Information Center

    Straughan, James H.; And Others

    James H. Straughan lists five steps for modifying target behavior and four steps for working with teachers using behavior modification. Grant Martin and Harold Kunzelmann then outline an instructional program for pinpointing and recording classroom behaviors. (JD)

  16. Stepped Hydraulic Geometry in Stepped Channels

    NASA Astrophysics Data System (ADS)

    Comiti, F.; Cadol, D. D.; Wohl, E.

    2007-12-01

    Steep mountain streams typically present a stepped longitudinal profile. Such stepped channels feature tumbling flow, where hydraulic jumps represent an important source of channel roughness (spill resistance). However, the extent to which spill resistance persists up to high flows has not been ascertained yet, such that a faster, skimming flow has been envisaged to begin at those conditions. In order to analyze the relationship between flow resistance and bed morphology, a mobile bed physical model was developed at Colorado State University (Fort Collins, USA). An 8 m-long, 0.6 m-wide flume tilted at a constant 14% slope was used, testing 2 grain-size mixtures differing only for the largest fraction. Experiments were conducted under clear water conditions. Reach-averaged flow velocity was measured using salt tracers, bed morphology and flow depth by a point gage, and surface grain size using commercial image-analysis software. Starting from an initial plane bed, progressively higher flow rates were used to create different bed structures. After each bed morphology was stable with its forming discharge, lower-than-forming flows were run to build a hydraulic geometry curve. Results show that even though equilibrium slopes ranged from 8.5% to 14%, the reach-averaged flow was always sub-critical. Steps formed through a variety of mechanisms, with immobile clasts playing a dominant role by causing local scouring and/or trapping moving smaller particles. Overall, step height, step pool steepness, relative pool area and volume increased with discharge up to the threshold when the bed approached fully- mobilized conditions. For bed morphologies surpassing a minimum profile roughness, a stepped velocity- discharge relationship is evident, with sharp rises in velocity correlated with the disappearance of rollers in pools at flows approaching the formative discharge for each morphology. Flow resistance exhibits an opposite pattern, with drops in resistance being a function

  17. One Step to Learning.

    ERIC Educational Resources Information Center

    Thornton, Carol A.; And Others

    1980-01-01

    Described are activities and games incorporating a technique of "one step" which is used with children with learning difficulties. The purpose of "one step" is twofold, to minimize difficulties with typical trouble spots and to keep the step size of the instruction small. (Author/TG)

  18. A Step Circuit Program.

    ERIC Educational Resources Information Center

    Herman, Susan

    1995-01-01

    Aerobics instructors can use step aerobics to motivate students. One creative method is to add the step to the circuit workout. By incorporating the step, aerobic instructors can accommodate various fitness levels. The article explains necessary equipment and procedures, describing sample stations for cardiorespiratory fitness, muscular strength,…

  19. Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers

    SciTech Connect

    Holmans, P.; Clayton, D.

    1995-11-01

    In an affected-sib-pair study, the parents are often unavailable for typing, particularly for diseases of late onset. In many cases, however, it is possible to sample unaffected siblings. It is therefore desirable to assess the contribution of such siblings to the power of such a study. The likelihood ratio introduced by Risch and improved by Holmans was extended to incorporate data from unaffected siblings. Tests based on two likelihoods were considered: the full likelihood of the data, based on the identity-by-descent (IBD) sharing states of the entire sibship, and a pseudolikelihood based on the IBD sharing states of the affected pair only, using the unaffected siblings to infer parental genotypes. The latter approach was found to be more powerful, except when penetrance was high. Typing an unaffected sibling, or just one parent, was found to give only a small increase in power except when the PIC of the marker was low. Even then, typing an unaffected relative increased the overall number of individuals that had to be typed to achieve a given power. If there is no highly informative marker locus in the area under study, it may be possible to {open_quotes}build{close_quotes} one by combining the alleles from two or more neighboring tightly linked loci into haplotypes. Typing two loci gave a sizeable power increase over a single locus, but typing further loci gave much smaller gains. Building haplotypes will introduce phase uncertainties, with the result that such a system will yield less power than will a single locus with the same number of alleles. This power loss was small, however, and did not affect the conclusions regarding the worth of typing unaffected relatives. 14 refs., 2 figs., 11 tabs.

  20. A functional variant that affects exon-skipping and protein expression of SP140 as genetic mechanism predisposing to multiple sclerosis.

    PubMed

    Matesanz, Fuencisla; Potenciano, Victor; Fedetz, Maria; Ramos-Mozo, Priscila; Abad-Grau, María del Mar; Karaky, Mohamad; Barrionuevo, Cristina; Izquierdo, Guillermo; Ruiz-Peña, Juan Luis; García-Sánchez, María Isabel; Lucas, Miguel; Fernández, Óscar; Leyva, Laura; Otaegui, David; Muñoz-Culla, Maider; Olascoaga, Javier; Vandenbroeck, Koen; Alloza, Iraide; Astobiza, Ianire; Antigüedad, Alfredo; Villar, Luisa María; Álvarez-Cermeño, José Carlos; Malhotra, Sunny; Comabella, Manuel; Montalban, Xavier; Saiz, Albert; Blanco, Yolanda; Arroyo, Rafael; Varadé, Jezabel; Urcelay, Elena; Alcina, Antonio

    2015-10-01

    Several variants in strong linkage disequilibrium (LD) at the SP140 locus have been associated with multiple sclerosis (MS), Crohn's disease (CD) and chronic lymphocytic leukemia (CLL). To determine the causal polymorphism, we have integrated high-density data sets of expression quantitative trait loci (eQTL), using GEUVADIS RNA sequences and 1000 Genomes genotypes, with MS-risk variants of the high-density Immunochip array performed by the International Multiple Sclerosis Genetic Consortium (IMSGC). The variants most associated with MS were also correlated with a decreased expression of the full-length RNA isoform of SP140 and an increase of an isoform lacking exon 7. By exon splicing assay, we have demonstrated that the rs28445040 variant was the causal factor for skipping of exon 7. Western blots of peripheral blood mononuclear cells from MS patients showed a significant allele-dependent reduction of the SP140 protein expression. To confirm the association of this functional variant with MS and to compare it with the best-associated variant previously reported by GWAS (rs10201872), a case-control study including 4384 MS patients and 3197 controls was performed. Both variants, in strong LD (r(2) = 0.93), were found similarly associated with MS [P-values, odds ratios: 1.9E-9, OR = 1.35 (1.22-1.49) and 4.9E-10, OR = 1.37 (1.24-1.51), respectively]. In conclusion, our data uncover the causal variant for the SP140 locus and the molecular mechanism associated with MS risk. In addition, this study and others previously reported strongly suggest that this functional variant may be shared with other immune-mediated diseases as CD and CLL. PMID:26152201

  1. The Process of Transformation: Steps toward Change.

    ERIC Educational Resources Information Center

    Tarule, Jill Mattuck

    1980-01-01

    A study of adult learners reveals four steps of transformative change in adult life: diffusion, dissonance, differentiation, and coherence. The educational implications of these steps are explored through case studies, and it is argued that these transformative changes affect not only the individual and the nature of adult education, but the…

  2. STEP: A Futurevision, Today

    NASA Technical Reports Server (NTRS)

    1994-01-01

    STEP (STandard for the Exchange of Product Model Data) is an innovative software tool that allows the exchange of data between different programming systems to occur and helps speed up the designing in various process industries. This exchange occurs easily between those companies that have STEP, and many industries and government agencies are requiring that their vendors utilize STEP in their computer aided design projects, such as in the areas of mechanical, aeronautical, and electrical engineering. STEP allows the process of concurrent engineering to occur and increases the quality of the design product. One example of the STEP program is the Boeing 777, the first paperless airplane.

  3. Genetic variation in aldo-keto reductase 1D1 (AKR1D1) affects the expression and activity of multiple cytochrome P450s.

    PubMed

    Chaudhry, Amarjit S; Thirumaran, Ranjit K; Yasuda, Kazuto; Yang, Xia; Fan, Yiping; Strom, Stephen C; Schuetz, Erin G

    2013-08-01

    Human liver gene regulatory (Bayesian) network analysis was previously used to identify a cytochrome P450 (P450) gene subnetwork with Aldo-keto reductase 1D1 (AKR1D1) as a key regulatory driver of this subnetwork. This study assessed the biologic importance of AKR1D1 [a key enzyme in the synthesis of bile acids, ligand activators of farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), known transcriptional regulators of P450s] to hepatic P450 expression. Overexpression of AKR1D1 in primary human hepatocytes led to increased expression of CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2B6. Conversely, AKR1D1 knockdown decreased expression of these P450s. We resequenced AKR1D1 from 98 donor livers and identified a 3'-untranslated region (UTR) (rs1872930) single nucleotide polymorphism (SNP) significantly associated with higher AKR1D1 mRNA expression. AKR1D1 3'-UTR-luciferase reporter studies showed that the variant allele resulted in higher luciferase activity, suggesting that the SNP increases AKR1D1 mRNA stability and/or translation efficiency. Consistent with AKR1D1's putative role as a driver of the P450 subnetwork, the AKR1D1 3'-UTR SNP was significantly associated with increased hepatic mRNA expression of multiple P450s (CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2B6) and CYP3A4, CYP2C8, CYP2C19, and CYP2B6 activities. After adjusting for multiple testing, the association remained significant for AKR1D1, CYP2C9, and CYP2C8 mRNA expression and CYP2C8 activity. These results provide new insights into the variation in expression and activity of P450s that can account for interindividual differences in drug metabolism/efficacy and adverse drug events. In conclusion, we provide the first experimental evidence supporting a role for AKR1D1 as a key genetic regulator of the P450 network. PMID:23704699

  4. Magnetic Resonance Evaluation of Multiple Myeloma at 3.0 Tesla: How Do Bone Marrow Plasma Cell Percentage and Selection of Protocols Affect Lesion Conspicuity?

    PubMed Central

    Takasu, Miyuki; Tamura, Takayuki; Kaichi, Yoko; Tanitame, Keizo; Akiyama, Yuji; Date, Shuji; Sakai, Akira; Kuroda, Yoshiaki; Awai, Kazuo

    2014-01-01

    Purpose To compare various pulse sequences in terms of percent contrast and contrast-to-noise ratio (CNR) for detection of focal multiple myeloma lesions and to assess the dependence of lesion conspicuity on the bone marrow plasma cell percent (BMPC%). Materials and Methods Sagittal T1-weighted FSE, fat-suppressed T2-weighted FSE (FS- T2 FSE), fast STIR and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of the lumbar spine were performed (n = 45). Bone marrow (BM)-focal myeloma lesion percent contrast and CNR were calculated. Spearman rank correlation coefficients were obtained between percent contrast, CNR and BMPC%. Percent contrasts and CNRs were compared among the three imaging sequences. Results BM-focal lesion percent contrasts, CNRs and BMPC% showed significant negative correlations in the three fat-suppression techniques. Percent contrast and CNRs were significantly higher for FS- T2 FSE than for STIR (P<0.01, P<0.05, respectively), but no significant differences were found among the three fat-suppression methods in the low tumor load BM group. Conclusion The higher BMPC% was within BM, the less conspicuous the focal lesion was on fat-suppressed MRI. The most effective protocol for detecting focal lesions was FS- T2 FSE. In the high tumor load BM group, no significant differences in lesion conspicuity were identified among the three fat-suppression techniques. PMID:24489680

  5. The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies.

    PubMed

    McKay, Fiona C; Gatt, Prudence N; Fewings, Nicole; Parnell, Grant P; Schibeci, Stephen D; Basuki, Monica A I; Powell, Joseph E; Goldinger, Anita; Fabis-Pedrini, Marzena J; Kermode, Allan G; Burke, Therese; Vucic, Steve; Stewart, Graeme J; Booth, David R

    2016-02-01

    Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p<0.028 for TBX21) and demonstrate longitudinal stability (p<10(-4)) and high heritability (h(2)=0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate. PMID:26762769

  6. One-step multiple component isolation from the oil of Crinitaria tatarica (Less.) Sojak. by preparative capillary gas with characterization by spectroscopic and spectrometric techniques and evaluation of biological activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present work multiple component isolation from the oil of Crinitaria tatarica (Less.) Sojak. by Preparative Capillary Gas Chromatography (PCGC) with characterization by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have been carried out. Gas chromatography (GC-FID) ...

  7. Cyclic steps on ice

    NASA Astrophysics Data System (ADS)

    Yokokawa, M.; Izumi, N.; Naito, K.; Parker, G.; Yamada, T.; Greve, R.

    2016-05-01

    Boundary waves often form at the interface between ice and fluid flowing adjacent to it, such as ripples under river ice covers, and steps on the bed of supraglacial meltwater channels. They may also be formed by wind, such as the megadunes on the Antarctic ice sheet. Spiral troughs on the polar ice caps of Mars have been interpreted to be cyclic steps formed by katabatic wind blowing over ice. Cyclic steps are relatives of upstream-migrating antidunes. Cyclic step formation on ice is not only a mechanical but also a thermodynamic process. There have been very few studies on the formation of either cyclic steps or upstream-migrating antidunes on ice. In this study, we performed flume experiments to reproduce cyclic steps on ice by flowing water, and found that trains of steps form when the Froude number is larger than unity. The features of those steps allow them to be identified as ice-bed analogs of cyclic steps in alluvial and bedrock rivers. We performed a linear stability analysis and obtained a physical explanation of the formation of upstream-migrating antidunes, i.e., precursors of cyclic steps. We compared the results of experiments with the predictions of the analysis and found the observed steps fall in the range where the analysis predicts interfacial instability. We also found that short antidune-like undulations formed as a precursor to the appearance of well-defined steps. This fact suggests that such antidune-like undulations correspond to the instability predicted by the analysis and are precursors of cyclic steps.

  8. Impact of multiple anthropogenic stressors on freshwater: how do glyphosate and the invasive mussel Limnoperna fortunei affect microbial communities and water quality?

    PubMed

    Pizarro, Haydée; Di Fiori, Eugenia; Sinistro, Rodrigo; Ramírez, Marina; Rodríguez, Patricia; Vinocur, Alicia; Cataldo, Daniel

    2016-01-01

    The study of the joint effect of multiple anthropogenic stressors is important because the emerging consequences are often unpredictable on the basis of knowledge of single effects. We explored the joint impact of glyphosate and the invasive golden mussel Limnoperna fortunei on freshwater phytoplankton, bacterioplankton and periphyton, and on the physical and chemical properties of the water. We manipulated both stressors simultaneously in a 25-day experiment using outdoor mesocosms; we assayed technical-grade glyphosate acid at four concentrations: 0, 1, 3 and 6 mg gly L(−1) under scenarios with and without mussels. The addition of the glyphosate significantly increased total phosphorus according to the concentration used; the high clearance rate of L. fortunei significantly decreased phytoplanktonic abundance leading to low values of turbidity. The mussel significantly stimulated the development of filamentous green algae (metaphyton). Interestingly, the combined effect revealed that L. fortunei accelerated the dissipation of glyphosate, which showed a 4-fold decrease in its half-life; this promoted the rapid bioavailability of glyphosate-derived phosphorus in the water. The interaction had a synergistic effect on soluble reactive phosphorus concentrations and was directly dependent on the concentration of glyphosate. A synergistic effect was also observed on bacterioplankton, water turbidity and metaphyton, thus inducing enhanced and rapid eutrophication. The ability of mussels to reduce glyphosate in water may be valued as positive, but our results allow us to predict that the invasion of Limnoperna fortunei in natural freshwater systems contaminated by glyphosate will accelerate the negative impact of the herbicide associated with eutrophication. PMID:26467805

  9. From raw material to dish: pasta quality step by step.

    PubMed

    Sicignano, Angelo; Di Monaco, Rossella; Masi, Paolo; Cavella, Silvana

    2015-10-01

    Pasta is a traditional Italian cereal-based food that is popular worldwide because of its convenience, versatility, sensory and nutritional value. The aim of this review is to present a step-by-step guide to facilitate the understanding of the most important events that can affect pasta characteristics, directing the reader to the appropriate production steps. Owing to its unique flavor, color, composition and rheological properties, durum wheat semolina is the best raw material for pasta production. Although pasta is traditionally made from only two ingredients, sensory quality and chemical/physical characteristics of the final product may vary greatly. Starting from the same ingredients, there are a lot of different events in each step of pasta production that can result in the development of varieties of pasta with different characteristics. In particular, numerous studies have demonstrated the importance of temperature and humidity conditions of the pasta drying operation as well as the significance of the choice of raw material and operating conditions on pasta quality. PMID:25783568

  10. Atomic Scale Transport in Graphene on Stepped SiC(0001) Surfaces

    NASA Astrophysics Data System (ADS)

    Ji, Shuaihua; Hannon, James B.; Tromp, Ruud M.; Ellis, Arthur W.; Reuter, Mark C.; Ross, Frances M.

    2011-03-01

    Thermal decomposition of SiC is a promising route to wafer-scale epitaxial graphene. However, the initial SiC surface contains steps, and graphene formation induces additional steps. Here we consider how these steps affect current transport in graphene. 1-2ML graphene was grown by annealing SiC above 1300circ; C in disilane. Low energy electron microscopy was used to determine graphene thickness, and transport through 1ML thick regions was measured by scanning tunneling potentiometry. In this technique a bias is applied between two fixed probes while a third, scanning probe measures the local electrochemical potential as well as topography. This allows us to determine the resistivity of the graphene sheet on terraces and across substrate steps. Single steps with 0.5nm height show very weak scattering. However, multiple steps of height 1.0 and 1.5nm scatter strongly, exhibiting a potential drop equivalent to ~ 80 nm and 120nm respectively of terrace graphene. Thus, step bunching is important, and steps separated by less than a few hundred nm can dominate transport through a graphene sheet.

  11. The CORE study protocol: a stepped wedge cluster randomised controlled trial to test a co-design technique to optimise psychosocial recovery outcomes for people affected by mental illness in the community mental health setting

    PubMed Central

    Palmer, Victoria J; Chondros, Patty; Piper, Donella; Callander, Rosemary; Weavell, Wayne; Godbee, Kali; Potiriadis, Maria; Richard, Lauralie; Densely, Konstancja; Herrman, Helen; Furler, John; Pierce, David; Schuster, Tibor; Iedema, Rick; Gunn, Jane

    2015-01-01

    Introduction User engagement in mental health service design is heralded as integral to health systems quality and performance, but does engagement improve health outcomes? This article describes the CORE study protocol, a novel stepped wedge cluster randomised controlled trial (SWCRCT) to improve psychosocial recovery outcomes for people with severe mental illness. Methods An SWCRCT with a nested process evaluation will be conducted over nearly 4 years in Victoria, Australia. 11 teams from four mental health service providers will be randomly allocated to one of three dates 9 months apart to start the intervention. The intervention, a modified version of Mental Health Experience Co-Design (MH ECO), will be delivered to 30 service users, 30 carers and 10 staff in each cluster. Outcome data will be collected at baseline (6 months) and at completion of each intervention wave. The primary outcome is improvement in recovery score using the 24-item Revised Recovery Assessment Scale for service users. Secondary outcomes are improvements to user and carer mental health and well-being using the shortened 8-item version of the WHOQOL Quality of Life scale (EUROHIS), changes to staff attitudes using the 19-item Staff Attitudes to Recovery Scale and recovery orientation of services using the 36-item Recovery Self Assessment Scale (provider version). Intervention and usual care periods will be compared using a linear mixed effects model for continuous outcomes and a generalised linear mixed effects model for binary outcomes. Participants will be analysed in the group that the cluster was assigned to at each time point. Ethics and dissemination The University of Melbourne, Human Research Ethics Committee (1340299.3) and the Federal and State Departments of Health Committees (Project 20/2014) granted ethics approval. Baseline data results will be reported in 2015 and outcomes data in 2017. Trial registration number Australian and New Zealand Clinical Trials Registry ACTRN

  12. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion

    PubMed Central

    Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Raymond, F Lucy; Linglart, Agnès; Jüppner, Harald

    2016-01-01

    Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright’s Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but

  13. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion.

    PubMed

    Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Raymond, F Lucy; Linglart, Agnès; Jüppner, Harald

    2016-04-01

    Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but it

  14. Is environmental radon gas associated with the incidence of neurodegenerative conditions? A retrospective study of multiple sclerosis in radon affected areas in England and Wales.

    PubMed

    Groves-Kirkby, Christopher J; Denman, Antony R; Campbell, Jackie; Crockett, Robin G M; Phillips, Paul S; Rogers, Stephen

    2016-04-01

    To test whether an association exists between radon gas concentration in the home and increased multiple sclerosis (MS) incidence, a retrospective study was undertaken of MS incidence in known areas of raised domestic radon concentration in England and Wales, using The Health Improvement Network (THIN) clinical research database. The study population comprised 20,140,498 person-years of clinical monitoring (males: 10,056,628: 49.93%; females: 10,083,870: 50.07%), representing a mean annual population of 2.5 million individuals. To allow for the possible latency of MS initiation following exposure, data extraction was limited to patients with at least five years registration history with the same GP practice before first diagnosis. Patient records were allocated to one of nine radon concentration bands depending on the average radon level in their postcode sector. MS incidence was analysed by searching for patients with first MS diagnosis over the eight calendar years 2005-2012 inclusive. 1512 new MS cases were diagnosed, 1070 females, 442 males, equivalent to raw incidence rates of 7.51, 10.61 and 4.40 per 10(5) person-years respectively, comparable to previously reported results. Of these new cases, 115 could be allocated to one of the radon bands representing high radon areas. Standardising to the UK 2010 population, excess relative risk (ERR) figures for MS were calculated for each radon band. Linear regression of ERR against mean band radon concentration shows a positive gradient of 0.22 per 100 Bq·m(-3) (R(2) = 0.25, p = 0.0961) when forced through the origin to represent a linear-no-threshold response. The null hypothesis falls inside the 95% confidence interval for the linear fit and therefore this fit is not statistically significant. We conclude that, despite THIN sampling around 5% of the population, insufficient data was available to confirm or refute the hypothesised association between MS incidence and radon concentration. PMID:26809141

  15. Golgi-Cox Staining Step by Step

    PubMed Central

    Zaqout, Sami; Kaindl, Angela M.

    2016-01-01

    Golgi staining remains a key method to study neuronal morphology in vivo. Since most protocols delineating modifications of the original staining method lack details on critical steps, establishing this method in a laboratory can be time-consuming and frustrating. Here, we describe the Golgi-Cox staining in such detail that should turn the staining into an easily feasible method for all scientists working in the neuroscience field. PMID:27065817

  16. Structure/Function Studies Involving the V3 Region of the HIV-1 Envelope Delineate Multiple Factors That Affect Neutralization Sensitivity

    PubMed Central

    Cohen, Sandra Sharpe; Boyd, David; Kong, Xiang-Peng; Seaman, Michael; Nussenzweig, Michel; Klein, Florian; Overbaugh, Julie; Totrov, Max

    2015-01-01

    ABSTRACT Antibodies (Abs) specific for the V3 loop of the HIV-1 gp120 envelope neutralize most tier 1 and many tier 2 viruses and are present in essentially all HIV-infected individuals as well as immunized humans and animals. Vaccine-induced V3 Abs are associated with reduced HIV infection rates in humans and affect the nature of transmitted viruses in infected vaccinees, despite the fact that V3 is often occluded in the envelope trimer. Here, we link structural and experimental data showing how conformational alterations of the envelope trimer render viruses exceptionally sensitive to V3 Abs. The experiments interrogated the neutralization sensitivity of pseudoviruses with single amino acid mutations in various regions of gp120 that were predicted to alter packing of the V3 loop in the Env trimer. The results indicate that the V3 loop is metastable in the envelope trimer on the virion surface, flickering between states in which V3 is either occluded or available for binding to chemokine receptors (leading to infection) and to V3 Abs (leading to virus neutralization). The spring-loaded V3 in the envelope trimer is easily released by disruption of the stability of the V3 pocket in the unliganded trimer or disruption of favorable V3/pocket interactions. Formation of the V3 pocket requires appropriate positioning of the V1V2 domain, which is, in turn, dependent on the conformation of the bridging sheet and on the stability of the V1V2 B-C strand-connecting loop. IMPORTANCE The levels of antibodies to the third variable region (V3) of the HIV envelope protein correlate with reduced HIV infection rates. Previous studies showed that V3 is often occluded, as it sits in a pocket of the envelope trimer on the surface of virions; however, the trimer is flexible, allowing occluded portions of the envelope (like V3) to flicker into an exposed position that binds antibodies. Here we provide a systematic interrogation of mechanisms by which single amino acid changes in various

  17. The Twelve Steps Experientially.

    ERIC Educational Resources Information Center

    Horne, Lianne

    Experiential activities provide each participant with the ability to see, feel, and experience whatever therapeutic issue the facilitator is addressing, and usually much more. This paper presents experiential activities to address the 12 steps of recovery adopted from Alcoholics Anonymous. These 12 steps are used worldwide for many other recovery…

  18. STEP Experiment Requirements

    NASA Technical Reports Server (NTRS)

    Brumfield, M. L. (Compiler)

    1984-01-01

    A plan to develop a space technology experiments platform (STEP) was examined. NASA Langley Research Center held a STEP Experiment Requirements Workshop on June 29 and 30 and July 1, 1983, at which experiment proposers were invited to present more detailed information on their experiment concept and requirements. A feasibility and preliminary definition study was conducted and the preliminary definition of STEP capabilities and experiment concepts and expected requirements for support services are presented. The preliminary definition of STEP capabilities based on detailed review of potential experiment requirements is investigated. Topics discussed include: Shuttle on-orbit dynamics; effects of the space environment on damping materials; erectable beam experiment; technology for development of very large solar array deployers; thermal energy management process experiment; photovoltaic concentrater pointing dynamics and plasma interactions; vibration isolation technology; flight tests of a synthetic aperture radar antenna with use of STEP.

  19. Multiple sclerosis.

    PubMed

    Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

    2015-06-01

    Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. PMID:25979578

  20. Integrated Marketing for Colleges, Universities, and Schools: A Step-by-Step Planning Guide.

    ERIC Educational Resources Information Center

    Sevier, Robert A.

    This book offers a step-by-step approach to marketing for educational institutions, especially colleges and universities. The book is organized into three broad sections. Section 1 makes the case for marketing in six chapters which address: (1) challenges which are or will affect colleges and universities; (2) the role of institutional mission,…

  1. The Next Giant Step

    NASA Video Gallery

    Artist Robert McCall painted "The Next Giant Step" in 1979 to commemorate the heroism and courage of spaceflight pioneers. Located in the lobby of Johnson's building 2, the mural depicts America's ...

  2. Social embodiment in directional stepping behavior.

    PubMed

    Stins, John F; Lobel, Adam; Roelofs, Karin; Beek, Peter J

    2014-08-01

    Embodiment theories emphasize the role played by sensory and motor processes in psychological states, such as social information processing. Motivated by this idea, we examined how whole-body postural behaviors couple to social affective cues, viz., pictures of smiling and angry faces. We adopted a Simon-like paradigm, whereby healthy female volunteers were asked to select and initiate a forward or backward step on a force plate in response to the gender of the poser (male/female), regardless of emotion. Detailed analysis of the spatiotemporal unfolding of the body center of pressure during the steps revealed that task-irrelevant emotion had no effect on the initiation times of the steps, i.e., there was no evidence of an affective Simon effect. An unexpected finding was that steps were initiated relatively slow in response to female angry faces. This Stroop-like effect suggests that postural behavior is influenced by whether certain stimulus features match or mismatch. PMID:24362584

  3. Multilevel factors affecting quality: examples from the cancer care continuum.

    PubMed

    Zapka, Jane; Taplin, Stephen H; Ganz, Patricia; Grunfeld, Eva; Sterba, Katherine

    2012-05-01

    The complex environmental context must be considered as we move forward to improve cancer care and, ultimately, patient and population outcomes. The cancer care continuum represents several care types, each of which includes multiple technical and communication steps and interfaces among patients, providers, and organizations. We use two case scenarios to 1) illustrate the variability, diversity, and interaction of factors from multiple levels that affect care quality and 2) discuss research implications and provide hypothetical examples of multilevel interventions. Each scenario includes a targeted literature review to illustrate contextual influences upon care and sets the stage for theory-informed interventions. The screening case highlights access issues in older women, and the survivorship case illustrates the multiple transition challenges faced by patients, families, and organizations. Example interventions show the potential gains of implementing intervention strategies that work synergistically at multiple levels. While research examining multilevel intervention is a priority, it presents numerous study design, measurement, and analytic challenges. PMID:22623591

  4. DNA INTERSTRAND CROSSLINK REPAIR IN MAMMALIAN CELLS: STEP BY STEP

    PubMed Central

    Muniandy, Parameswary; Liu, Jia; Majumdar, Alokes; Liu, Su-ting; Seidman, Michael M.

    2009-01-01

    Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair scheme involving incisions on one strand on either side of the ICL (unhooking) producing a gapped intermediate with the incised oligonucleotide attached to the intact strand. The gap is filled by recombinational repair or lesion bypass synthesis. The remaining monoadduct is then removed by Nucleotide Excision Repair (NER). Despite considerable effort, our understanding of each step in mammalian cells is still quite limited. In part this reflects the variety of crosslinking compounds, each with distinct structural features, used by different investigators. Also, multiple repair pathways are involved, variably operative during the cell cycle. G1 phase repair requires functions from NER, although the mechanism of recognition has not been determined. Repair can be initiated by encounters with the transcriptional apparatus, or a replication fork. In the case of the latter, the reconstruction of a replication fork, stalled or broken by collision with an ICL, adds to the complexity of the repair process. The enzymology of unhooking, the identity of the lesion bypass polymerases required to fill the first repair gap, and the functions involved in the second repair cycle are all subjects of active inquiry. Here we will review current understanding of each step in ICL repair in mammalian cells. PMID:20039786

  5. Stepped inlet optical panel

    DOEpatents

    Veligdan, James T.

    2001-01-01

    An optical panel includes stacked optical waveguides having stepped inlet facets collectively defining an inlet face for receiving image light, and having beveled outlet faces collectively defining a display screen for displaying the image light channeled through the waveguides by internal reflection.

  6. Steps Toward Effective Assessment.

    ERIC Educational Resources Information Center

    Cope, Carolyn O.

    1996-01-01

    Describes and defines the steps involved in measurement and evaluation: (1) determining an outcome; (2)defining scoring criteria; (3)establishing appropriate assessment tasks; and (4)creating opportunities for learning. Includes a flow chart for a design-down curriculum and an example of a vocal performance rating scale assessment. (MJP)

  7. Primary Amyloidosis Presenting as Upper Limb Multiple Mononeuropathies

    PubMed Central

    Tracy, Jennifer A.; Dyck, Peter J.; Dyck, P. James B.

    2010-01-01

    Peripheral neuropathy in primary (AL) amyloidosis is usually lower limb predominant, length-dependent, symmetrical, and affects small (pain and autonomic) fibers, as much or more than large fibers. We report a patient with step-wise progressive, multiple upper limb mononeuropathies that were due to nerve biopsy-proven primary amyloidosis (lambda light chain), with no systemic or autonomic features. Recognition that light chain amyloidosis may be the cause of a multiple mononeuropathy pattern adds to the differential diagnosis of this clinical phenotype. PMID:20405503

  8. In vitro and in vivo single myosin step-sizes in striated muscle.

    PubMed

    Burghardt, Thomas P; Sun, Xiaojing; Wang, Yihua; Ajtai, Katalin

    2015-12-01

    Myosin in muscle transduces ATP free energy into the mechanical work of moving actin. It has a motor domain transducer containing ATP and actin binding sites, and, mechanical elements coupling motor impulse to the myosin filament backbone providing transduction/mechanical-coupling. The mechanical coupler is a lever-arm stabilized by bound essential and regulatory light chains. The lever-arm rotates cyclically to impel bound filamentous actin. Linear actin displacement due to lever-arm rotation is the myosin step-size. A high-throughput quantum dot labeled actin in vitro motility assay (Qdot assay) measures motor step-size in the context of an ensemble of actomyosin interactions. The ensemble context imposes a constant velocity constraint for myosins interacting with one actin filament. In a cardiac myosin producing multiple step-sizes, a "second characterization" is step-frequency that adjusts longer step-size to lower frequency maintaining a linear actin velocity identical to that from a shorter step-size and higher frequency actomyosin cycle. The step-frequency characteristic involves and integrates myosin enzyme kinetics, mechanical strain, and other ensemble affected characteristics. The high-throughput Qdot assay suits a new paradigm calling for wide surveillance of the vast number of disease or aging relevant myosin isoforms that contrasts with the alternative model calling for exhaustive research on a tiny subset myosin forms. The zebrafish embryo assay (Z assay) performs single myosin step-size and step-frequency assaying in vivo combining single myosin mechanical and whole muscle physiological characterizations in one model organism. The Qdot and Z assays cover "bottom-up" and "top-down" assaying of myosin characteristics. PMID:26728749

  9. Micromachine Wedge Stepping Motor

    SciTech Connect

    Allen, J.J.; Schriner, H.K.

    1998-11-04

    A wedge stepping motor, which will index a mechanism, has been designed and fabricated in the surface rnicromachine SUMMiT process. This device has demonstrated the ability to index one gear tooth at a time with speeds up to 205 teeth/see. The wedge stepper motor has the following features, whi:h will be useful in a number of applications. o The ability to precisely position mechanical components. . Simple pulse signals can be used for operation. o Only 2 drive signals are requixed for operation. o Torque and precision capabilities increase with device size . The device to be indexed is restrained at all times by the wedge shaped tooth that is used for actuation. This paper will discuss the theory of operation and desi=m of the wedge stepping motor. The fabrication and testing of I he device will also be presented.

  10. Stepping up with Pedometers

    ERIC Educational Resources Information Center

    Cagle, Bart

    2004-01-01

    Physical educators are using technology more than ever to help meet the national standards in physical education. One of the more useful technological tools is the digital pedometer. The newer versions of pedometers have multiple functions. They record the time elapsed, distance traveled and speed, and pulse rate. Others are equipped with a melody…

  11. Gene Set Analysis: A Step-By-Step Guide

    PubMed Central

    Mooney, Michael A.; Wilmot, Beth

    2015-01-01

    To maximize the potential of genome-wide association studies, many researchers are performing secondary analyses to identify sets of genes jointly associated with the trait of interest. Although methods for gene-set analyses (GSA), also called pathway analyses, have been around for more than a decade, the field is still evolving. There are numerous algorithms available for testing the cumulative effect of multiple SNPs, yet no real consensus in the field about the best way to perform a GSA. This paper provides an overview of the factors that can affect the results of a GSA, the lessons learned from past studies, and suggestions for how to make analysis choices that are most appropriate for different types of data. PMID:26059482

  12. Multiple steps control immunity during the intracellular accommodation of rhizobia

    PubMed Central

    Berrabah, Fathi; Ratet, Pascal; Gourion, Benjamin

    2015-01-01

    Medicago truncatula belongs to the legume family and forms symbiotic associations with nitrogen fixing bacteria, the rhizobia. During these interactions, the plants develop root nodules in which bacteria invade the plant cells and fix nitrogen for the benefit of the plant. Despite massive infection, legume nodules do not develop visible defence reactions, suggesting a special immune status of these organs. Some factors influencing rhizobium maintenance within the plant cells have been previously identified, such as the M. truncatula NCR peptides whose toxic effects are reduced by the bacterial protein BacA. In addition, DNF2, SymCRK, and RSD are M. truncatula genes required to avoid rhizobial death within the symbiotic cells. DNF2 and SymCRK are essential to prevent defence-like reactions in nodules after bacteria internalization into the symbiotic cells. Herein, we used a combination of genetics, histology and molecular biology approaches to investigate the relationship between the factors preventing bacterial death in the nodule cells. We show that the RSD gene is also required to repress plant defences in nodules. Upon inoculation with the bacA mutant, defence responses are observed only in the dnf2 mutant and not in the symCRK and rsd mutants. In addition, our data suggest that lack of nitrogen fixation by the bacterial partner triggers bacterial death in nodule cells after bacteroid differentiation. Together our data indicate that, after internalization, at least four independent mechanisms prevent bacterial death in the plant cell. These mechanisms involve successively: DNF2, BacA, SymCRK/RSD and bacterial ability to fix nitrogen. PMID:25682610

  13. New photolithography stepping machine

    SciTech Connect

    Hale, L.; Klingmann, J.; Markle, D.

    1995-03-08

    A joint development project to design a new photolithography steeping machine capable of 150 nanometer overlay accuracy was completed by Ultratech Stepper and the Lawrence Livermore National Laboratory. The principal result of the project is a next-generation product that will strengthen the US position in step-and-repeat photolithography. The significant challenges addressed and solved in the project are the subject of this report. Design methods and new devices that have broader application to precision machine design are presented in greater detail while project specific information serves primarily as background and motivation.

  14. Stepped sinewave inverter

    NASA Astrophysics Data System (ADS)

    Appelbaum, J.; Gabbay, D.

    1984-11-01

    A stepped sinewave dc/ac inverter was analyzed for an inductive load with respect to load current and voltage, harmonics, power factor, and efficiency. This special inverter of high efficiency and low harmonic content is constructed by synthesizing the sinusoidal output by discrete voltage sources, such as storage batteries, solar cell, etc., with electronic switching of the sources at specific time intervals. The switching times are determined for the condition of minimum distortion of the synthesized wave. A 50 W inverter was built and tested to demonstrate this approach.

  15. Steps to defeat inequality.

    PubMed

    Cole, Elaine

    2016-06-15

    A team of nursing students has won a prestigious RCNi award for organising a conference aimed at reducing health inequalities affecting people with learning disabilities. The Learning Disability Awareness Network (LDAN) team was crowned winner of the RCNi Andrew Parker Student Nurse award 2016 at a ceremony held at London's Westminster Park Plaza on May 6. PMID:27305237

  16. SPAR-H Step-by-Step Guidance

    SciTech Connect

    W. J. Galyean; A. M. Whaley; D. L. Kelly; R. L. Boring

    2011-05-01

    This guide provides step-by-step guidance on the use of the SPAR-H method for quantifying Human Failure Events (HFEs). This guide is intended to be used with the worksheets provided in: 'The SPAR-H Human Reliability Analysis Method,' NUREG/CR-6883, dated August 2005. Each step in the process of producing a Human Error Probability (HEP) is discussed. These steps are: Step-1, Categorizing the HFE as Diagnosis and/or Action; Step-2, Rate the Performance Shaping Factors; Step-3, Calculate PSF-Modified HEP; Step-4, Accounting for Dependence, and; Step-5, Minimum Value Cutoff. The discussions on dependence are extensive and include an appendix that describes insights obtained from the psychology literature.

  17. Multiplication Fact Fluency Using Doubles

    ERIC Educational Resources Information Center

    Flowers, Judith M.; Rubenstein, Rheta N.

    2010-01-01

    Not knowing multiplication facts creates a gap in a student's mathematics development and undermines confidence and disposition toward further mathematical learning. Learning multiplication facts is a first step in proportional reasoning, "the capstone of elementary arithmetic and the gateway to higher mathematics" (NRC 2001, p. 242). Proportional…

  18. Estimating V0[subscript 2]max Using a Personalized Step Test

    ERIC Educational Resources Information Center

    Webb, Carrie; Vehrs, Pat R.; George, James D.; Hager, Ronald

    2014-01-01

    The purpose of this study was to develop a step test with a personalized step rate and step height to predict cardiorespiratory fitness in 80 college-aged males and females using the self-reported perceived functional ability scale and data collected during the step test. Multiple linear regression analysis yielded a model (R = 0.90, SEE = 3.43…

  19. Stair-stepped Mound

    NASA Technical Reports Server (NTRS)

    2003-01-01

    MGS MOC Release No. MOC2-429, 22 July 2003

    This April 2003 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a stair-stepped mound of sedimentary rock (right of center) on the floor of a large impact crater in western Arabia Terra near 11.0oN, 4.4oW. Sedimentary rock outcrops are common in the craters of this region. The repeated thickness and uniformity of the layers that make up this mound suggest that their depositional environment was one in which cyclic or episodic events occurred over some period of time. The sediments might have been deposited in a lake, or they may have settled directly out of the atmosphere. Most of the layered material was later eroded away, leaving this circular mound and the other nearby mesas and knobs. The image is illuminated by sunlight from the lower left.

  20. Multiple osteochondromas

    PubMed Central

    Bovée, Judith VMG

    2008-01-01

    Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection

  1. Green Schools Energy Project: A Step-by-Step Manual.

    ERIC Educational Resources Information Center

    Quigley, Gwen

    This publication contains a step-by-step guide for implementing an energy-saving project in local school districts: the installation of newer, more energy-efficient "T-8" fluorescent tube lights in place of "T-12" lights. Eleven steps are explained in detail: (1) find out what kind of lights the school district currently uses; (2) form a group to…

  2. Analysis Of Stepped Labyrinth Seals

    NASA Technical Reports Server (NTRS)

    Scharrer, Joseph K.

    1990-01-01

    Report presents analysis of compressible flow in stepped labyrinth gas seal in turbomachine. Part of continuing effort to understand and suppress self-excited vibrations caused by stepped labyrinth seals. Rotordynamic coefficients derived for compressible flow.

  3. The Stepping Stone Approach

    NASA Astrophysics Data System (ADS)

    Brumfitt, A.

    Education is a profession in its own right. It has its own parameters, passions and language. Having the responsibility both of educare and educere, education has a focus of delivering specific factual knowledge whilst drawing out the creative mind. Space Science is a special vehicle having the properties of both educare and educere. It has a magic and wonder that touches the very essence of an individual and his place in time and space; it offers the "wow" factor that all teachers strive for. Space Science is the wrapping paper for other elements in the curriculum, e.g. cross-curricula and skill-based activities, such as language development, creativity, etc. as well as the pure sciences which comprise of engineering, physics and other natural sciences from astronomy to chemistry to biology. Each of these spheres of influence are relevant from kindergarten to undergraduate studies and complement, and in addition support informal education in museums, science centers and the world of e-learning. ESA Science Education has devised the "Stepping Stone Approach" to maximize the greatest outreach to all education stakeholders in Europe. In this paper we illustrate how to best reach these target groups with very specific activities to trigger and sustain enthusiasm whilst supporting the pedagogical, subject content and skill-based needs of a prescribed curriculum.

  4. SPAR-H Step-by-Step Guidance

    SciTech Connect

    April M. Whaley; Dana L. Kelly; Ronald L. Boring; William J. Galyean

    2012-06-01

    Step-by-step guidance was developed recently at Idaho National Laboratory for the US Nuclear Regulatory Commission on the use of the Standardized Plant Analysis Risk-Human Reliability Analysis (SPAR-H) method for quantifying Human Failure Events (HFEs). This work was done to address SPAR-H user needs, specifically requests for additional guidance on the proper application of various aspects of the methodology. This paper overviews the steps of the SPAR-H analysis process and highlights some of the most important insights gained during the development of the step-by-step directions. This supplemental guidance for analysts is applicable when plant-specific information is available, and goes beyond the general guidance provided in existing SPAR-H documentation. The steps highlighted in this paper are: Step-1, Categorizing the HFE as Diagnosis and/or Action; Step-2, Rate the Performance Shaping Factors; Step-3, Calculate PSF-Modified HEP; Step-4, Accounting for Dependence, and; Step-5, Minimum Value Cutoff.

  5. Multiple Pregnancy

    MedlinePlus

    ... is called multiple pregnancy . If more than one egg is released during the menstrual cycle and each ... fraternal twins (or more). When a single fertilized egg splits, it results in multiple identical embryos. This ...

  6. Multiple myeloma

    MedlinePlus

    Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

  7. Powerlessness Reinterpreted: Reframing Step One.

    ERIC Educational Resources Information Center

    Young, Susan L.

    The 12 steps of the well-known mutual help group, Alcoholics Anonymous (AA), begin with Step One, admitting powerlessness. Although Step One has helped many problem drinkers and other addicts, its spiritual concepts have been criticized. The possibility of reconceptualizing powerlessness as empowering, not only within AA and its offshoot programs,…

  8. Finger Multiplication

    ERIC Educational Resources Information Center

    Simanihuruk, Mudin

    2011-01-01

    Multiplication facts are difficult to teach. Therefore many researchers have put a great deal of effort into finding multiplication strategies. Sherin and Fuson (2005) provided a good survey paper on the multiplication strategies research area. Kolpas (2002), Rendtorff (1908), Dabell (2001), Musser (1966) and Markarian (2009) proposed the finger…

  9. Multiple Sclerosis

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Multiple Sclerosis Information Page Condensed from Multiple Sclerosis: Hope Through ... en Español Additional resources from MedlinePlus What is Multiple Sclerosis? An unpredictable disease of the central nervous system, ...

  10. Revealing rate-limiting steps in complex disease biology: The crucial importance of studying rare, extreme-phenotype families.

    PubMed

    Chakravarti, Aravinda; Turner, Tychele N

    2016-06-01

    The major challenge in complex disease genetics is to understand the fundamental features of this complexity and why functional alterations at multiple independent genes conspire to lead to an abnormal phenotype. We hypothesize that the various genes involved are all functionally united through gene regulatory networks (GRN), and that mutant phenotypes arise from the consequent perturbation of one or more rate-limiting steps that affect the function of the entire GRN. Understanding a complex phenotype thus entails unraveling the details of each GRN, namely, the transcription factors that bind to cis regulatory elements affected by sequence variants altering transcription of specific genes, and their mutual feedback relationships. These GRNs can be identified through their rate-limiting steps and are best uncovered by genomic analyses of rare, extreme phenotype families, thus providing a coherent molecular basis to complex traits and disorders. PMID:27062178

  11. Step-step interactions on GaAs (110) nanopatterns

    SciTech Connect

    Galiana, B.; Benedicto, M.; Tejedor, P.

    2013-01-14

    The step-step interactions on vicinal GaAs (110) surface patterns have been extracted from the quantitative analysis of the terrace width distribution (TWD). We have specifically studied the interactions in near-equilibrium faceting and kinetics-driven step bunching and meandering formed by spontaneous self-organization or through the modification of GaAs growth kinetics by atomic hydrogen. We show that the experimental TWDs determined from atomic force microscopy measurements can be accurately described by a weighed sum of a generalized Wigner distribution and several Gaussians. The results of our calculations indicate that straight facets are formed during high temperature homoepitaxy due to attractive interactions between [110] steps. At low temperatures, steady state attractive interactions in [110] step bunches are preceded by a transition regime dominated by entropic and energetic repulsions between meandering [11n]-type steps (n {>=} 2), whose population density exceeds that of the [110] bunched steps. In addition, it has been found that atomic H reduces the attractive interactions between [110] bunched steps and enhances entropic and dipole-induced energetic repulsions between H-terminated [11n] steps through the inhibition of As-As bond formation at step edges. Our analysis has evidenced a correlation between the value of the adjustable parameter that accounts in our model for the specific weight of the secondary peaks in the TWD ({beta}) and the extent of transverse meandering on the vicinal surface.

  12. 15 CFR 732.2 - Steps regarding scope of the EAR.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....) Editorial Note: For Federal Register citations affecting § 732.2, see the List of CFR Sections Affected... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Steps regarding scope of the EAR. 732... FOR USING THE EAR § 732.2 Steps regarding scope of the EAR. Steps 1 though 6 are designed to aid...

  13. 15 CFR 732.2 - Steps regarding scope of the EAR.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....) Editorial Note: For Federal Register citations affecting § 732.2, see the List of CFR Sections Affected... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Steps regarding scope of the EAR. 732... FOR USING THE EAR § 732.2 Steps regarding scope of the EAR. Steps 1 though 6 are designed to aid...

  14. Multiplicity Counting

    SciTech Connect

    Geist, William H.

    2015-12-01

    This set of slides begins by giving background and a review of neutron counting; three attributes of a verification item are discussed: 240Pueff mass; α, the ratio of (α,n) neutrons to spontaneous fission neutrons; and leakage multiplication. It then takes up neutron detector systems – theory & concepts (coincidence counting, moderation, die-away time); detector systems – some important details (deadtime, corrections); introduction to multiplicity counting; multiplicity electronics and example distributions; singles, doubles, and triples from measured multiplicity distributions; and the point model: multiplicity mathematics.

  15. Multiple linear regression.

    PubMed

    Eberly, Lynn E

    2007-01-01

    This chapter describes multiple linear regression, a statistical approach used to describe the simultaneous associations of several variables with one continuous outcome. Important steps in using this approach include estimation and inference, variable selection in model building, and assessing model fit. The special cases of regression with interactions among the variables, polynomial regression, regressions with categorical (grouping) variables, and separate slopes models are also covered. Examples in microbiology are used throughout. PMID:18450050

  16. Faceting diagram for sticky steps

    NASA Astrophysics Data System (ADS)

    Akutsu, Noriko

    2016-03-01

    Faceting diagrams for the step-faceting zone, the step droplet zone, and the Gruber-Mullins-Pokrovsky-Talapov (GMPT) zone for a crystal surface are obtained by using the density matrix renormalization group method to calculate the surface tension. The model based on these calculations is the restricted solid-on-solid (RSOS) model with a point-contact-type step-step attraction (p-RSOS model) on a square lattice. The point-contact-type step-step attraction represents the energy gain obtained by forming a bonding state with orbital overlap at the meeting point of the neighboring steps. In the step-faceting zone, disconnectedness in the surface tension leads to the formation of a faceted macrostep on a vicinal surface at equilibrium. The disconnectedness in the surface tension also causes the first-order shape transition for the equilibrium shape of a crystal droplet. The lower zone boundary line (ZBL), which separates the step-faceting zone and the step droplet zone, is obtained by the condition γ 1 = lim n → ∞ γ n / n , where γn is the step tension of the n-th merged step. The upper ZBL, which separates the GMPT zone and the step droplet zone, is obtained by the condition Aq,eff = 0 and Bq,eff = 0, where Aq,eff and Bq,eff represent the coefficients for the | q → | 2 term and the | q → | 3 term, respectively, in the | q → | -expanded form of the surface free energy f eff ( q → ) . Here, q → is the surface gradient relative to the (111) surface. The reason why the vicinal surface inclined in the <101> direction does not exhibit step-faceting is explained in terms of the one-dimensional spinless quasi-impenetrable attractive bosons at absolute zero.

  17. Affective Learning.

    ERIC Educational Resources Information Center

    Brown, Charles T.

    This paper addresses itself to the question, "What does feeling have to do with knowing?" Two movements in affective education are discussed which have come into focus in recent years and which attempt to define the relationship between knowing and feeling. The first, a conscious application of the role of arousal in learning, emphasizes arousal…

  18. Step by Step to Smoke-Free Schools.

    ERIC Educational Resources Information Center

    VanSciver, James H.; Roberts, H. Earl

    1989-01-01

    This ERIC digest discusses ways of effectively banning smoking in schools so that controversies do not continue after implementation of the policy. By advocating a process approach, the document cites steps taken by the Lake Forest School Board to prohibit smoking in and around school grounds. Step one involved committee planning involving…

  19. Step-By-Step Professional Development in Technology

    ERIC Educational Resources Information Center

    Meltzer, Sarah T.

    2012-01-01

    Don't train your teachers in instructional technology without reading this resource-packed book from Sarah T. Meltzer. Meltzer presents easy-to-follow guidelines for bringing about effective professional development in technology from start to finish. She takes you step-by-step through the process of planning, implementing, and managing…

  20. Step-by-Step Visual Manuals: Design and Development

    ERIC Educational Resources Information Center

    Urata, Toshiyuki

    2004-01-01

    The types of handouts and manuals that are used in technology training vary. Some describe procedures in a narrative way without graphics; some employ step-by-step instructions with screen captures. According to Thirlway (1994), a training manual should be like a tutor that permits a student to learn at his own pace and gives him confidence for…

  1. Preface, Soil Science: A step-by-step analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book provides step-by-step procedures for soil professionals, without a lot of background theory. Chapters are targeted toward agricultural and environmental consultants, producers, students, teachers, government, and industry. Applied soil scientists gave input through a survey, which guided t...

  2. Leading Change Step-by-Step: Tactics, Tools, and Tales

    ERIC Educational Resources Information Center

    Spiro, Jody

    2010-01-01

    "Leading Change Step-by-Step" offers a comprehensive and tactical guide for change leaders. Spiro's approach has been field-tested for more than a decade and proven effective in a wide variety of public sector organizations including K-12 schools, universities, international agencies and non-profits. The book is filled with proven tactics for…

  3. Grief: Difficult Times, Simple Steps.

    ERIC Educational Resources Information Center

    Waszak, Emily Lane

    This guide presents techniques to assist others in coping with the loss of a loved one. Using the language of 9 layperson, the book contains more than 100 tips for caregivers or loved ones. A simple step is presented on each page, followed by reasons and instructions for each step. Chapters include: "What to Say"; "Helpful Things to Do"; "Dealing…

  4. Physical modeling of stepped spillways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stepped spillways applied to embankment dams are becoming popular for addressing the rehabilitation of aging watershed dams, especially those situated in the urban landscape. Stepped spillways are typically placed over the existing embankment, which provides for minimal disturbance to the original ...

  5. MULTIPLE SCALES FOR SUSTAINABLE RESULTS

    EPA Science Inventory

    This session will highlight recent research that incorporates the use of multiple scales and innovative environmental accounting to better inform decisions that affect sustainability, resilience, and vulnerability at all scales. Effective decision-making involves assessment at mu...

  6. Genetics Home Reference: multiple lentigines syndrome

    MedlinePlus

    ... often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with multiple lentigines syndrome who have heart problems have pulmonary stenosis. People with multiple lentigines ...

  7. [Affective dependency].

    PubMed

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy. PMID:23888587

  8. Affective responses to dance.

    PubMed

    Christensen, Julia F; Pollick, Frank E; Lambrechts, Anna; Gomila, Antoni

    2016-07-01

    The objective of the present work was the characterization of mechanisms by which affective experiences are elicited in observers when watching dance movements. A total of 203 dance stimuli from a normed stimuli library were used in a series of independent experiments. The following measures were obtained: (i) subjective measures of 97 dance-naïve participants' affective responses (Likert scale ratings, interviews); and (ii) objective measures of the physical parameters of the stimuli (motion energy, luminance), and of the movements represented in the stimuli (roundedness, impressiveness). Results showed that (i) participants' ratings of felt and perceived affect differed, (ii) felt and perceived valence but not arousal ratings correlated with physical parameters of the stimuli (motion energy and luminance), (iii) roundedness in posture shape was related to the experience of more positive emotion than edgy shapes (1 of 3 assessed rounded shapes showed a clear effect on positiveness ratings while a second reached trend level significance), (iv) more impressive movements resulted in more positive affective responses, (v) dance triggered affective experiences through the imagery and autobiographical memories it elicited in some people, and (vi) the physical parameters of the video stimuli correlated only weakly and negatively with the aesthetics ratings of beauty, liking and interest. The novelty of the present approach was twofold; (i) the assessment of multiple affect-inducing mechanisms, and (ii) the use of one single normed stimulus set. The results from this approach lend support to both previous and present findings. Results are discussed with regards to current literature in the field of empirical aesthetics and affective neuroscience. PMID:27235953

  9. Step-by-step growth of complex oxide microstructures

    SciTech Connect

    Datskos, Panos G.; Cullen, David A.; Sharma, Jaswinder K.

    2015-06-10

    The synthesis of complex and hybrid oxide microstructures is of fundamental interest and practical applications. However, the design and synthesis of such structures is a challenging task. We developed a solution phase process to synthesize complex silica and silica titania hybrid microstructures by exploiting the emulsion droplet based shape control and step by step growth. The strategy is robust and can be extended to make complex hybrid structures made of two or more materials while each having its own shape.

  10. The intra-rater reliability and agreement of compensatory stepping thresholds of healthy subjects.

    PubMed

    Crenshaw, Jeremy R; Kaufman, Kenton R

    2014-02-01

    The purpose of this study was to evaluate the test-retest, intra-rater reliability and agreement of compensatory stepping thresholds. A protocol was developed to establish anteroposterior single-stepping thresholds, anteroposterior multiple-stepping thresholds, and lateral single-stepping thresholds. Healthy, young subjects stood on a microprocessor-controlled treadmill, and responded to three series of progressively challenging surface translations. Subjects were instructed to "try not to step" when establishing single-stepping thresholds or "try to take only one step" when establishing multiple-stepping thresholds. Stepping thresholds were defined as the minimum disturbance magnitude that consistently elicited a single or second compensatory step. Thresholds were expressed as the ankle torque necessary to maintain upright posture. Thresholds studied included anterior single-stepping thresholds (τ = 273.0 ± 82.3 N m), posterior single-stepping, thresholds (τ = 235.5 ± 98.0 N m), anterior multiple-stepping thresholds (τ = 977.0 ± 416.3 N m), posterior multiple-stepping thresholds (τ = 701.9 ± 237.5 N m), stability-side lateral single-stepping thresholds (τ = 225.7 ± 77.7 Nm), and mobility-side lateral single-stepping thresholds (τ = 236.8 ± 85.4 N m). Based on intraclass correlation coefficients (ICC) and Bland-Altman plots, all thresholds demonstrated excellent reliability (ICC(2,1) = 0.87-0.97) and agreement. These results suggest that compensatory stepping thresholds have sufficient repeatability to be used in clinical and research-related assessments of fall-risk. Additional study is needed to determine the intra- and inter-rater reliabilities and validity of thresholds specific to the patient populations of interest. PMID:24300837

  11. Multiple myeloma

    PubMed Central

    2010-01-01

    Abstract Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management. PMID:20159661

  12. Multiple myeloma

    MedlinePlus

    Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... myeloma most commonly causes a low red blood cell count ( anemia ), which can lead to fatigue and ...

  13. Multiple myeloma.

    PubMed

    Raab, Marc S; Podar, Klaus; Breitkreutz, Iris; Richardson, Paul G; Anderson, Kenneth C

    2009-07-25

    Multiple myeloma is characterised by clonal proliferation of malignant plasma cells, and mounting evidence indicates that the bone marrow microenvironment of tumour cells has a pivotal role in myeloma pathogenesis. This knowledge has already expanded treatment options for patients with multiple myeloma. Prototypic drugs thalidomide, bortezomib, and lenalidomide have each been approved for the treatment of this disease by targeting both multiple myeloma cells and the bone marrow microenvironment. Although benefit was first shown in relapsed and refractory disease, improved overall response, duration of response, and progression-free and overall survival can be achieved when these drugs are part of first-line regimens. This treatment framework promises to improve outcome not only for patients with multiple myeloma, but also with other haematological malignancies and solid tumours. PMID:19541364

  14. Two-step electroweak baryogenesis

    NASA Astrophysics Data System (ADS)

    Inoue, Satoru; Ovanesyan, Grigory; Ramsey-Musolf, Michael J.

    2016-01-01

    We analyze electroweak baryogenesis during a two-step electroweak symmetry-breaking transition, wherein the baryon asymmetry is generated during the first step and preserved during the second. Focusing on the dynamics of C P violation required for asymmetry generation, we discuss general considerations for successful two-step baryogenesis. Using a concrete model realization, we illustrate in detail the viability of this scenario and the implications for present and future electric dipole moment (EDM) searches. We find that C P violation associated with a partially excluded sector may yield the observed baryon asymmetry while evading present and future EDM constraints.

  15. Multiple Sclerosis

    PubMed Central

    Hashimoto, S.A.; Jiwa, Theresa I.

    1991-01-01

    Successful management of patients with multiple sclerosis depends upon the involvement of the family physician. All contacts with either a multiple sclerosis clinic or a neurologist should be made at the instigation of the family practitioner. Constant contact with the family physician ensures that the individual receives proper care. While specialty care is needed for many of the symptoms, psychosocial problems are dealt with best by the individual's own family physician. PMID:21229090

  16. Multiple pterygium syndrome.

    PubMed

    Chen, H; Chang, C H; Misra, R P; Peters, H A; Grijalva, N S; Opitz, J M

    1980-01-01

    We describe a sporadic case and four sibs from a consanguineous Nicaraguan family affected with the multiple pterygium syndrome. Clinical manifestations included normal intelligence; short stature; pterygia of neck, axillary, antecubital, popliteal, digital, and intercrural areas; multiple joint contractures with a crouched stance; a flat, sad, motionless facial appearance; and cleft palate. Males had small penis and scrotum and cryptorchidism; females had apparent aplasia of labia majora and small clitoris. Skeletal anomalies included fusion of cervical vertebrae, scoliosis, flexion contractures of fingers and "rocker-bottom" feet with vertical talus. This review documents genetic heterogeneity: Autosomal recessive inheritance in many cases, autosomal dominant determination in others, and sporadic occurrence. PMID:7468651

  17. CDC Vital Signs: Hospital Actions Affect Breastfeeding

    MedlinePlus

    ... Read the MMWR Science Clips Hospital Actions Affect Breastfeeding Language: English Español (Spanish) Recommend on Facebook Tweet ... in many US hospitals do not fully support breastfeeding. Some of the Ten Steps on which hospitals ...

  18. 7 Steps to Aging Well

    MedlinePlus

    ... Issue Past Issues Special Section 7 Steps to Aging Well Past Issues / Winter 2007 Table of Contents ... Exercise: A Guide from the National Institute on Aging is a publication from NIA that has strength, ...

  19. Atomic friction at exposed and buried graphite step edges: Experiments and simulations

    SciTech Connect

    Ye, Zhijiang; Martini, Ashlie

    2015-06-08

    The surfaces of layered materials such as graphite exhibit step edges that affect friction. Step edges can be exposed, where the step occurs at the outmost layer, or buried, where the step is underneath another layer of material. Here, we study friction at exposed and buried step edges on graphite using an atomic force microscope (AFM) and complementary molecular dynamics simulations of the AFM tip apex. Exposed and buried steps exhibit distinct friction behavior, and the friction on either step is affected by the direction of sliding, i.e., moving up or down the step, and the bluntness of the tip. These trends are analyzing in terms of the trajectory of the AFM tip as it moves over the step, which is a convolution of the topography of the surface and the tip shape.

  20. [Multiple meningiomas].

    PubMed

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. PMID:27234913

  1. Stutter-Step Models of Performance in School

    ERIC Educational Resources Information Center

    Morgan, Stephen L.; Leenman, Theodore S.; Todd, Jennifer J.; Kentucky; Weeden, Kim A.

    2013-01-01

    To evaluate a stutter-step model of academic performance in high school, this article adopts a unique measure of the beliefs of 12,591 high school sophomores from the Education Longitudinal Study, 2002-2006. Verbatim responses to questions on occupational plans are coded to capture specific job titles, the listing of multiple jobs, and the listing…

  2. The USMLE Step 2 CS: Time for a change.

    PubMed

    Alvin, Matthew D

    2016-08-01

    The United States Medical Licensing Examination (USMLE(®)) Steps are a series of mandatory licensing assessments for all allopathic (MD degree) medical students in their transition from student to intern to resident physician. Steps 1, 2 Clinical Knowledge (CK), and 3 are daylong multiple-choice exams that quantify a medical student's basic science and clinical knowledge as well as their application of that knowledge using a three-digit score. In doing so, these Steps provide a standardized assessment that residency programs use to differentiate applicants and evaluate their competitiveness. Step 2 Clinical Skills (CS), the only other Step exam and the second component of Step 2, was created in 2004 to test clinical reasoning and patient-centered skills. As a Pass/Fail exam without a numerical scoring component, Step 2 CS provides minimal differentiation among applicants for residency programs. In this personal view article, it is argued that the current Step 2 CS exam should be eliminated for US medical students and propose an alternative consistent with the mission and purpose of the exam that imposes less of a burden on medical students. PMID:27007882

  3. Step-by-Step Growth of Complex Oxide Microstructures.

    PubMed

    Datskos, Panos; Cullen, David A; Sharma, Jaswinder

    2015-07-27

    The synthesis of complex and hybrid oxide microstructures is of fundamental interest and practical applications. However, the design and synthesis of such structures is a challenging task. A solution-phase process to synthesize complex silica and silica-titania hybrid microstructures was developed by exploiting the emulsion-droplet-based step-by-step growth featuring shape control. The strategy is robust and can be extended to the preparation of complex hybrid structures consisting of two or more materials, with each having its own shape. PMID:26095228

  4. A step-by-step methodology for enterprise interoperability projects

    NASA Astrophysics Data System (ADS)

    Chalmeta, Ricardo; Pazos, Verónica

    2015-05-01

    Enterprise interoperability is one of the key factors for enhancing enterprise competitiveness. Achieving enterprise interoperability is an extremely complex process which involves different technological, human and organisational elements. In this paper we present a framework to help enterprise interoperability. The framework has been developed taking into account the three domains of interoperability: Enterprise Modelling, Architecture and Platform and Ontologies. The main novelty of the framework in comparison to existing ones is that it includes a step-by-step methodology that explains how to carry out an enterprise interoperability project taking into account different interoperability views, like business, process, human resources, technology, knowledge and semantics.

  5. Writing a Simulation Scenario: A Step-By-Step Guide.

    PubMed

    Bambini, Deborah

    2016-02-01

    Simulation is becoming a widely used method of helping nurses learn and maintain competency in the clinical area for both staff educators in clinical settings and nursing faculty in academic settings. Designing an effective simulation experience requires thoughtful planning, knowledge of educational principles, and knowledge of best practices in both simulation and clinical practice. An evidence-based strategy for writing a simulation scenario for nurses and other health care providers in any setting is described. A step-by-step process is outlined that incorporates best practices. Examples and suggestions are provided to help readers create quality simulation experiences. PMID:26909455

  6. Partial Return Yoke for MICE Step IV and Final Step

    SciTech Connect

    Witte, Holger; Plate, Stephen; Berg, J.Scott; Tarrant, Jason; Bross, Alan

    2015-06-01

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  7. Partial return yoke for MICE step IV and final step

    SciTech Connect

    Witte, H.; Plate, S.; Berg, J. S.; Tarrant, J.; Bross, A.

    2015-05-03

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  8. One step beyond: Different step-to-step transitions exist during continuous contact brachiation in siamangs

    PubMed Central

    Michilsens, Fana; D'Août, Kristiaan; Vereecke, Evie E.; Aerts, Peter

    2012-01-01

    Summary In brachiation, two main gaits are distinguished, ricochetal brachiation and continuous contact brachiation. During ricochetal brachiation, a flight phase exists and the body centre of mass (bCOM) describes a parabolic trajectory. For continuous contact brachiation, where at least one hand is always in contact with the substrate, we showed in an earlier paper that four step-to-step transition types occur. We referred to these as a ‘point’, a ‘loop’, a ‘backward pendulum’ and a ‘parabolic’ transition. Only the first two transition types have previously been mentioned in the existing literature on gibbon brachiation. In the current study, we used three-dimensional video and force analysis to describe and characterize these four step-to-step transition types. Results show that, although individual preference occurs, the brachiation strides characterized by each transition type are mainly associated with speed. Yet, these four transitions seem to form a continuum rather than four distinct types. Energy recovery and collision fraction are used as estimators of mechanical efficiency of brachiation and, remarkably, these parameters do not differ between strides with different transition types. All strides show high energy recoveries (mean  = 70±11.4%) and low collision fractions (mean  = 0.2±0.13), regardless of the step-to-step transition type used. We conclude that siamangs have efficient means of modifying locomotor speed during continuous contact brachiation by choosing particular step-to-step transition types, which all minimize collision fraction and enhance energy recovery. PMID:23213432

  9. Familial multiple lipomatosis.

    PubMed

    Rabbiosi, G; Borroni, G; Scuderi, N

    1977-01-01

    A clinical study was made of 14 cases of multiple symmetrical lipomata in two families. There were 7 female and 7 male patients. In one family the members affected were observed in four generations. The disease set in during the third or fourth decade of life. The lipomata ranged in size from that of a pea to that of a hen's egg. They were limited to the forearms and trunk were asymptomatic. PMID:71835

  10. Pregnancy and multiple sclerosis

    PubMed Central

    Airas, Laura; Kaaja, Risto

    2012-01-01

    The relapse rate of multiple sclerosis (MS) is typically reduced during late pregnancy but increases in the postpartum period. The reasons for the increased postpartum activity are not entirely clear, but factors such as the abrupt decrease in oestrogen levels immediately after the delivery and the loss of the immunosuppressive state of pregnancy are likely of importance. There is a general view that MS does not affect the course or outcome of pregnancy.

  11. KEEPING A STEP AHEAD - FORMATIVE PHASE OF A WORKPLACE INTERVENTION TRIAL TO PREVENT OBESITY

    PubMed Central

    Zapka, Jane; Lemon, Stephenie C.; Estabrook, Barbara B.; Jolicoeur, Denise G.

    2008-01-01

    Background Ecological interventions hold promise for promoting overweight and obesity prevention in worksites. Given the paucity of evaluative research in the hospital worksite setting, considerable formative work is required for successful implementation and evaluation. Purpose This paper describes the formative phases of Step Ahead, a site-randomized controlled trial of a multi-level intervention that promotes physical activity and healthy eating in 6 hospitals in central Massachusetts. The purpose of the formative research phase was to increase the feasibility, effectiveness and likelihood of sustainability of the intervention. Design and Procedures The Step Ahead ecological intervention approach targets change at the organization, the interpersonal work environment and the individual levels. The intervention was developed using fundamental steps of intervention mapping and important tenets of participatory research. Formative research methods were used to engage leadership support and assistance and to develop an intervention plan that is both theoretically and practically grounded. This report uses observational data, program minutes and reports, and process tracking data. Developmental Strategies and Observations Leadership involvement (key informant interviews and advisory boards), employee focus groups and advisory boards, and quantitative environmental assessments cultivated participation and support. Determining multiple foci of change and designing measurable objectives and generic assessment tools to document progress are complex challenges encountered in planning phases. Lessons Learned Multi-level trials in diverse organizations require flexibility and balance of theory application and practice-based perspectives to affect impact and outcome objectives. Formative research is an essential component. PMID:18073339

  12. Multiple sclerosis

    MedlinePlus

    ... incontinence ) Eye symptoms: Double vision Eye discomfort Uncontrollable eye movements Vision loss (usually affects one eye at a ... pupil responses Changes in the visual fields or eye movements Decreased visual acuity Problems with the inside parts ...

  13. Longitudinal Changes in Self-Reported Walking Ability in Multiple Sclerosis

    PubMed Central

    Motl, Robert W.; Putzki, Norman; Pilutti, Lara A.; Cadavid, Diego

    2015-01-01

    Background Patient-reported outcomes are increasingly used to understand the clinical meaningfulness of multiple sclerosis disability and its treatments. For example, the 12-item Multiple Sclerosis Walking Scale (MSWS-12) measures the patient-reported impact of the disease on walking ability. Objective We studied longitudinal changes in walking ability using the MSWS-12 in a cohort of 108 patients with relapsing-remitting multiple sclerosis and moderate-to-severe disability from a single US center cohort study investigating multiple sclerosis symptoms and physical activity. Methods The MSWS-12 was completed every 6 months over 2 years together with self-reported measures of disease impact on daily life (Multiple Sclerosis Impact Scale) and walking disability (Patient Determined Disease Steps scale). Results The results revealed a high frequency of self-reported changes in walking ability at the individual level, affecting approximately 80% of patients for all four time periods. MSWS-12 scores remained stable at the group level for all four time periods. The magnitude of observed changes at the individual level was higher than the proposed minimal clinically important differences of 4 or 6 points and correlated better with Multiple Sclerosis Impact Scale physical scores than psychological scores, but little with self-reported Patient Determined Disease Steps Scale scores. Conclusions This novel finding of frequent fluctuations in self-reported walking ability is new and requires further investigation. PMID:25932911

  14. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  15. Finger Multiplication

    ERIC Educational Resources Information Center

    Holmes, Bill

    2010-01-01

    The author has been prompted to write this article about finger multiplication for a number of reasons. Firstly there are a number of related articles in past issues of "Mathematics Teaching" ("MT") which have connections to this algorithm. Secondly, very few of his primary teaching students and professional colleagues appear to be aware of the…

  16. A Step-by-Step Guide to Personalize Learning

    ERIC Educational Resources Information Center

    Bray, Barbara; McClaskey, Kathleen

    2013-01-01

    It is known that every learner is unique and that one-size-fits-all instruction does not work for most. How can a classroom environment be created that gives each learner voice and choice? The co-founders of Personalize Learning, LLC, offer a detailed six-step approach. This article provides the background on what is and what is not Personalized…

  17. Step fluctuations and step interactions on Mo(0 1 1)

    NASA Astrophysics Data System (ADS)

    Ondrejcek, M.; Swiech, W.; Durfee, C. S.; Flynn, C. P.

    2003-09-01

    Step fluctuations have been studied on Mo(0 1 1) thin single crystal films with various orientations of miscut, in order to determine the step stiffnesses. Effects of unseen defect structures were clearly visible in some data. Measurements of fluctuation amplitudes and relaxation times were made in the temperature range 1100-1680 K. The results show an anisotropic stiffness of about 0.36 eV/nm along [0 1¯ 1] and about 0.15 eV/nm along [1 0 0]. No temperature dependence of the stiffness was detected. The step free energies derived from the stiffnesses average about 0.27 eV/nm and are less anisotropic by about a factor 3. From the temperature dependence of the relaxation rates, an activation energy of 0.8 ± 0.2 eV was determined for the mass diffusion of the mobile defects responsible for the fluctuations. An appendix details an investigation of correlations induced in the motions of neighboring steps by diffusion and by energetic interactions.

  18. Step by Step to Your New Camp Brochure.

    ERIC Educational Resources Information Center

    Cole, Bill

    1993-01-01

    Describes steps in developing camp brochures: examining brochures of competing camps; deciding on a message; hiring professional designers and photographers; writing the copy; determining marketing strategies and quantity of brochures needed; reviewing final photo choices; evaluating the brochure; and planning for brochure mailings. (LP)

  19. Writing the Winning Dissertation: A Step-By-Step Guide.

    ERIC Educational Resources Information Center

    Glatthorn, Allan A.

    This book is a practical guide to researching and writing the doctoral dissertation or master's thesis. Part 1 offers seven chapters on preparatory steps: laying the groundwork for the thesis and dissertation; finding a research problem; conducting a focused review of the literature; making a preliminary choice of methodology; organizing and…

  20. Publishing Ethical Research: A Step-by-Step Overview

    ERIC Educational Resources Information Center

    Wester, Kelly L.

    2011-01-01

    To publish ethical research, one must conduct research responsibly, making ethical choices from the inception of the research idea and throughout the research process. Conducting and publishing ethical research is important because of the impact the results will have on the counseling profession. Steps to consider are discussed.

  1. Cataloging Books Step by Step. CSLA Guide No. 5.

    ERIC Educational Resources Information Center

    Smith, Ruth S.

    Designed as a beginning, how-to guide, this handbook lists 20 short steps to cataloging library materials for a church or synagogue library. The guide opens with a history and a brief explanation of the Dewey Decimal System, with special attention given to the divisions and subdivisions that fall under the category "Religion." Several references…

  2. 15 CFR 732.2 - Steps regarding scope of the EAR.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... section. (2) Editorial Note: For Federal Register citations affecting § 732.2, see the List of CFR... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Steps regarding scope of the EAR. 732... FOR USING THE EAR § 732.2 Steps regarding scope of the EAR. Steps 1 though 6 are designed to aid...

  3. Piezoelectric step-motion actuator

    DOEpatents

    Mentesana; Charles P.

    2006-10-10

    A step-motion actuator using piezoelectric material to launch a flight mass which, in turn, actuates a drive pawl to progressively engage and drive a toothed wheel or rod to accomplish stepped motion. Thus, the piezoelectric material converts electrical energy into kinetic energy of the mass, and the drive pawl and toothed wheel or rod convert the kinetic energy of the mass into the desired rotary or linear stepped motion. A compression frame may be secured about the piezoelectric element and adapted to pre-compress the piezoelectric material so as to reduce tensile loads thereon. A return spring may be used to return the mass to its resting position against the compression frame or piezoelectric material following launch. Alternative embodiment are possible, including an alternative first embodiment wherein two masses are launched in substantially different directions, and an alternative second embodiment wherein the mass is eliminated in favor of the piezoelectric material launching itself.

  4. Steps of Reprocessing and Equipments

    PubMed Central

    Lee, Yong Kook

    2013-01-01

    With the increasing interest in endoscopy and the rising number of endoscopic examinations in hospitals, the importance of endoscopic reprocessing is also increasing. Cure facilities that are understaffed and ill-equipped are trying to cope with the problems of insufficient cleaning and high infection risks. To prevent endoscopy-associated infection, the endoscope cleaning, and disinfection guidelines prepared by the Korean Society of Gastrointestinal Endoscopy must be followed. In this review, the steps of endoscopic reprocessing and the equipments required in each step are discussed. PMID:23767039

  5. Experimental study on cyclic steps formed by surge-type turbidity currents

    NASA Astrophysics Data System (ADS)

    Yokokawa, M.; Shozakai, D.; Higuchi, H.; Hughes Clarke, J. E.; Izumi, N.

    2015-12-01

    Field observations of turbidity currents and seabed topography on the Squamish delta in Howe Sound, British Columbia, Canada have been undertaken which found bedwaves actively migrating in the upstream direction in channels formed on the prodelta slope (Hughes Clarke et al., 2012a; 2012b; 2014; Figure 1). Their topography and behaviour suggest that they are cyclic steps formed by the surge-type turbidity currents. There has been no experimental study to investigate the formative conditions of cyclic steps by the surge-type turbidity currents. We did preliminary experiments on the formation of cyclic steps due to the multiple surge-type density currents, and compare the morphology of the steps with those of Squamish delta. The experiments had been performed at Osaka Institute of Technology. A flume, which is 3.6 m long, 0.3 m deep and 2 cm wide, was submerged into a larger flume, which is 4 m long, 0.4 m deep and 8 cm wide, filled with water. Mixture of salt water (1.18 g/cm3) and plastic particles (1.5 g/cm3, 0.1-0.18 mm in diameter) poured into the upstream end of the inner flume by hand using a funnel. For the example introduced here, the slope of the outer flume was 1.5 degrees, and the mixtures' whole weight and volumetric concentration ranged from 310 g (3.23 vol.%) to 510 g (8.16 vol.%). These mixtures were poured 105 times, and the thickness of the deposits was measured every 50 cm by photographs. As a result, two mounds (steps) were formed ultimately, which are moving toward upstream direction. Wavelengths are 80 cm and 120 cm respectively. The two kinds of flow depth were measured from photograph, such as the whole thickness of the flow, and the thickness of the lower high-density layer. Calculating the wave steepness and non-dimensional wave number, it turns out that those values using the thickness of the lower high-density layer fall into the region very close to the Squamish data that assuming the flow depth as 0.5 m. This could lead the following

  6. Impact of previous one-step variation in positively long-range correlated processes

    NASA Astrophysics Data System (ADS)

    Fu, Zuntao; Xie, Fenghua; Yuan, Naiming; Piao, Lin

    2016-04-01

    In a positively long-range correlated process, variations among consecutive steps are interdependent, especially the influence of previous one-step variation on next steps. How to quantify this kind of impact is of great importance to predict the future variations. In this paper, we demonstrate that this kind of impact depends on the memory strength of underlying processes from two aspects based on the theoretical and observational calculations. More precisely, the conditional calculations and the marginal distribution of the next step variation with given distribution of the previous one-step variation. Both the theoretical and observational calculations demonstrate that the previous one-step variation affect greatly the variation for the next one-step, and the expectation of next step variation will shift to larger value as the increase of memory strength but with a much smaller uncertainty. This is beneficial for our one-step ahead prediction, and will be especially beneficial for multi-step ahead prediction.

  7. Evaluation of the Randomized Multiple Choice Format.

    ERIC Educational Resources Information Center

    Harke, Douglas James

    Each physics problem used in evaluating the effectiveness of Randomized Multiple Choice (RMC) tests was stated in the conventional manner and was followed by several multiple choice items corresponding to the steps in a written solution but presented in random order. Students were instructed to prepare a written answer and to use it to answer the…

  8. Illinois, An Educational Step Backward.

    ERIC Educational Resources Information Center

    Jones, Scott

    Conclusions reached by the Illinois State Board of Education Study, released in May 1985, that small schools are inferior and inefficient, that Illinois has too many schools, and that over half its schools should be closed seem to be an educational step backward. Without linking the two concepts, the study implies that school consolidation will…

  9. 10 Steps for Implementing Change.

    ERIC Educational Resources Information Center

    Marsee, Jeff

    2002-01-01

    Offers steps for adapting the change process to institutional culture: align leadership style with organizational culture, don't overuse change missionaries, protect change agents, define the problem, maintain focus when the project drifts, identify and remove barriers before implementing action plans, assign responsibilities to individuals,…

  10. One-Step Coal Liquefaction

    NASA Technical Reports Server (NTRS)

    Qader, S. A.

    1984-01-01

    Steam injection improves yield and quality of product. Single step process for liquefying coal increases liquid yield and reduces hydrogen consumption. Principal difference between this and earlier processes includes injection of steam into reactor. Steam lowers viscosity of liquid product, so further upgrading unnecessary.

  11. Design of converging stepped spillways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Roller compacted concrete (RCC) stepped spillways are growing in popularity for providing overtopping protection for aging watershed dams with inadequate auxiliary spillway capacity and for the construction of new dams. Unobtainable land rights, topographic features, and land use changes caused by ...

  12. Seven Steps to Successful Inclusion.

    ERIC Educational Resources Information Center

    Whitworth, Jerry

    This report highlights the experiences of the Lighthouse Project, which successfully included students with disabilities in elementary, middle, and high school general education classes in a school district in southwest Tennessee. Drawing on findings from the Lighthouse Project, the report describes the following seven steps that must be present…

  13. Evaluation of Florida's STEP Program.

    ERIC Educational Resources Information Center

    Florida State Dept. of Health and Rehabilitative Services, Tallahassee.

    Project STEP (Short Term Elective Program) is an outdoor-educational program that, through teaching wilderness survival skills and affording a necessity for their use, provides juvenile delinquents with a feeling of self-reliance and self-worth. The program is designed for committed youths, primarily males, at least 13 to 14 years of age, but…

  14. Initial steps of aerosol growth

    NASA Astrophysics Data System (ADS)

    Kulmala, M.; Laakso, L.; Lehtinen, K. E. J.; Riipinen, I.; Dal Maso, M.; Anttila, T.; Kerminen, V.-M.; Hõrrak, U.; Vana, M.; Tammet, H.

    2004-12-01

    The formation and growth of atmospheric aerosols depend on several steps, namely nucleation, initial steps of growth and subsequent - mainly condensational - growth. This work focuses on the initial steps of growth, meaning the growth right after nucleation, where the interplay of curvature effects and thermodynamics has a significant role on the growth kinetics. More specifically, we investigate how ion clusters and aerosol particles grow from 1.5 nm to 20 nm (diameter) in atmospheric conditions using experimental data obtained by air ion and aerosol spectrometers. The measurements have been performed at a boreal forest site in Finland. The observed trend that the growth rate seems to increase as a function of size can be used to investigate possible growth mechanisms. Such a growth rate is consistent with a recently suggested nano-Köhler mechanism, in which growth is activated at a certain size with respect to condensation of organic vapors. The results also imply that charge-enhanced growth associated with ion-mediated nucleation plays only a minor role in the initial steps of growth, since it would imply a clear decrease of the growth rate with size. Finally, further evidence was obtained on the earlier suggestion that atmospheric nucleation and the subsequent growth of fresh nuclei are likely to be uncoupled phenomena via different participating vapors.

  15. Initial steps of aerosol growth

    NASA Astrophysics Data System (ADS)

    Kulmala, O.; Laakso, L.; Lehtinen, K. E. J.; Riipinen, I.; Dal Maso, M.; Anttila, T.; Kerminen, V.-M.; Hõrrak, U.; Vana, M.; Tammet, H.

    2004-09-01

    The formation and growth of atmospheric aerosols depend on several steps, namely nucleation, initial steps of growth and subsequent - mainly condensational - growth. This work focuses on the initial steps of growth, meaning the growth right after nucleation, where the interplay of curvature effects and thermodynamics has a significant role on the growth kinetics. More specifically, we investigate how ion clusters and aerosol particles grow from 1.5 nm to 20 nm in atmospheric conditions using experimental data obtained by air ion and aerosol spectrometers. The measurements have been performed at a boreal forest site in Finland. The observed trend that the growth rate seems to increase as a function of size can be used to investigate possible growth mechanisms. Such a growth rate is consistent with a recently suggested nano-Köhler mechanism, in which growth is activated at a certain size with respect to condensation of organic vapors. The results also imply that charge-enhance growth associated with ion-mediated nucleation plays only a minor role in the initial steps of growth, since it would imply a clear decrease of the growth rate with size. Finally, further evidence was obtained on the earlier suggestion that atmospheric nucleation and the subsequent growth of fresh nuclei are likely to be uncoupled phenomena via different participating vapors.

  16. Altered molecular expression of TLR-signaling pathways affects the steady-state release of IL-12p70 and IFN-α in patients with relapsing-remitting multiple sclerosis.

    PubMed

    Deckx, Nathalie; Willekens, Barbara; Wens, Inez; Eijnde, Bert O; Goossens, Herman; Van Damme, Pierre; Berneman, Zwi N; Cools, Nathalie

    2016-05-01

    Recent evidence suggests a key role of dendritic cells (DC) in the immunopathogenesis of multiple sclerosis (MS). Whereas dysfunction of DC was reported in MS patients, the underlying cause for this is not fully elucidated yet. The aim of the present study was to compare the gene expression profile of molecules involved in TLR4 and TLR7 signaling in DC from patients with MS and healthy controls. For this, circulating DC subsets were purified from patients with relapsing-remitting MS (RRMS) and from healthy controls for quantitative real-time PCR analysis. Additionally, TLR responsiveness in peripheral blood was investigated. We observed an aberrant steady-state release of IL-12p70 and IFN-α in patients with RRMS compared with healthy controls. Expression of IRF1 and JUN was reduced in conventional DC from patients with RRMS. In plasmacytoid DC from patients with RRMS, expression of IRF7 and IFNGR1 was reduced, while higher expression levels of TLR4 and LY86 were found compared with DC from healthy controls. The observed alterations in the gene expression of molecules involved in the TLR4 and TLR7 signaling pathways in circulating DC subsets may underlie the impaired IL-12p70 and IFN-α secretion in patients with RRMS, thereby potentially contributing to the disease pathogenesis of MS. PMID:27036414

  17. Footprint reduction's 'multiple paybacks'.

    PubMed

    2010-06-01

    Some of the measures that EFM personnel can take to further reduce their estates' carbon footprint at a time when pressure to cut energy consumption must be balanced both against the requirement to create the best possible patient environment, and new medical technology that may require substantial energy to operate, were the focus of a recent IHEEM carbon reduction seminar in London. The one-day event, "Planning to achieve Carbon Reduction Commitment targets for healthcare premises", also included a look at the key steps affected healthcare organisations, and especially their estates teams, need to be taking already to ensure compliance with the new Carbon Reduction Commitment scheme. PMID:20597381

  18. Harmonic Ratios: A quantification of step to step symmetry

    PubMed Central

    Roche, J.L; Lowry, K.A; Vanswearingen, J.M; Brach, J.S; Redfern, M.S

    2013-01-01

    The harmonic ratio (HR), derived from Fourier analysis of trunk accelerations, has been described in various ways as a measure of walking smoothness, walking rhythmicity, or dynamic stability. There is increasing interest in applying the HR technique to investigate the impact of various pathologies on locomotion; however, explanation of the method has been limited. The aim hereis to present a clear description of the mathematical basis of HRs and an understanding of their interpretation. We present harmonic theory, the interpretation of the HR using sinusoidal signals, and an exampleusing actual trunk accelerations and harmonic analyses during limb-loading conditions. We suggest that the HR method may be better defined, not as a measure of rhythmicity or stability, but as a measure of step-to-step symmetry within a stride. PMID:23317758

  19. 2-Step IMAT and 2-Step IMRT in three dimensions

    SciTech Connect

    Bratengeier, Klaus

    2005-12-15

    In two dimensions, 2-Step Intensity Modulated Arc Therapy (2-Step IMAT) and 2-Step Intensity Modulated Radiation Therapy (IMRT) were shown to be powerful methods for the optimization of plans with organs at risk (OAR) (partially) surrounded by a target volume (PTV). In three dimensions, some additional boundary conditions have to be considered to establish 2-Step IMAT as an optimization method. A further aim was to create rules for ad hoc adaptations of an IMRT plan to a daily changing PTV-OAR constellation. As a test model, a cylindrically symmetric PTV-OAR combination was used. The centrally placed OAR can adapt arbitrary diameters with different gap widths toward the PTV. Along the rotation axis the OAR diameter can vary, the OAR can even vanish at some axis positions, leaving a circular PTV. The width and weight of the second segment were the free parameters to optimize. The objective function f to minimize was the root of the integral of the squared difference of the dose in the target volume and a reference dose. For the problem, two local minima exist. Therefore, as a secondary criteria, the magnitude of hot and cold spots were taken into account. As a result, the solution with a larger segment width was recommended. From plane to plane for varying radii of PTV and OAR and for different gaps between them, different sets of weights and widths were optimal. Because only one weight for one segment shall be used for all planes (respectively leaf pairs), a strategy for complex three-dimensional (3-D) cases was established to choose a global weight. In a second step, a suitable segment width was chosen, minimizing f for this global weight. The concept was demonstrated in a planning study for a cylindrically symmetric example with a large range of different radii of an OAR along the patient axis. The method is discussed for some classes of tumor/organ at risk combinations. Noncylindrically symmetric cases were treated exemplarily. The product of width and weight of

  20. Time of interferon-beta 1a injection and duration of treatment affect clinical side effects and acute changes of plasma hormone and cytokine levels in multiple sclerosis patients.

    PubMed

    Kümpfel, T; Schwan, M; Pollmächer, Th; Yassouridis, A; Uhr, M; Trenkwalder, C; Weber, F

    2007-11-01

    During initiation of interferon-beta (IFN-beta) therapy, many multiple sclerosis (MS) patients experience systemic side effects which may depend on the time point of IFN-beta injection. We investigated the time course of plasma hormone-, cytokine- and cytokine-receptor concentrations after the first injection of IFN-beta either at 8.00 a.m. (group A) or at 6.00 p.m. (group B) and quantified clinical side effects within the first 9 h in 16 medication free patients with relapsing-remitting MS. This investigation was repeated after 6-month IFN-beta therapy. Plasma ACTH and cortisol concentrations followed their physiological rhythms, with lower levels in the evening compared to the morning, but raised earlier and stronger in group B after IFN-beta administration. IFN-beta injection in the evening led to a prompter increase of plasma IL-6 concentrations and temperature during the first hours and correlated to more intense clinical side effects compared to group A. Plasma IL-10 concentrations increased more in group A compared to group B, but sTNF-RI and sTNF-RII concentrations raised 7 h after IFN-beta injection only in group B. Acute effects on plasma hormone and cytokine concentrations adapted after 6-month IFN-beta treatment, while diurnal variations were still present. Baseline sTNF-RII concentrations were elevated after 6-month IFN-beta therapy only in group A. Our results show that time point of IFN-beta injection has differential effects on acute changes of plasma hormone and cytokine concentrations and is related to systemic side effects. This may have implications on the tolerability and effectiveness of IFN-beta therapy. PMID:17967841

  1. Stepping Out: An Overview of the STEP Curriculum. Secondary Transition and Employment Project: STEP.

    ERIC Educational Resources Information Center

    Baumgart, Diane; Anderson, Jane

    The guide, developed by the Secondary Transition and Employment Project (STEP) in Idaho, provides an overview of its sequential vocational curriculum intended to help students with mild, moderate, and severe handicaps to: (1) identify their vocational preferences and aptitudes; (2) use community resources to find out about jobs; (3) observe and…

  2. A step-by-step procedure for pH model construction in aquatic systems

    NASA Astrophysics Data System (ADS)

    Hofmann, A. F.; Meysman, F. J. R.; Soetaert, K.; Middelburg, J. J.

    2007-10-01

    We present, by means of a simple example, a comprehensive step-by-step procedure to consistently derive a pH model of aquatic systems. As pH modeling is inherently complex, we make every step of the model generation process explicit, thus ensuring conceptual, mathematical, and chemical correctness. Summed quantities, such as total inorganic carbon and total alkalinity, and the influences of modeled processes on them are consistently derived. The model is subsequently reformulated until numerically and computationally simple dynamical solutions, like a variation of the operator splitting approach (OSA) and the direct substitution approach (DSA), are obtained. As several solution methods are pointed out, connections between previous pH modelling approaches are established. The final reformulation of the system according to the DSA allows for quantification of the influences of kinetic processes on the rate of change of proton concentration in models containing multiple biogeochemical processes. These influences are calculated including the effect of re-equilibration of the system due to a set of acid-base reactions in local equilibrium. This possibility of quantifying influences of modeled processes on the pH makes the end-product of the described model generation procedure a powerful tool for understanding the internal pH dynamics of aquatic systems.

  3. Meeting the Needs of Children with the 5-Step Method

    ERIC Educational Resources Information Center

    Templeton, Lorna

    2010-01-01

    The stress-strain-coping-support model of how adult family members are affected by a relative's substance misuse is equally relevant to children who live with parental or familial substance misuse. To date, the main beneficiaries of the 5-Step Method have been adult family members, yet children can benefit from familial intervention generally and…

  4. Multiple myeloma

    PubMed Central

    Rajkumar, S. Vincent

    2008-01-01

    Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. In this paper, we present a historically focused review of the disease, from the description of the first case in 1844 to the present. The evolution of drug therapy and stem-cell transplantation for the treatment of myeloma, as well as the development of new agents, is discussed. We also provide an update on current concepts of diagnosis and therapy, with an emphasis on how treatments have emerged from a historical perspective after certain important discoveries and the results of experimental studies. PMID:18332230

  5. Segmented Coil Fails In Steps

    NASA Technical Reports Server (NTRS)

    Stedman, Ronald S.

    1990-01-01

    Electromagnetic coil degrades in steps when faults occur, continues to operate at reduced level instead of failing catastrophically. Made in segments connected in series and separated by electrically insulating barriers. Fault does not damage adjacent components or create hazard. Used to control valves in such critical applications as cooling systems of power generators and chemical process equipment, where flammable liquids or gases handled. Also adapts to electrical control of motors.

  6. Meissner-Effect Stepping Motor

    NASA Technical Reports Server (NTRS)

    Robertson, Glen A.

    1991-01-01

    Proposed stepping motor derives torque from diamagnetic repulsion produced by Meissner effect - exclusion of magnetic field from interior of superconductor. Design of motor takes advantage of silver-doped YB2Cu3O and other compounds superconductive at temperatures as high as that of liquid nitrogen. Skin of rotor cooled below its superconducting-transition temperature by liquid nitrogen. O-rings prevent leaks of liquid nitrogen from rotor. Weight, cost, and maintenance reduced.

  7. Stepped frequency ground penetrating radar

    DOEpatents

    Vadnais, Kenneth G.; Bashforth, Michael B.; Lewallen, Tricia S.; Nammath, Sharyn R.

    1994-01-01

    A stepped frequency ground penetrating radar system is described comprising an RF signal generating section capable of producing stepped frequency signals in spaced and equal increments of time and frequency over a preselected bandwidth which serves as a common RF signal source for both a transmit portion and a receive portion of the system. In the transmit portion of the system the signal is processed into in-phase and quadrature signals which are then amplified and then transmitted toward a target. The reflected signals from the target are then received by a receive antenna and mixed with a reference signal from the common RF signal source in a mixer whose output is then fed through a low pass filter. The DC output, after amplification and demodulation, is digitized and converted into a frequency domain signal by a Fast Fourier Transform. A plot of the frequency domain signals from all of the stepped frequencies broadcast toward and received from the target yields information concerning the range (distance) and cross section (size) of the target.

  8. Decision making. A step-by-step process.

    PubMed

    McConnell, E A

    1989-05-01

    Some decisions affect no one but ourselves, and others affect more than one person. Some decisions are quite simple and have minimal, if any, ramifications; other decisions are more complex and can have major ramifications. Some decisions are easy to make because a person has the experience and knowledge, and other decisions require extensive deliberation because of their complexity or because a person may lack knowledge in that area. Making effective decisions is not an inherent gift, but the process can be learned. The decision a person makes today will someday be the base from which to assess a new situation. PMID:2729970

  9. Exergaming in Older Adults: Movement Characteristics While Playing Stepping Games.

    PubMed

    Skjæret-Maroni, Nina; Vonstad, Elise K; Ihlen, Espen A F; Tan, Xiang-Chun; Helbostad, Jorunn L; Vereijken, Beatrix

    2016-01-01

    Despite frequent use of exergames in intervention studies to improve physical function in older adults, we lack knowledge about the movements performed during exergaming. This causes difficulties for interpreting results of intervention studies and drawing conclusions about the efficacy of exergames to exercise specific functions important for the elderly population. The aim of the current study was to investigate whether game and game level affect older adults' stepping and upper body movements while playing stepping exergames. A 3D-motion capture experiment was performed with 20 elderly (12 women and 8 men; age range 65-90 years), playing two exergames, The Mole from SilverFit and LightRace in YourShape: Fitness Evolved, on two difficulty levels, with five 1-min trials for each game and level. Reflective markers were placed on bases of first toe, heels, and lower back. Movement characteristics were analyzed with a linear mixed model. Results indicated that both game and game level affected movement characteristics. Participants took shorter steps and had lower step velocity when playing The Mole compared to LightRace, while The Mole prompted more variation in step length and step velocity. Compared to LightRace, The Mole elicited larger upper body movements in both ML- and AP-directions and participants' feet and upper body covered a larger area. Increasing difficulty level from Easy to Medium resulted in overall decrease of movement, except for number of steps and step speed when playing LightRace. Even with only two games, two levels, and five trials at each, this study indicates that the choice of exergame is not indifferent when aiming to exercise specific functions in older adults and that exergames need to be chosen and designed carefully based on the goals of the intervention. PMID:27445926

  10. Exergaming in Older Adults: Movement Characteristics While Playing Stepping Games

    PubMed Central

    Skjæret-Maroni, Nina; Vonstad, Elise K.; Ihlen, Espen A. F.; Tan, Xiang-Chun; Helbostad, Jorunn L.; Vereijken, Beatrix

    2016-01-01

    Despite frequent use of exergames in intervention studies to improve physical function in older adults, we lack knowledge about the movements performed during exergaming. This causes difficulties for interpreting results of intervention studies and drawing conclusions about the efficacy of exergames to exercise specific functions important for the elderly population. The aim of the current study was to investigate whether game and game level affect older adults’ stepping and upper body movements while playing stepping exergames. A 3D-motion capture experiment was performed with 20 elderly (12 women and 8 men; age range 65–90 years), playing two exergames, The Mole from SilverFit and LightRace in YourShape: Fitness Evolved, on two difficulty levels, with five 1-min trials for each game and level. Reflective markers were placed on bases of first toe, heels, and lower back. Movement characteristics were analyzed with a linear mixed model. Results indicated that both game and game level affected movement characteristics. Participants took shorter steps and had lower step velocity when playing The Mole compared to LightRace, while The Mole prompted more variation in step length and step velocity. Compared to LightRace, The Mole elicited larger upper body movements in both ML- and AP-directions and participants’ feet and upper body covered a larger area. Increasing difficulty level from Easy to Medium resulted in overall decrease of movement, except for number of steps and step speed when playing LightRace. Even with only two games, two levels, and five trials at each, this study indicates that the choice of exergame is not indifferent when aiming to exercise specific functions in older adults and that exergames need to be chosen and designed carefully based on the goals of the intervention. PMID:27445926

  11. Proteomic strategies in multiple sclerosis and its animal models

    PubMed Central

    Elkabes, Stella; Li, Hong

    2009-01-01

    The early and precise diagnosis, the prognosis, and the clinical management of multiple sclerosis, remain a considerable challenge. In recent years, the development of novel and powerful proteomic techniques prompted the use of these approaches for the search of unique biomarkers in the cerebrospinal fluid of multiple sclerosis patients. A few studies have also utilized proteomics to delineate the profile of differentially expressed proteins in animal models of the human disease in order to gain global insights into affected pathways. The identification of differentially expressed proteins may be an initial step in the discovery of novel targets and mechanisms that play critical roles in the pathology of multiple sclerosis. Based on these findings, future investigations may elucidate the events leading to demyelination, axonal damage, and neurodegeneration, providing better insights into mechanisms governing the onset and progression of the disease. Although these proteomic studies provide valuable information, they are also faced with a number of challenges. The present review discusses some of the strengths and limitations of proteomic investigations as applied to multiple sclerosis. PMID:19759847

  12. [Multiple apheresis].

    PubMed

    Coffe, C

    2007-05-01

    Multiple apheresis makes it possible to obtain at least two labile blood components from a single donor using a cell separator. It can be either multicomponent apheresis leading to the preparation of at least two different blood component types or red blood cell apheresis providing two identical red blood cell concentrates. These techniques available in addition to whole blood donation, are modifying collection strategies in many Etablissements Français du Sang and will contribute to improve stock logistics in the future. In areas with insufficient stock, these procedures will help achieve blood component self-sufficiency. The author first describes the principle underlying different--current or future--techniques as well as their advantages and drawbacks. He finally addresses the potential impact of these processes on the evolution of blood collection and the advantages to be gained. PMID:17521944

  13. Photovoltaic multiplicities

    NASA Astrophysics Data System (ADS)

    Queisser, Hans J.

    1997-04-01

    A multicell solar energy converter, produced in 1959/60 at the Shockley Transistor Corporation, is reviewed. The feasibility of this device, one of the first involving principles of Si integrated circuits, was demonstrated in anticipation of large-area Si sheets, to be pulled from Si/Pb binary melts. Secondly, the generation of multiple carrier pairs by absorption of merely one photon is discussed. Experiments on high-quality Si solar cells demonstrated this effect, which relies on inverse Auger generation. In principle, much higher maximal conversion efficiencies would be possible; novel criteria for materials optimization result. The new challenge of the inverse band structure problem arises. Finally, multistage optical transitions via deep centers in solar cells are briefly appraised.

  14. Psychopathology in Multiple Sclerosis

    PubMed Central

    Brüne, Martin; Juckel, Georg

    2009-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Demyelinization of nerve fibres not only affects the motor and sensory systems functionally, but may also cause psychopathological signs and symptoms. In addition to the psychiatric manifestations of MS, many patients have reactive psychological problems that are often hard to distinguish from the ‘organic’ causation of psychopathology. In any event, psychiatric comorbidity in MS deserves greater clinical attention than has been previously paid, because the presence of psychopathology may have deleterious effects on the disease process and impair coping with disability. PMID:21180640

  15. Neutron multiplicity analysis tool

    SciTech Connect

    Stewart, Scott L

    2010-01-01

    I describe the capabilities of the EXCOM (EXcel based COincidence and Multiplicity) calculation tool which is used to analyze experimental data or simulated neutron multiplicity data. The input to the program is the count-rate data (including the multiplicity distribution) for a measurement, the isotopic composition of the sample and relevant dates. The program carries out deadtime correction and background subtraction and then performs a number of analyses. These are: passive calibration curve, known alpha and multiplicity analysis. The latter is done with both the point model and with the weighted point model. In the current application EXCOM carries out the rapid analysis of Monte Carlo calculated quantities and allows the user to determine the magnitude of sample perturbations that lead to systematic errors. Neutron multiplicity counting is an assay method used in the analysis of plutonium for safeguards applications. It is widely used in nuclear material accountancy by international (IAEA) and national inspectors. The method uses the measurement of the correlations in a pulse train to extract information on the spontaneous fission rate in the presence of neutrons from ({alpha},n) reactions and induced fission. The measurement is relatively simple to perform and gives results very quickly ({le} 1 hour). By contrast, destructive analysis techniques are extremely costly and time consuming (several days). By improving the achievable accuracy of neutron multiplicity counting, a nondestructive analysis technique, it could be possible to reduce the use of destructive analysis measurements required in safeguards applications. The accuracy of a neutron multiplicity measurement can be affected by a number of variables such as density, isotopic composition, chemical composition and moisture in the material. In order to determine the magnitude of these effects on the measured plutonium mass a calculational tool, EXCOM, has been produced using VBA within Excel. This

  16. 48 CFR 52.214-25 - Step Two of Two-Step Sealed Bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  17. Adsorption on a stepped substrate

    NASA Astrophysics Data System (ADS)

    Merikoski, J.; Timonen, J.; Kaski, K.

    1994-09-01

    The effect of substrate steps on the adsorption of particles is considered. The problem is formulated as a lattice-gas model with nearest neighbor interactions and it is studied by a numerical transfer-matrix method. In particular, the influence of the substrate-induced row potential on adsorbed monolayers is discussed. It is found that strong row-transition-like features appear in the presence of a row potential and it is suggested that these may be seen in adsorption on vicinal faces.

  18. Lessons learned in stepped chute research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early research on stepped chutes focused on steep gravity style stepped chutes. Today, the research trend has shifted to stepped chutes applied to more moderate slopes like those for aging embankment dams. Research contributions have been made on hydraulic properties of stepped chutes including ai...

  19. Hydraulic Design of Stepped Spillways Workshop

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stepped chutes and spillways are commonly used for routing discharges during flood events. In addition, stepped chutes are used for overtopping protection of earthen embankments. Stepped spillways provide significant energy dissipation due to its stepped feature; as a result, the stilling basin as...

  20. Stepped conical zone plate antenna

    NASA Astrophysics Data System (ADS)

    Wiltse, James C.

    2001-07-01

    The Fresnel zone plate lens was invented and developed for optical frequencies. However, fabrication difficulties at the short optical wavelengths have prevented obtain good efficiencies. At longer microwave or millimeter-wavelengths fabrication is easier and phase correcting zone plate antennas have been used to obtain good efficiencies. This paper describes a new type of phase correcting zone plate having even better efficiency, namely a diffraction efficiency of 99 percent compared to a true lens, and an overall efficiency much better than a true lens. For the usual zone plate antenna employed at microwave or millimeter wavelengths, path length adjustment is accomplished by cutting different depths in a dielectric plate or by using two or more dielectrics having different dielectric constants. The new design uses a tilted cut in a dielectric plate, which more accurately matches the shape of a true lens and produces much lower phase error. The construction is still near and can be made for example, by a milling machine with a tilted bit. For a circular zone plate, the lens is a stepped conical or tapered shape. Because the phase steps are small, the far-field antenna pattern is excellent and sidelobe-levels are very low. Analysis of typical configurations will be given, showing that phase errors are small, lower than those for an eighth-wave corrected phase zone plate.

  1. One School...One Step.

    ERIC Educational Resources Information Center

    Westberry, Lee

    Overcoming parents' negative stereotypes of career and technical education (CTE) is the goal of the Business and Education Symposium (BES) at Stratford High School, Goose Creek, South Carolina. The BES program has these four main goals: (1) educate parents about the changing demands of the workforce, so as to affect student course selection; (2)…

  2. Unitary step of gliding machinery in Mycoplasma mobile

    PubMed Central

    Kinosita, Yoshiaki; Nakane, Daisuke; Sugawa, Mitsuhiro; Masaike, Tomoko; Mizutani, Kana; Miyata, Makoto; Nishizaka, Takayuki

    2014-01-01

    Among the bacteria that glide on substrate surfaces, Mycoplasma mobile is one of the fastest, exhibiting smooth movement with a speed of 2.0–4.5 μm⋅s−1 with a cycle of attachment to and detachment from sialylated oligosaccharides. To study the gliding mechanism at the molecular level, we applied an assay with a fluorescently labeled and membrane-permeabilized ghost model, and investigated the motility by high precision colocalization microscopy. Under conditions designed to reduce the number of motor interactions on a randomly oriented substrate, ghosts took unitary 70-nm steps in the direction of gliding. Although it remains possible that the stepping behavior is produced by multiple interactions, our data suggest that these steps are produced by a unitary gliding machine that need not move between sites arranged on a cytoskeletal lattice. PMID:24912194

  3. Multiple myeloma.

    PubMed

    Röllig, Christoph; Knop, Stefan; Bornhäuser, Martin

    2015-05-30

    Multiple myeloma is a malignant disease characterised by proliferation of clonal plasma cells in the bone marrow and typically accompanied by the secretion of monoclonal immunoglobulins that are detectable in the serum or urine. Increased understanding of the microenvironmental interactions between malignant plasma cells and the bone marrow niche, and their role in disease progression and acquisition of therapy resistance, has helped the development of novel therapeutic drugs for use in combination with cytostatic therapy. Together with autologous stem cell transplantation and advances in supportive care, the use of novel drugs such as proteasome inhibitors and immunomodulatory drugs has increased response rates and survival substantially in the past several years. Present clinical research focuses on the balance between treatment efficacy and quality of life, the optimum sequencing of treatment options, the question of long-term remission and potential cure by multimodal treatment, the pre-emptive treatment of high-risk smouldering myeloma, and the role of maintenance. Upcoming results of ongoing clinical trials, together with a pipeline of promising new treatments, raise the hope for continuous improvements in the prognosis of patients with myeloma in the future. PMID:25540889

  4. Multiple sclerosis.

    PubMed

    Filippi, Massimo; Preziosa, Paolo; Rocca, Maria A

    2016-01-01

    Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal. Several advanced MRI-based technologies have been applied to estimate overall MS burden in the different phases of the disease. Their use has allowed the heterogeneity of MS pathology in focal lesions, normal-appearing white matter and gray matter to be graded in vivo. Recently, additional features of MS pathology, including macrophage infiltration and abnormal iron deposition, have become quantifiable. All of this, combined with functional imaging techniques, is improving our understanding of the mechanisms associated with MS evolution. In the near future, the use of ultrahigh-field systems is likely to provide additional insight into disease pathophysiology. However, the utility of advanced MRI techniques in clinical trial monitoring and in assessing individual patients' response to treatment still needs to be assessed. PMID:27432676

  5. Executive Functions Underlying Multiplicative Reasoning: Problem Type Matters

    ERIC Educational Resources Information Center

    Agostino, Alba; Johnson, Janice; Pascual-Leone, Juan

    2010-01-01

    We investigated the extent to which inhibition, updating, shifting, and mental-attentional capacity ("M"-capacity) contribute to children's ability to solve multiplication word problems. A total of 155 children in Grades 3-6 (8- to 13-year-olds) completed a set of multiplication word problems at two levels of difficulty: one-step and multiple-step…

  6. Childhood Multiple Sclerosis: A Review

    ERIC Educational Resources Information Center

    Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan

    2006-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when…

  7. Moral transhumanism: the next step.

    PubMed

    Tennison, Michael N

    2012-08-01

    Although transhumanism offers hope for the transcendence of human biological limitations, it generates many intrinsic and consequential ethical concerns. The latter include issues such as the exacerbation of social inequalities and the exponentially increasing technological capacity to cause harm. To mitigate these risks, many thinkers have initiated investigations into the possibility of moral enhancement that could limit the power disparities facilitated by biotechnological enhancement. The arguments often focus on whether moral enhancement is morally permissible, or even obligatory, and remain largely in the realm of the hypothetical. This paper proposes that psilocybin may represent a viable, practical option for moral enhancement and that its further research in the context of moral psychology could comprise the next step in the development of moral transhumanism. PMID:22855738

  8. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-01-01

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth. PMID:27067000

  9. Neuregulin: First Steps Towards a Structure

    NASA Technical Reports Server (NTRS)

    Ferree, D. S.; Malone, C. C.; Karr, L. J.

    2003-01-01

    Neuregulins are growth factor domain proteins with diverse bioactivities, such as cell proliferation, receptor binding, and differentiation. Neureguh- 1 binds to two members of the ErbB class I tyrosine kinase receptors, ErbB3 and ErbB4. A number of human cancers overexpress the ErbB receptors, and neuregulin can modulate the growth of certain cancer types. Neuregulin-1 has been shown to promote the migration of invasive gliomas of the central nervous system. Neuregulin has also been implicated in schizophrenia, multiple sclerosis and abortive cardiac abnormalities. The full function of neuregulin-1 is not known. In this study we are inserting a cDNA clone obtained from American Type Culture Collection into E.coli expression vectors to express neuregulin- 1 protein. Metal chelate affinity chromatography is used for recombinant protein purification. Crystallization screening will proceed for X-ray diffraction studies following expression, optimization, and protein purification. In spite of medical and scholarly interest in the neuregulins, there are currently no high-resolution structures available for these proteins. Here we present the first steps toward attaining a high-resolution structure of neuregulin- 1, which will help enable us to better understand its function

  10. Keeping Track Every Step of the Way

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Knowledge Sharing Systems, Inc., a producer of intellectual assets management software systems for the federal government, universities, non-profit laboratories, and private companies, constructed and presently manages the NASA Technology Tracking System, also known as TechTracS. Under contract to Langley Research Center, TechTracS identifies and captures all NASA technologies, manages the patent prosecution process, and then tracks their progress en route to commercialization. The system supports all steps involved in various technology transfer activities, and is considered the premier intellectual asset management system used in the federal government today. NASA TechTracS consists of multiple relational databases and web servers, located at each of the 10 field centers, as well as NASA Headquarters. The system is capable of supporting the following functions: planning commercial technologies; commercialization activities; reporting new technologies and inventions; and processing and tracking intellectual property rights, licensing, partnerships, awards, and success stories. NASA TechTracS is critical to the Agency's ongoing mission to commercialize its revolutionary technologies in a variety of sectors within private industry, both aerospace and non- aerospace.

  11. Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice

    SciTech Connect

    Manenti, G.; Gariboldi, M.; Canzian, F.

    1994-09-01

    The C3H/He mouse represents a good experimental model of genetic predispositoin to hepatocellular tumor development. We analyzed an interspecific test-cross population of 106 urethane-treated male (C3H/He x Mus spretus) x C57BL/6J mice, typed with 222 genetic markers to locate precisely the hepatocellular tumor susceptibility (Hcs) loci. Three regions, on chromosomes 2, 5, and 19, showed a significant linkage with hepatocellular tumor development, as indicated by different quantitative indexes estimating liver tumor size. Liver tumor frequency was not genetically controlled. These loci are different from three other Hcs loci that we have previously mapped in an F2 progeny of the C3H/He mouse crossed with the resistant laboratory strain A/J. The present result indicates a multigenic model of inheritance for hepatocellular tumor susceptibility.

  12. A step-by-step procedure for pH model construction in aquatic systems

    NASA Astrophysics Data System (ADS)

    Hofmann, A. F.; Meysman, F. J. R.; Soetaert, K.; Middelburg, J. J.

    2008-02-01

    We present, by means of a simple example, a comprehensive step-by-step procedure to consistently derive a pH model of aquatic systems. As pH modelling is inherently complex, we make every step of the model generation process explicit, thus ensuring conceptual, mathematical, and chemical correctness. Summed quantities, such as total inorganic carbon and total alkalinity, and the influences of modeled processes on them are consistently derived. The different time scales of processes involved in the pH problem (biological and physical reactions: days; aquatic chemical reactions: fractions of seconds) give rise to a stiff equation system. Subsequent reformulations of the system reduce its stiffness, accepting higher non-linear algebraic complexity. The model is reformulated until numerically and computationally simple dynamical solutions, like a variation of the operator splitting approach (OSA) and the direct substitution approach (DSA), are obtained. As several solution methods are pointed out, connections between previous pH modelling approaches are established. The final reformulation of the system according to the DSA allows for quantification of the influences of kinetic processes on the rate of change of proton concentration in models containing multiple biogeochemical processes. These influences are calculated including the effect of re-equilibration of the system due to a set of acid-base reactions in local equilibrium. This possibility of quantifying influences of modeled processes on the pH makes the end-product of the described model generation procedure a powerful tool for understanding the internal pH dynamics of aquatic systems.

  13. Experiences with a single-step genome evaluation.

    PubMed

    Misztal, Ignacy; Aggrey, Samuel E; Muir, William M

    2013-09-01

    Genomic selection can be implemented based on the genomic relationship matrix (GBLUP) and can be combined with phenotypes from nongenotyped animals through the use of best linear unbiased prediction (BLUP). A common method to combine both sources of information involves multiple steps, but is difficult to use with complicated models and is nonoptimal. A simpler method, termed single-step GBLUP, or ssGBLUP, integrates the genomically derived relationships (G) with population-based pedigree relationships (A) into a combined relationship matrix (H) and allows for genomic selection in a single step. The ssGBLUP method is easy to implement and uses standard BLUP-based programs. Experiences with field data in chickens, pigs, and dairy indicate that ssGBLUP is more accurate yet much simpler than multi-step methods. The current limits of ssGBLUP are approximately 100,000 genotypes and 18 traits. Models involving 10 million animals have been run successfully. The inverse of H can also be used in existing programs for parameter estimationm, but a properly scaled G is needed for unbiased estimation. Also, as genomic predictions can be converted to SNP effects, ssGBLUP is useful for genomic-wide association studies. The single-step method for genomic selection translates the use of genomic information into standard BLUP, and variance-component estimation programs become a routine. PMID:23960138

  14. Multiple System Atrophy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy Information Page Condensed from Multiple System Atrophy ... Trials Organizations Publicaciones en Español What is Multiple System Atrophy? Multiple system atrophy (MSA) is a progressive ...

  15. [Optimization of one-step pelletization technology of Biqiu granules by Plackett-Burman design and Box-Behnken response surface methodology].

    PubMed

    Zhang, Yan-jun; Liu, Li-li; Hu, Jun-hua; Wu, Yun; Chao, En-xiang; Xiao, Wei

    2015-11-01

    First with the qualified rate of granules as the evaluation index, significant influencing factors were firstly screened by Plackett-Burman design. Then, with the qualified rate and moisture content as the evaluation indexes, significant factors that affect one-step pelletization technology were further optimized by Box-Behnken design; experimental data were imitated by multiple regression and second-order polynomial equation; and response surface method was used for predictive analysis of optimal technology. The best conditions were as follows: inlet air temperature of 85 degrees C, sample introduction speed of 33 r x min(-1), density of concrete 1. 10. One-step pelletization technology of Biqiu granules by Plackett-Burman design and Box-Behnken response surface methodology was stable and feasible with good predictability, which provided reliable basis for the industrialized production of Biqiu granules. PMID:27097415

  16. Entropic Step Doubling on W(430).

    NASA Astrophysics Data System (ADS)

    Conrad, Edward H.; Dey, Srijata; West, James; Kiriukhin, Sergei

    1996-03-01

    We present high resolution low energy electron diffraction (LEED) results for the W(430) surface. Unlike every other system studied to date, single atomic height steps on this surface become energetically unfavorable at elevated temperatures. Above 940 K, a two phase mixture of single and double height steps forms. The transition to double height steps is predicted on the basis of a simple model provided that unconventional defect energetics are invoked. Specifically, double height steps cost more than twice as much energy as single height steps, while kinks on the double height steps cost less energy than kinks on single height steps. Recent theoretical calculations independently confirm this energetics hierarchy. (W. Xu, J.B. Adams and T.L. Einstein (to be published).) The existence of the doubling transition sheds new light on previous self diffusion coefficient measurements for other stepped tungsten surfaces. (Y.M. Gong and R. Gomer, J. Chem. Phys. 88), 1359 (1988); 88, 1370 (1988).

  17. Science teacher enhancement project (STEP)

    SciTech Connect

    Ramsey, P.P.; Bowman, A.W.

    1994-12-31

    STEP, a National Science Foundation-funded initiative, forms an alliance between the three private Virginia Historically Black Colleges (Hampton University, Virginia Union University, and Saint Paul`s College) and nine school divisions, to increase the capabilities of middle school science teachers. Clearly articulated roles of each partner, and the inclusion of all partners in program planning has been invaluable. A unique feature of this project is the careful tailoring of the program to meet the needs of each school division, effected by ongoing communication between all of the partners. The program effected by ongoing communication between all of the partners. The program includes a Lead Teacher and Teacher Trainee component, and emphasizes science content, using a hands-on approach. In addition to science content, the Lead Teachers receive training in leadership, proposal writing, and pedagogical enrichment responsive to the curriculum change directions in science education, especially as it relates to minority and at-risk students. The enrichment is provided by university scientists and educators, through summer institutes and academic year workshops. Results include: use of new technologies in the classroom, cross-grade communication, use of university scientists as presenters for family science programs, and improved knowledge.

  18. Genetics Home Reference: multiple sulfatase deficiency

    MedlinePlus

    ... condition that mainly affects the brain, skin, and skeleton. Because the signs and symptoms of multiple sulfatase ... of cells in particular tissues, specifically the brain, skeleton, and skin, cause many of the signs and ...

  19. Genetics Home Reference: multiple pterygium syndrome

    MedlinePlus

    ... A side-to-side curvature of the spine ( scoliosis ) is sometimes seen. Affected individuals may also have ... Boston Children's Hospital: Respiratory Distress Boston Children's Hospital: Scoliosis in Children Cleveland Clinic: Scoliosis Disease InfoSearch: Multiple ...

  20. Ten Steps to Making Evaluation Matter

    ERIC Educational Resources Information Center

    Sridharan, Sanjeev; Nakaima, April

    2011-01-01

    This paper proposes ten steps to make evaluations matter. The ten steps are a combination of the usual recommended practice such as developing program theory and implementing rigorous evaluation designs with a stronger focus on more unconventional steps including developing learning frameworks, exploring pathways of evaluation influence, and…

  1. Ten steps to successful software process improvement

    NASA Technical Reports Server (NTRS)

    Kandt, R. K.

    2003-01-01

    This paper identifies ten steps for managing change that address organizational and cultural issues. Four of these steps are critical, that if not done, will almost guarantee failure. This ten-step program emphasizes the alignment of business goals, change process goals, and the work performed by the employees of an organization.

  2. 7 CFR 60.122 - Production step.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Production step. 60.122 Section 60.122 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... FOR FISH AND SHELLFISH General Provisions Definitions § 60.122 Production step. Production step...

  3. 7 CFR 65.230 - Production step.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Production step. 65.230 Section 65.230 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards..., PEANUTS, AND GINSENG General Provisions Definitions § 65.230 Production step. Production step means,...

  4. Stepping Up to Science and Math

    ERIC Educational Resources Information Center

    Goldston, Dee

    2004-01-01

    "Stepping Up to Science and Math" invites teachers to step back and rethink the way they teach both of these essential subjects. Then it illustrates how teachers can step up the pace with Standards-based activities that make learning more effective and efficient. (New lessons featuring gummy worms, school buses, or the planet Mars help teachers…

  5. STEPS: Moving from Welfare to Work.

    ERIC Educational Resources Information Center

    Vail, Ann; Cummings, Merrilyn; Kratzer, Connie; Galindo, Vickie

    Cooperative extension service faculty at New Mexico State University started the Steps to Employment and Personal Success (STEPS) program to help Temporary Assistance for Needy Families (TANF) clients qualify for and maintain full-time employment and strengthen their families for long-term success. Clients are referred to STEPS by New Mexico…

  6. CAD for 4-step braided fabric composites

    SciTech Connect

    Pandey, R.; Hahn, H.T.

    1994-12-31

    A general framework is provided to predict thermoelastic properties of three dimensional 4-step braided fabric composites. Three key steps involved are (1) the development of a CAD model for yarn architecture, (2) the extraction of a unit cell (3) the prediction of the thermoelastic properties based on micromechanics. Main features of each step are summarized and experimental correlations are provided in the paper.

  7. 7 CFR 65.230 - Production step.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Production step. 65.230 Section 65.230 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards..., PEANUTS, AND GINSENG General Provisions Definitions § 65.230 Production step. Production step means,...

  8. Improving Multiple Fault Diagnosability using Possible Conflicts

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew J.; Bregon, Anibal; Biswas, Gautam; Koutsoukos, Xenofon; Pulido, Belarmino

    2012-01-01

    Multiple fault diagnosis is a difficult problem for dynamic systems. Due to fault masking, compensation, and relative time of fault occurrence, multiple faults can manifest in many different ways as observable fault signature sequences. This decreases diagnosability of multiple faults, and therefore leads to a loss in effectiveness of the fault isolation step. We develop a qualitative, event-based, multiple fault isolation framework, and derive several notions of multiple fault diagnosability. We show that using Possible Conflicts, a model decomposition technique that decouples faults from residuals, we can significantly improve the diagnosability of multiple faults compared to an approach using a single global model. We demonstrate these concepts and provide results using a multi-tank system as a case study.

  9. STEP Tether Dynamics Preliminary Analysis

    NASA Technical Reports Server (NTRS)

    Glaese, John R.

    2000-01-01

    The General Tethered Object Simulation System (GTOSS) has been successfully converted to the PC environment. GTOSS has been run under Microsoft Windows 95, 98 and NT4.0 with no problems noted. Adaptation to the PC environment and definition of the 3 three body configuration required resizing some of the GTOSS internal data arrays. To allow studies of the tether dynamics accompanying electrodynamic thrust, a tether current flow model has also been developed for GTOSS. This model includes effects due to the earth's magnetic field and ionosphere, tether conductivity, temperature, motion, shape and available power. Sample cases have been defined for a proposed STEP-AIRSEDS (Space Transfer using Electrodynamic Propulsion-The Michigan Technic Corporation proposed tether missions for commercial applications) three body configuration. This required definition of a 6th power scenario for GTOSS. This power scenario allows a user to specify whether orbit raising or orbit lowering is to be performed by selecting the number of the tether. Orbit raising and orbit lowering sample cases have been run successfully. Results from these runs have been included in this report. Results have only been generated so far for a three body configuration. Only point end masses have been represented. No attitude dynamics have been included. Initial results suggest that tether current can have significant and detrimental effects on tether dynamics and provisions will have to be made for control of it. This control will have to be considered in connection with desired target orbits for electrodynamic thrusting, as well as end body attitude control, momentum management of proposed control moment gyros, solar array pointing. All of these items will interact and thus, any system simulation will have to have each of these effects modeled in sufficient detail to display these interactions.

  10. Dynamic emotional processing in experiential therapy: two steps forward, one step back.

    PubMed

    Pascual-Leone, Antonio

    2009-02-01

    The study of dynamic and nonlinear change has been a valuable development in psychotherapy process research. However, little advancement has been made in describing how moment-by-moment affective processes contribute to larger units of change. The purpose of this study was to examine observable moment-by-moment sequences in emotional processing as they occurred within productive sessions of experiential therapy. This article further tested A. Pascual-Leone and L. S. Greenberg's (2007) model of emotional processing through a reanalysis of their data sample of 34 sessions in which clients presented with global distress: 17 that ended in poor in-session events and 17 that ended in good in-session events. Current analyses used univariate and bootstrapping statistical methods to examine how dynamic temporal patterns in clients' emotion accumulated moment-by-moment to produce in-session gains in emotional processing. Results show that effective emotional processing was simultaneously associated with steady improvement according to the model as well as increased emotional range. Consequentially, good events were shown to occur in a 2-steps-forward, 1-step-back fashion. Finally, good events were also shown to have progressively shortened emotional collapses, whereas the opposite was true for poor in-session events. PMID:19170458

  11. Solar array stepping to minimize array excitation

    NASA Technical Reports Server (NTRS)

    Bhat, Mahabaleshwar K. P. (Inventor); Liu, Tung Y. (Inventor); Plescia, Carl T. (Inventor)

    1989-01-01

    Mechanical oscillations of a mechanism containing a stepper motor, such as a solar-array powered spacecraft, are reduced and minimized by the execution of step movements in pairs of steps, the period between steps being equal to one-half of the period of torsional oscillation of the mechanism. Each pair of steps is repeated at needed intervals to maintain desired continuous movement of the portion of elements to be moved, such as the solar array of a spacecraft. In order to account for uncertainty as well as slow change in the period of torsional oscillation, a command unit may be provided for varying the interval between steps in a pair.

  12. Biophysical Interactions within Step-Pool Mountain Streams Following Wildfire

    NASA Astrophysics Data System (ADS)

    Parker, A.; Chin, A.; O'Dowd, A. P.

    2014-12-01

    Recovery of riverine ecosystems following disturbance is driven by a variety of interacting processes. Wildfires pose increasing disturbances to riverine landscapes, with rising frequencies and magnitudes owing to warming climates and increased fuel loads. The effects of wildfire include loss of vegetation, elevated runoff and flash floods, erosion and deposition, and changing biological habitats and communities. Understanding process interactions in post-fire landscapes is increasingly urgent for successful management and restoration of affected ecosystems. In steep channels, steps and pools provide prominent habitats for organisms and structural integrity in high energy environments. Step-pools are typically stable, responding to extreme events with recurrence intervals often exceeding 50 years. Once wildfire occurs, however, intensification of post-fire flood events can potentially overpower the inherent stability of these systems, with significant consequences for aquatic life and human well-being downstream. This study examined the short-term response of step-pool streams following the 2012 Waldo Canyon Fire in Colorado. We explored interacting feedbacks among geomorphology, hydrology, and ecology in the post-fire environment. At selected sites with varying burn severity, we established baseline conditions immediately after the fire with channel surveys, biological assessment using benthic macroinvertebrates, sediment analysis including pebble counts, and precipitation gauging. Repeat measurements after major storm events over several years enabled analysis of the interacting feedbacks among post-fire processes. We found that channels able to retain the step-pool structure changed less and facilitated recovery more readily. Step habitats maintained higher percentages of sensitive macroinvertebrate taxa compared to pools through post-fire floods. Sites burned with high severity experienced greater reduction in the percentage of sensitive taxa. The decimation of

  13. Learning to track multiple targets.

    PubMed

    Liu, Xiao; Tao, Dacheng; Song, Mingli; Zhang, Luming; Bu, Jiajun; Chen, Chun

    2015-05-01

    Monocular multiple-object tracking is a fundamental yet under-addressed computer vision problem. In this paper, we propose a novel learning framework for tracking multiple objects by detection. First, instead of heuristically defining a tracking algorithm, we learn that a discriminative structure prediction model from labeled video data captures the interdependence of multiple influence factors. Given the joint targets state from the last time step and the observation at the current frame, the joint targets state at the current time step can then be inferred by maximizing the joint probability score. Second, our detection results benefit from tracking cues. The traditional detection algorithms need a nonmaximal suppression postprocessing to select a subset from the total detection responses as the final output and a large number of selection mistakes are induced, especially under a congested circumstance. Our method integrates both detection and tracking cues. This integration helps to decrease the postprocessing mistake risk and to improve performance in tracking. Finally, we formulate the entire model training into a convex optimization problem and estimate its parameters using the cutting plane optimization. Experiments show that our method performs effectively in a large variety of scenarios, including pedestrian tracking in crowd scenes and vehicle tracking in congested traffic. PMID:25051561

  14. Spatial layout affects speed discrimination

    NASA Technical Reports Server (NTRS)

    Verghese, P.; Stone, L. S.

    1997-01-01

    We address a surprising result in a previous study of speed discrimination with multiple moving gratings: discrimination thresholds decreased when the number of stimuli was increased, but remained unchanged when the area of a single stimulus was increased [Verghese & Stone (1995). Vision Research, 35, 2811-2823]. In this study, we manipulated the spatial- and phase relationship between multiple grating patches to determine their effect on speed discrimination thresholds. In a fusion experiment, we merged multiple stimulus patches, in stages, into a single patch. Thresholds increased as the patches were brought closer and their phase relationship was adjusted to be consistent with a single patch. Thresholds increased further still as these patches were fused into a single patch. In a fission experiment, we divided a single large patch into multiple patches by superimposing a cross with luminance equal to that of the background. Thresholds decreased as the large patch was divided into quadrants and decreased further as the quadrants were maximally separated. However, when the cross luminance was darker than the background, it was perceived as an occluder and thresholds, on average, were unchanged from that for the single large patch. A control experiment shows that the observed trend in discrimination thresholds is not due to the differences in perceived speed of the stimuli. These results suggest that the parsing of the visual image into entities affects the combination of speed information across space, and that each discrete entity effectively provides a single independent estimate of speed.

  15. Mixed Mode Matrix Multiplication

    SciTech Connect

    Meng-Shiou Wu; Srinivas Aluru; Ricky A. Kendall

    2004-09-30

    In modern clustering environments where the memory hierarchy has many layers (distributed memory, shared memory layer, cache,...), an important question is how to fully utilize all available resources and identify the most dominant layer in certain computations. When combining algorithms on all layers together, what would be the best method to get the best performance out of all the resources we have? Mixed mode programming model that uses thread programming on the shared memory layer and message passing programming on the distributed memory layer is a method that many researchers are using to utilize the memory resources. In this paper, they take an algorithmic approach that uses matrix multiplication as a tool to show how cache algorithms affect the performance of both shared memory and distributed memory algorithms. They show that with good underlying cache algorithm, overall performance is stable. When underlying cache algorithm is bad, superlinear speedup may occur, and an increasing number of threads may also improve performance.

  16. Affective processing requires awareness.

    PubMed

    Lähteenmäki, Mikko; Hyönä, Jukka; Koivisto, Mika; Nummenmaa, Lauri

    2015-04-01

    Studies using backward masked emotional stimuli suggest that affective processing may occur outside visual awareness and imply primacy of affective over semantic processing, yet these experiments have not strictly controlled for the participants' awareness of the stimuli. Here we directly compared the primacy of affective versus semantic categorization of biologically relevant stimuli in 5 experiments (n = 178) using explicit (semantic and affective discrimination; Experiments 1-3) and implicit (semantic and affective priming; Experiments 4-5) measures. The same stimuli were used in semantic and affective tasks. Visual awareness was manipulated by varying exposure duration of the masked stimuli, and subjective level of stimulus awareness was measured after each trial using a 4-point perceptual awareness scale. When participants reported no awareness of the stimuli, semantic and affective categorization were at chance level and priming scores did not differ from zero. When participants were even partially aware of the stimuli, (a) both semantic and affective categorization could be performed above chance level with equal accuracy, (b) semantic categorization was faster than affective categorization, and (c) both semantic and affective priming were observed. Affective categorization speed was linearly dependent on semantic categorization speed, suggesting dependence of affective processing on semantic recognition. Manipulations of affective and semantic categorization tasks revealed a hierarchy of categorization operations beginning with basic-level semantic categorization and ending with superordinate level affective categorization. We conclude that both implicit and explicit affective and semantic categorization is dependent on visual awareness, and that affective recognition follows semantic categorization. PMID:25559654

  17. Composite-step product methods for solving nonsymmetric linear systems

    SciTech Connect

    Chan, T.F.; Szeto, T.

    1994-12-31

    The Biconjugate Gradient (BCG) algorithm is the {open_quotes}natural{close_quotes} generalization of the classical Conjugate Gradient method to nonsymmetric linear systems. It is an attractive method because of its simplicity and its good convergence properties. Unfortunately, BCG suffers from two kinds of breakdowns (divisions by 0): one due to the non-existence of the residual polynomial, and the other due to a breakdown in the recurrence relationship used. There are many look-ahead techniques in existence which are designed to handle these breakdowns. Although the step size needed to overcome an exact breakdown can be computed in principle, these methods can unfortunately be quite complicated for handling near breakdowns since the sizes of the look-ahead steps are variable (indeed, the breakdowns can be incurable). Recently, Bank and Chan introduced the Composite Step Biconjugate Gradient (CSBCG) algorithm, an alternative which cures only the first of the two breakdowns mentioned by skipping over steps for which the BCG iterate is not defined. This is done with a simple modification of BCG which needs only a maximum look-ahead step size of 2 to eliminate the (near) breakdown and to smooth the sometimes erratic convergence of BCG. Thus, instead of a more complicated (but less prone to breakdown) version, CSBCG cures only one kind of breakdown, but does so with a minimal modification to the usual implementation of BCG in the hope that its empirically observed stability will be inherited. The authors note, then, that the Composite Step idea can be incorporated anywhere the BCG polynomial is used; in particular, in product methods such as CGS, Bi-CGSTAB, and TFQMR. Doing this not only cures the breakdown mentioned above, but also takes on the advantages of these product methods, namely, no multiplications by the transpose matrix and a faster convergence rate than BCG.

  18. Multiple Assessments for Multiple Intelligences. Third Edition.

    ERIC Educational Resources Information Center

    Bellanca, James; Chapman, Carolyn; Swartz, Elizabeth

    This book is designed to align assessment with instructional practices that promote the development of the multiple intelligences outlined by Howard Gardner. To facilitate the use of multiple assessments for the multiple intelligences, the information in this book is transferable to the classroom. The book explains how a teacher can design…

  19. Step barrier system multiview glassless 3D display

    NASA Astrophysics Data System (ADS)

    Mashitani, Ken; Hamagishi, Goro; Higashino, Masahiro; Ando, Takahisa; Takemoto, Satoshi

    2004-05-01

    The step barrier technology with multiple parallax images has overcome the problem of conventional parallax barrier system that the image quality of each image deteriorates only in the horizontal direction. The step barrier distributes the resolution problem both to the horizontal and the vertical directions. The system has a simple structure, which consists of a flat-panel display and a step barrier. The apertures of the step barrier are not stripes but tiny rectangles that are arranged in the shape of stairs, and the sub-pixels of each image have the same arrangement. And three image processes for the system applicable to computer graphics and real image have been proposed. Then, two types of 3-D displays were developed, 22-inch model and 50-inch model. The 22-inch model employs a very high-definition liquid crystal display of 3840 x 2400 pixels. The number of parallax images is seven and the resolution of one image is 1646 x 800. The 50-inch model has four viewing points on the plasma display panel of 1280 x 768 pixels. It can provide stereoscopic animations and the resolution of one image is 960 x 256 pixels. Moreover, the structural or electric 2-D 3-D compatible system was developed.

  20. Applications of step-selection functions in ecology and conservation.

    PubMed

    Thurfjell, Henrik; Ciuti, Simone; Boyce, Mark S

    2014-01-01

    Recent progress in positioning technology facilitates the collection of massive amounts of sequential spatial data on animals. This has led to new opportunities and challenges when investigating animal movement behaviour and habitat selection. Tools like Step Selection Functions (SSFs) are relatively new powerful models for studying resource selection by animals moving through the landscape. SSFs compare environmental attributes of observed steps (the linear segment between two consecutive observations of position) with alternative random steps taken from the same starting point. SSFs have been used to study habitat selection, human-wildlife interactions, movement corridors, and dispersal behaviours in animals. SSFs also have the potential to depict resource selection at multiple spatial and temporal scales. There are several aspects of SSFs where consensus has not yet been reached such as how to analyse the data, when to consider habitat covariates along linear paths between observations rather than at their endpoints, how many random steps should be considered to measure availability, and how to account for individual variation. In this review we aim to address all these issues, as well as to highlight weak features of this modelling approach that should be developed by further research. Finally, we suggest that SSFs could be integrated with state-space models to classify behavioural states when estimating SSFs. PMID:25520815

  1. Time scaling relations for step bunches from models with step-step attractions (B1-type models)

    NASA Astrophysics Data System (ADS)

    Krasteva, A.; Popova, H.; Akutsu, N.; Tonchev, V.

    2016-03-01

    The step bunching instability is studied in three models of step motion defined in terms of ordinary differential equations (ODE). The source of instability in these models is step-step attraction, it is opposed by step-step repulsion and the developing surface patterns reflect the balance between the two. The first model, TE2, is a generalization of the seminal model of Tersoff et al. (1995). The second one, LW2, is obtained from the model of Liu and Weeks (1998) using the repulsions term to construct the attractions one with retained possibility to change the parameters in the two independently. The third model, MM2, is a minimal one constructed ad hoc and in this article it plays a central role. New scheme for scaling the ODE in vicinal studies is applied towards deciphering the pre-factors in the time-scaling relations. In all these models the patterned surface is self-similar - only one length scale is necessary to describe its evolution (hence B1-type). The bunches form finite angles with the terraces. Integrating numerically the equations for step motion and changing systematically the parameters we obtain the overall dependence of time-scaling exponent β on the power of step-step attractions p as β = 1/(3+p) for MM2 and hypothesize based on restricted set of data that it is β = 1/(5+p) for LW2 and TE2.

  2. Factors affecting the heart rate during self-paced walking.

    PubMed

    Bassey, E J; Macdonald, I A; Patrick, J M

    1982-01-01

    The results of 277 self-paced walking tests have been analysed for the effects of body composition, sex and age using step-up multiple regression analysis. Equations are given for the influence of the significant factors on chosen walking speeds and on heart rate (fc) (standardised at 4.8 km . h-1 by interpolation from points recorded at three walking speeds). The basic equations are: Normal speed (km . h-1) = 1.72 + 2.13 stature (m) - 0.008 age (years) Fast speed (km . h-1) = 0.54 + 3.69 stature (m) - 0.016 age (years) For men: fc4.8 (beat . min-1) = 161 - 50.7 stature (m) + 0.223 body weight (kg) For women: fc4.8 (beat . min-1) = 161 - 50.7 stature (m) + 0.223 body weight (kg) + 4.43 The significant factors affecting freely chosen walking speeds are stature and age. When estimates of body composition are available, percentage fat is found to be the most influential single factor affecting fc, while sex no longer has a significant effect, and age now has a negative influence. When allowance is made for these factors the effects of customary physical activity can be seen more clearly. PMID:7199445

  3. Motivational factors and negative affectivity as predictors of alcohol craving.

    PubMed

    Pombo, Samuel; Luísa Figueira, M; Walter, Henriette; Lesch, Otto

    2016-09-30

    Craving is thought to play an important role in alcohol use disorders. The recent inclusion of "craving" as a formal diagnostic symptom calls for further investigation of this subjective phenomenon with multiple dimensions. Considering that alcohol-dependent patients compensate negative physical/emotional states with alcohol, the aim of this study is to investigate alcohol craving and its correlation with drinking measures and affective personality dimensions. A sample of 135 alcohol-dependent patients (104 males and 31 females) was collected from a clinical setting. Subjects self-rated their cravings (Penn Alcohol Craving Scale) and the stage of change. Several personality scales were also administered. Craving was related to drinking status, abstinence time, age, and taking steps. After controlling for these conditions, psychological characteristics related to low self-concept, neuroticism, cyclothymic affective temperament, depression, and hostility were found to be predictors of craving in sober alcohol-dependent patients. Our results support craving as a component of the phenomenology of alcohol dependence and highlight the presence of unpleasant feelings as predictors of craving in sober alcohol-dependent patients without co-occurring psychiatric conditions. The predisposition to experience negative emotions may induce a stronger craving response and increase the likelihood of a first drink and a subsequent loss of control. PMID:27367491

  4. Identification of loci affecting flavour volatile emissions in tomato fruits.

    PubMed

    Tieman, Denise M; Zeigler, Michelle; Schmelz, Eric A; Taylor, Mark G; Bliss, Peter; Kirst, Matias; Klee, Harry J

    2006-01-01

    Fresh tomato fruit flavour is the sum of the interaction between sugars, acids, and a set of approximately 30 volatile compounds synthesized from a diverse set of precursors, including amino acids, lipids, and carotenoids. Some of these volatiles impart desirable qualities while others are negatively perceived. As a first step to identify the genes responsible for the synthesis of flavour-related chemicals, an attempt was made to identify loci that influence the chemical composition of ripe fruits. A genetically diverse but well-defined Solanum pennellii IL population was used. Because S. pennellii is a small green-fruited species, this population exhibits great biochemical diversity and is a rich source of genes affecting both fruit development and chemical composition. This population was used to identify multiple loci affecting the composition of chemicals related to flavour. Twenty-five loci were identified that are significantly altered in one or more of 23 different volatiles and four were altered in citric acid content. It was further shown that emissions of carotenoid-derived volatiles were directly correlated with the fruit carotenoid content. Linked molecular markers should be useful for breeding programmes aimed at improving fruit flavour. In the longer term, the genes responsible for controlling the levels of these chemicals will be important tools for understanding the complex interactions that ultimately integrate to provide the unique flavour of a tomato. PMID:16473892

  5. Steps Toward Optimal Competitive Scheduling

    NASA Technical Reports Server (NTRS)

    Frank, Jeremy; Crawford, James; Khatib, Lina; Brafman, Ronen

    2006-01-01

    This paper is concerned with the problem of allocating a unit capacity resource to multiple users within a pre-defined time period. The resource is indivisible, so that at most one user can use it at each time instance. However, different users may use it at different times. The users have independent, se@sh preferences for when and for how long they are allocated this resource. Thus, they value different resource access durations differently, and they value different time slots differently. We seek an optimal allocation schedule for this resource. This problem arises in many institutional settings where, e.g., different departments, agencies, or personal, compete for a single resource. We are particularly motivated by the problem of scheduling NASA's Deep Space Satellite Network (DSN) among different users within NASA. Access to DSN is needed for transmitting data from various space missions to Earth. Each mission has different needs for DSN time, depending on satellite and planetary orbits. Typically, the DSN is over-subscribed, in that not all missions will be allocated as much time as they want. This leads to various inefficiencies - missions spend much time and resource lobbying for their time, often exaggerating their needs. NASA, on the other hand, would like to make optimal use of this resource, ensuring that the good for NASA is maximized. This raises the thorny problem of how to measure the utility to NASA of each allocation. In the typical case, it is difficult for the central agency, NASA in our case, to assess the value of each interval to each user - this is really only known to the users who understand their needs. Thus, our problem is more precisely formulated as follows: find an allocation schedule for the resource that maximizes the sum of users preferences, when the preference values are private information of the users. We bypass this problem by making the assumptions that one can assign money to customers. This assumption is reasonable; a

  6. Contribution of lower limb eccentric work and different step responses to balance recovery among older adults.

    PubMed

    Nagano, Hanatsu; Levinger, Pazit; Downie, Calum; Hayes, Alan; Begg, Rezaul

    2015-09-01

    Falls during walking reflect susceptibility to balance loss and the individual's capacity to recover stability. Balance can be recovered using either one step or multiple steps but both responses are impaired with ageing. To investigate older adults' (n=15, 72.5±4.8 yrs) recovery step control a tether-release procedure was devised to induce unanticipated forward balance loss. Three-dimensional position-time data combined with foot-ground reaction forces were used to measure balance recovery. Dependent variables were; margin of stability (MoS) and available response time (ART) for spatial and temporal balance measures in the transverse and sagittal planes; lower limb joint angles and joint negative/positive work; and spatio-temporal gait parameters. Relative to multi-step responses, single-step recovery was more effective in maintaining balance, indicated by greater MoS and longer ART. MoS in the sagittal plane measure and ART in the transverse plane distinguished single step responses from multiple steps. When MoS and ART were negative (<0), balance was not secured and additional steps would be required to establish the new base of support for balance recovery. Single-step responses demonstrated greater step length and velocity and when the recovery foot landed, greater centre of mass downward velocity. Single-step strategies also showed greater ankle dorsiflexion, increased knee maximum flexion and more negative work at the ankle and knee. Collectively these findings suggest that single-step responses are more effective in forward balance recovery by directing falling momentum downward to be absorbed as lower limb eccentric work. PMID:26077787

  7. Influence of Allosteric Regulators on Individual Steps in the Reaction Catalyzed by Mycobacterium tuberculosis 2-Hydroxy-3-oxoadipate Synthase*

    PubMed Central

    Balakrishnan, Anand; Jordan, Frank; Nathan, Carl F.

    2013-01-01

    Allosteric regulation often controls key branch points in metabolic processes. Mycobacterium tuberculosis 2-hydroxy-3-oxoadipate synthase (HOAS), a thiamin diphosphate (ThDP)-dependent enzyme, produces 2-hydroxy-3-oxoadipate using 2-ketoglutarate and glyoxylate. The proposed chemical mechanism in analogy with other ThDP-dependent carboligases involves multiple ThDP-bound covalent intermediates. Acetyl coenzyme A is an activator, and GarA, a forkhead association domain-containing protein known to regulate glutamate metabolism, is an allosteric inhibitor of HOAS. Steady state kinetics using assays to study the first half and the full catalytic cycle suggested that the regulators act at different steps in the overall mechanism. To explore the modes of regulation and to test the effects on individual catalytic steps, we performed circular dichroism (CD) studies using a non-decarboxylatable 2-ketoglutarate analog and determined the distribution of ThDP-bound covalent intermediates during the steady state of the HOAS reaction using one-dimensional 1H gradient carbon heteronuclear single quantum coherence NMR. The results suggest that acetyl coenzyme A acts as a mixed V and K type activator and predominantly affects the predecarboxylation steps. GarA does not inhibit the formation of the predecarboxylation analog and does not affect the accumulation of the postdecarboxylation covalent intermediate derived from 2-ketoglutarate; however, it decreases the abundance of the product ThDP adduct in the HOAS pathway. Thus, the two regulators act on different halves of the catalytic cycle in an unusual regulatory regime. PMID:23760263

  8. Multiple trellis coded modulation

    NASA Technical Reports Server (NTRS)

    Simon, Marvin K. (Inventor); Divsalar, Dariush (Inventor)

    1990-01-01

    A technique for designing trellis codes to minimize bit error performance for a fading channel. The invention provides a criteria which may be used in the design of such codes which is significantly different from that used for average white Gaussian noise channels. The method of multiple trellis coded modulation of the present invention comprises the steps of: (a) coding b bits of input data into s intermediate outputs; (b) grouping said s intermediate outputs into k groups of s.sub.i intermediate outputs each where the summation of all s.sub.i,s is equal to s and k is equal to at least 2; (c) mapping each of said k groups of intermediate outputs into one of a plurality of symbols in accordance with a plurality of modulation schemes, one for each group such that the first group is mapped in accordance with a first modulation scheme and the second group is mapped in accordance with a second modulation scheme; and (d) outputting each of said symbols to provide k output symbols for each b bits of input data.

  9. Elastic cost of silicon step rebonding

    NASA Astrophysics Data System (ADS)

    Leroy, F.; Garreau, Y.; Cheynis, F.; Croset, B.; Coati, A.; Müller, P.; Prévot, G.

    2016-01-01

    We study by grazing incidence x-ray diffraction the strain field induced by periodic double steps on a Si(1 1 15) surface that is a vicinal of a Si(001) surface misoriented by 5 .4∘ towards the <110 > direction. The best fit of the experimental structure factors is reached on the basis of the rebonded DB step edge model and the displacement field is well characterized assuming that steps are described by parallel rows of extended buried elastic dipoles. The dipole characteristics are the dipole position with respect to the step edge, the dipole amplitude (2.0 ±0.5 nN), and the lever arm Ω =5 .3∘ and force Φ =3 .7∘ orientations. We show that the dipole is dominated by a large stretch component localized between the lower and the upper corners of the step, which we assign to the presence of the rebonded atom at the step.

  10. Control Circuit For Two Stepping Motors

    NASA Technical Reports Server (NTRS)

    Ratliff, Roger; Rehmann, Kenneth; Backus, Charles

    1990-01-01

    Control circuit operates two independent stepping motors, one at a time. Provides following operating features: After selected motor stepped to chosen position, power turned off to reduce dissipation; Includes two up/down counters that remember at which one of eight steps each motor set. For selected motor, step indicated by illumination of one of eight light-emitting diodes (LED's) in ring; Selected motor advanced one step at time or repeatedly at rate controlled; Motor current - 30 mA at 90 degree positions, 60 mA at 45 degree positions - indicated by high or low intensity of LED that serves as motor-current monitor; Power-on reset feature provides trouble-free starts; To maintain synchronism between control circuit and motors, stepping of counters inhibited when motor power turned off.

  11. Random walk with an exponentially varying step

    NASA Astrophysics Data System (ADS)

    de La Torre, A. C.; Maltz, A.; Mártin, H. O.; Catuogno, P.; García-Mata, I.

    2000-12-01

    A random walk with exponentially varying step, modeling damped or amplified diffusion, is studied. Each step is equal to the previous one multiplied by a step factor s (01/s relating different processes. For s<1/2 and s>2, the process is retrodictive (i.e., every final position can be reached by a unique path) and the set of all possible final points after infinite steps is fractal. For step factors in the interval [1/2,2], some cases result in smooth density distributions, other cases present overlapping self-similarity and there are values of the step factor for which the distribution is singular without a density function.

  12. Affect Regulation and Purging: An Ecological Momentary Assessment Study in Purging Disorder

    PubMed Central

    Haedt-Matt, Alissa A.; Keel, Pamela K.

    2015-01-01

    Research suggests that affect may play an important role in the propensity to purge among women with Purging Disorder (PD). However, prior work has been constrained to cross-sectional or laboratory designs which impact temporal interpretations and ecological validity. This study examined the role of negative affect (NA) and positive affect (PA) in triggering and maintaining purging in PD using ecological momentary assessment. Women with PD (N=24) made multiple daily ratings of affect and behavior for two weeks. Multilevel models examined associations between affect and purging at different levels of analysis, including a novel analytic approach to address the specificity of changes in affect relative to purging behavior by comparing trajectories of change on purge versus non-purge days. For trajectories of affect over time, NA increased before purging and decreased following purging on purge days; however, only the decrease in NA following purging was significantly different from the trajectory of NA on non-purge days. Conversely, PA failed to increase before purging on purge days compared to a matched time-point on non-purge days. These findings suggest unique roles of PA in triggering and NA in maintaining purging in PD and support models in which purging functions to regulate affect. For comparisons of ratings before and after purging, NA increased and PA decreased after purging, highlighting how different analytic strategies produce different findings requiring integration into affect regulation models. These data provide insight into why women with PD purge after consuming normal amounts of food, a crucial first step for developing effective interventions. PMID:25688426

  13. Sage Simulation Model for Technology Demonstration Convertor by a Step-by-Step Approach

    NASA Technical Reports Server (NTRS)

    Demko, Rikako; Penswick, L. Barry

    2006-01-01

    The development of a Stirling model using the 1-D Saga design code was completed using a step-by-step approach. This is a method of gradually increasing the complexity of the Saga model while observing the energy balance and energy losses at each step of the development. This step-by-step model development and energy-flow analysis can clarify where the losses occur, their impact, and suggest possible opportunities for design improvement.

  14. Surface-Step-Induced Oscillatory Oxide Growth

    NASA Astrophysics Data System (ADS)

    Li, Liang; Luo, Langli; Ciston, Jim; Saidi, Wissam A.; Stach, Eric A.; Yang, Judith C.; Zhou, Guangwen

    2014-09-01

    We report in situ atomic-resolution transmission electron microscopy observations of the oxidation of stepped Cu surfaces. We find that the presence of surface steps both inhibits oxide film growth and leads to the oxide decomposition, thereby resulting in oscillatory oxide film growth. Using atomistic simulations, we show that the oscillatory oxide film growth is induced by oxygen adsorption on the lower terrace along the step edge, which destabilizes the oxide film formed on the upper terrace.

  15. Multi-step contrast sensitivity gauge

    SciTech Connect

    Quintana, Enrico C; Thompson, Kyle R; Moore, David G; Heister, Jack D; Poland, Richard W; Ellegood, John P; Hodges, George K; Prindville, James E

    2014-10-14

    An X-ray contrast sensitivity gauge is described herein. The contrast sensitivity gauge comprises a plurality of steps of varying thicknesses. Each step in the gauge includes a plurality of recesses of differing depths, wherein the depths are a function of the thickness of their respective step. An X-ray image of the gauge is analyzed to determine a contrast-to-noise ratio of a detector employed to generate the image.

  16. Revisiting "how many steps are enough?".

    PubMed

    Tudor-Locke, Catrine; Hatano, Yoshiro; Pangrazi, Robert P; Kang, Minsoo

    2008-07-01

    With continued widespread acceptance of pedometers by both researchers and practitioners, evidence-based steps/day indices are needed to facilitate measurement and motivation applications of physical activity (PA) in public health. Therefore, the purpose of this article is to reprise, update, and extend the current understanding of dose-response relationships in terms of pedometer-determined PA. Any pedometer-based PA guideline presumes an accurate and standardized measure of steps; at this time, industry standards establishing quality control of instrumentation is limited to Japan where public health pedometer applications and the 10,000 steps.d slogan are traceable to the 1960s. Adult public health guidelines promote > or =30 min of at least moderate-intensity daily PA, and this translates to 3000-4000 steps if they are: 1) at least moderate intensity (i.e., > or =100 steps.min); 2) accumulated in at least 10-min bouts; and 3) taken over and above some minimal level of PA (i.e., number of daily steps) below which individuals might be classified as sedentary. A zone-based hierarchy is useful for both measurement and motivation purposes in adults: 1) <5000 steps.d (sedentary); 2) 5000-7499 steps.d (low active); 3) 7500-9999 steps.d (somewhat active); 4) > or =10,000-12,499 steps.d (active); and 5) > or =12,500 steps.d (highly active). Evidence to support youth-specific cutoff points is emerging. Criterion-referenced approaches based on selected health outcomes present the potential for advancing evidence-based steps/day standards in both adults and children from a measurement perspective. A tradeoff that needs to be acknowledged and considered is the impact on motivation when evidence-based cutoff points are interpreted by individuals as unattainable goals. PMID:18562971

  17. One step geometrical calibration method for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Díaz Díaz, Jesús; Stritzel, Jenny; Rahlves, Maik; Majdani, Omid; Reithmeier, Eduard; Ortmaier, Tobias; Roth, Bernhard

    2016-01-01

    We present a novel one-step calibration methodology for geometrical distortion correction for optical coherence tomography (OCT). A calibration standard especially designed for OCT is introduced, which consists of an array of inverse pyramidal structures. The use of multiple landmarks situated on four different height levels on the pyramids allow performing a 3D geometrical calibration. The calibration procedure itself is based on a parametric model of the OCT beam propagation. It is validated by experimental results and enables the reduction of systematic errors by more than one order of magnitude. In future, our results can improve OCT image reconstruction and interpretation for medical applications such as real time monitoring of surgery.

  18. Integration of multiple view plus depth data for free viewpoint 3D display

    NASA Astrophysics Data System (ADS)

    Suzuki, Kazuyoshi; Yoshida, Yuko; Kawamoto, Tetsuya; Fujii, Toshiaki; Mase, Kenji

    2014-03-01

    This paper proposes a method for constructing a reasonable scale of end-to-end free-viewpoint video system that captures multiple view and depth data, reconstructs three-dimensional polygon models of objects, and display them on virtual 3D CG spaces. This system consists of a desktop PC and four Kinect sensors. First, multiple view plus depth data at four viewpoints are captured by Kinect sensors simultaneously. Then, the captured data are integrated to point cloud data by using camera parameters. The obtained point cloud data are sampled to volume data that consists of voxels. Since volume data that are generated from point cloud data are sparse, those data are made dense by using global optimization algorithm. Final step is to reconstruct surfaces on dense volume data by discrete marching cubes method. Since accuracy of depth maps affects to the quality of 3D polygon model, a simple inpainting method for improving depth maps is also presented.

  19. Environmental factors in multiple sclerosis: Epstein-Barr virus, vitamin D, and cigarette smoking.

    PubMed

    Wingerchuk, Dean M

    2011-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although its cause is not known, genetic and environmental factors both influence susceptibility to the disease. From the large array of environmental risk factors that have been examined over the past century, infection with Epstein-Barr virus, ultraviolet light exposure/vitamin D status, and cigarette smoking stand out because of the strength of supporting evidence. Epstein-Barr virus infection early in life appears to be necessary permissive step for disease development and probably acts in adolescence and early adulthood. Vitamin D-related mechanisms and cigarette smoking probably modify baseline disease risk and could plausibly do so at several stages of life; smoking appears to negatively affect disease course. This review summarizes current evidence for these 3 putative multiple sclerosis risk factors and early attempts to develop risk models and examine gene-environment interactions for this complex disease. PMID:21425266

  20. [Special cases of multiple sclerosis].

    PubMed

    Mendibe Bilbao, Mar

    2014-12-01

    Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions. PMID:25732948

  1. Morphology of step-pools in a wilderness headwater stream: The importance of standardizing geomorphic measurements

    NASA Astrophysics Data System (ADS)

    Nickolotsky, Aaron; Pavlowsky, Robert T.

    2007-01-01

    The morphology of step-pools and cascades reflect the geological and climatic factors affecting channels in mountain watersheds. This study uses longitudinal and cross-section surveys to describe a headwater stream in the Boston Mountains of the Ozarks Plateau region in Arkansas and develop morphological relationships for comparisons with other regions. In the Bowers Hollow Creek watershed (3.5 km 2), located within the boundaries of the Upper Buffalo Wilderness Area, step height and wavelength relationships are generally similar to those reported from other regions. Step-pool reaches were widely distributed in a discontinuous manner throughout the watershed. Average values of the sampled reaches are: reach slopes, 0.105 m/m; width, 6.10 m; crest particle sizes, 440 mm; step heights, 0.87 m; and step wavelengths, 6.62 m. The mean step steepness for the watershed was 0.13, whereas the mean length of a reach step to height ratio was 9:1. A comparison of morphological definitions found that the values of step height and steepness can vary by > 30% according to how step parameters are defined. Step height is particularly sensitive; thus, comparison of step height-based relationships from published data requires great care.

  2. Audio-visual affective expression recognition

    NASA Astrophysics Data System (ADS)

    Huang, Thomas S.; Zeng, Zhihong

    2007-11-01

    Automatic affective expression recognition has attracted more and more attention of researchers from different disciplines, which will significantly contribute to a new paradigm for human computer interaction (affect-sensitive interfaces, socially intelligent environments) and advance the research in the affect-related fields including psychology, psychiatry, and education. Multimodal information integration is a process that enables human to assess affective states robustly and flexibly. In order to understand the richness and subtleness of human emotion behavior, the computer should be able to integrate information from multiple sensors. We introduce in this paper our efforts toward machine understanding of audio-visual affective behavior, based on both deliberate and spontaneous displays. Some promising methods are presented to integrate information from both audio and visual modalities. Our experiments show the advantage of audio-visual fusion in affective expression recognition over audio-only or visual-only approaches.

  3. Assessing the Effectiveness of First Step to Success: Are Short-Term Results the First Step to Long-Term Behavioral Improvements?

    ERIC Educational Resources Information Center

    Sumi, W. Carl; Woodbridge, Michelle W.; Javitz, Harold S.; Thornton, S. Patrick; Wagner, Mary; Rouspil, Kristen; Yu, Jennifer W.; Seeley, John R.; Walker, Hill M.; Golly, Annemieke; Small, Jason W.; Feil, Edward G.; Severson, Herbert H.

    2013-01-01

    This article reports on the effectiveness of First Step to Success, a secondary-level intervention appropriate for students in early elementary school who experience moderate to severe behavior problems and are at risk for academic failure. The authors demonstrate the intervention's short-term effects on multiple behavioral and academic outcomes…

  4. Long-term outcomes in multiple gestations.

    PubMed

    Rand, Larry; Eddleman, Keith A; Stone, Joanne

    2005-06-01

    Children born from a multiple gestation are at increased risk for cerebral palsy, learning disability, and language and neurobehavioral deficits. With the increased incidence of multiple pregnancies and use of assisted reproductive technology (ART), these issues are more commonly affecting parents. Long-term outcomes are a critical part of preconceptual and early pregnancy counseling for parents faced with a multiple gestation or considering ART, and the provider should be well versed on issues surrounding zygosity, gestational age, higher-order multiples, and the effects of options such as multifetal pregnancy reduction. PMID:15922795

  5. 15 CFR 732.3 - Steps regarding the ten general prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... affecting § 732.3, see the List of CFR Sections Affected, which appears in the Finding Aids section of the... FOR USING THE EAR § 732.3 Steps regarding the ten general prohibitions. (a) Introduction. If your item or activity is subject to the scope of the EAR, you should then consider each of the ten...

  6. 15 CFR 732.3 - Steps regarding the ten general prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Note: For Federal Register citations affecting § 732.3, see the List of CFR Sections Affected, which... FOR USING THE EAR § 732.3 Steps regarding the ten general prohibitions. (a) Introduction. If your item or activity is subject to the scope of the EAR, you should then consider each of the ten...

  7. Spinal focal lesion detection in multiple myeloma using multimodal image features

    NASA Astrophysics Data System (ADS)

    Fränzle, Andrea; Hillengass, Jens; Bendl, Rolf

    2015-03-01

    Multiple myeloma is a tumor disease in the bone marrow that affects the skeleton systemically, i.e. multiple lesions can occur in different sites in the skeleton. To quantify overall tumor mass for determining degree of disease and for analysis of therapy response, volumetry of all lesions is needed. Since the large amount of lesions in one patient impedes manual segmentation of all lesions, quantification of overall tumor volume is not possible until now. Therefore development of automatic lesion detection and segmentation methods is necessary. Since focal tumors in multiple myeloma show different characteristics in different modalities (changes in bone structure in CT images, hypointensity in T1 weighted MR images and hyperintensity in T2 weighted MR images), multimodal image analysis is necessary for the detection of focal tumors. In this paper a pattern recognition approach is presented that identifies focal lesions in lumbar vertebrae based on features from T1 and T2 weighted MR images. Image voxels within bone are classified using random forests based on plain intensities and intensity value derived features (maximum, minimum, mean, median) in a 5 x 5 neighborhood around a voxel from both T1 and T2 weighted MR images. A test data sample of lesions in 8 lumbar vertebrae from 4 multiple myeloma patients can be classified at an accuracy of 95% (using a leave-one-patient-out test). The approach provides a reasonable delineation of the example lesions. This is an important step towards automatic tumor volume quantification in multiple myeloma.

  8. Reducing the graphene grain density in three steps.

    PubMed

    Hsieh, Ya-Ping; Chu, Yi-Hung; Tsai, He-Guang; Hofmann, Mario

    2016-03-11

    The production of large-scale, single crystalline graphene is a requirement for enhancing its electronic, mechanical, and chemical properties. Chemical vapor deposition (CVD) has shown the potential to grow high quality graphene but the simultaneous nucleation of many grains limits their achievable domain size. We report here that ultralow nucleation densities can be achieved through multi-step optimization of the catalyst morphology. First, annealing in a hydrogen-free environment is required to retain a surface copper oxide which decreases the nucleation density. Second, CuO was found to be the relevant copper species for this process and air oxidation of the copper foil at 200 °C maximizes its concentration. Both pre-treatment steps were found to affect the morphology of the catalyst and a direct correlation between nucleation density and surface roughness was found which indicates that the primary role of the oxidation step is the decrease in catalyst roughness. To further enhance this determining parameter, confined CVD was carried out after sample oxidation and hydrogen-free annealing. Each of these three steps reduces the grain density by approximately one order of magnitude resulting in ultralow nucleation densities of 1.23 grains/mm(2) and high quality, single-crystalline graphene grains of several millimeter sizes were grown using this method. PMID:26861850

  9. Reducing the graphene grain density in three steps

    NASA Astrophysics Data System (ADS)

    Hsieh, Ya-Ping; Chu, Yi-Hung; Tsai, He-Guang; Hofmann, Mario

    2016-03-01

    The production of large-scale, single crystalline graphene is a requirement for enhancing its electronic, mechanical, and chemical properties. Chemical vapor deposition (CVD) has shown the potential to grow high quality graphene but the simultaneous nucleation of many grains limits their achievable domain size. We report here that ultralow nucleation densities can be achieved through multi-step optimization of the catalyst morphology. First, annealing in a hydrogen-free environment is required to retain a surface copper oxide which decreases the nucleation density. Second, CuO was found to be the relevant copper species for this process and air oxidation of the copper foil at 200 °C maximizes its concentration. Both pre-treatment steps were found to affect the morphology of the catalyst and a direct correlation between nucleation density and surface roughness was found which indicates that the primary role of the oxidation step is the decrease in catalyst roughness. To further enhance this determining parameter, confined CVD was carried out after sample oxidation and hydrogen-free annealing. Each of these three steps reduces the grain density by approximately one order of magnitude resulting in ultralow nucleation densities of 1.23 grains/mm2 and high quality, single-crystalline graphene grains of several millimeter sizes were grown using this method.

  10. Recyclable Crosslinked Polymer Networks via One-Step Controlled Radical Polymerization.

    PubMed

    Jin, Kailong; Li, Lingqiao; Torkelson, John M

    2016-08-01

    A nitroxide-mediated polymerization strategy allows one-step synthesis of recyclable crosslinked polymeric materials from any monomers or polymers that contain carbon-carbon double bonds amenable to radical polymerization. The resulting materials with dynamic covalent bonds can show full property recovery after multiple melt-reprocessing recycles. This one-step strategy provides for both robust, relatively sustainable recyclability of crosslinked polymers and design of networks for advanced technologies. PMID:27206061

  11. A step-by-step protocol for assaying protein carbonylation in biological samples.

    PubMed

    Colombo, Graziano; Clerici, Marco; Garavaglia, Maria Elisa; Giustarini, Daniela; Rossi, Ranieri; Milzani, Aldo; Dalle-Donne, Isabella

    2016-04-15

    Protein carbonylation represents the most frequent and usually irreversible oxidative modification affecting proteins. This modification is chemically stable and this feature is particularly important for storage and detection of carbonylated proteins. Many biochemical and analytical methods have been developed during the last thirty years to assay protein carbonylation. The most successful method consists on protein carbonyl (PCO) derivatization with 2,4-dinitrophenylhydrazine (DNPH) and consequent spectrophotometric assay. This assay allows a global quantification of PCO content due to the ability of DNPH to react with carbonyl giving rise to an adduct able to absorb at 366 nm. Similar approaches were also developed employing chromatographic separation, in particular HPLC, and parallel detection of absorbing adducts. Subsequently, immunological techniques, such as Western immunoblot or ELISA, have been developed leading to an increase of sensitivity in protein carbonylation detection. Currently, they are widely employed to evaluate change in total protein carbonylation and eventually to highlight the specific proteins undergoing selective oxidation. In the last decade, many mass spectrometry (MS) approaches have been developed for the identification of the carbonylated proteins and the relative amino acid residues modified to carbonyl derivatives. Although these MS methods are much more focused and detailed due to their ability to identify the amino acid residues undergoing carbonylation, they still require too expensive equipments and, therefore, are limited in distribution. In this protocol paper, we summarise and comment on the most diffuse protocols that a standard laboratory can employ to assess protein carbonylation; in particular, we describe step-by-step the different protocols, adding suggestions coming from our on-bench experience. PMID:26706659

  12. Smoothing out step changes of LMP

    SciTech Connect

    Li, Fangxing

    2008-08-15

    The locational marginal pricing methodology may lead to a step change when system load grows, creating higher financial risk, especially for small and medium-sized market participants. A proposed continuous LMP method is a straightforward solution to eliminate these step changes when load grows. (author)

  13. Teachers: Recognize Important Steps to Reduce Cheating

    ERIC Educational Resources Information Center

    Supon, Viola

    2008-01-01

    Teachers must walk the steps and live the steps if reducing cheating is going to occur. Teachers begin this process by being cognizant and vigilant relative to administering means of measurement and assigning written work. This process includes skill acquisition in regards to: (1) acknowledging cheating, (2) purposeful planning, (3) electronic…

  14. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS STEPS FOR USING THE EAR § 732.1 Steps overview. (a)(1) Introduction. In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C. This part is intended to help you determine your obligations under...

  15. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS STEPS FOR USING THE EAR § 732.1 Steps overview. (a)(1) Introduction. In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C. This part is intended to help you determine your obligations under...

  16. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS STEPS FOR USING THE EAR § 732.1 Steps overview. (a)(1) Introduction. In this part, references to the EAR are references to 15 CFR chapter VII, subchapter C. This part is intended to help you determine your obligations under...

  17. 7 CFR 60.122 - Production step.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... FOR FISH AND SHELLFISH General Provisions Definitions § 60.122 Production step. Production step means in the case of: (a) (b) Farm-raised Fish and Shellfish: Hatched, raised, harvested, and processed. (c) Wild Fish and Shellfish: Harvested and processed....

  18. 7 CFR 60.122 - Production step.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... FOR FISH AND SHELLFISH General Provisions Definitions § 60.122 Production step. Production step means in the case of: (a) (b) Farm-raised Fish and Shellfish: Hatched, raised, harvested, and processed. (c) Wild Fish and Shellfish: Harvested and processed....

  19. 7 CFR 60.122 - Production step.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... FOR FISH AND SHELLFISH General Provisions Definitions § 60.122 Production step. Production step means in the case of: (a) (b) Farm-raised Fish and Shellfish: Hatched, raised, harvested, and processed. (c) Wild Fish and Shellfish: Harvested and processed....

  20. Twelve Steps to a Winning First Year

    ERIC Educational Resources Information Center

    Hodges, Karen

    2009-01-01

    This article offers 12 steps to jumpstart a new school librarian's career. Being the information specialist will be both challenging and rewarding as one undertakes a myriad of activities. These 12 steps will help a new school librarian's first year successful.

  1. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CFR chapter VII, subchapter C. This part is intended to help you determine your obligations under the..., Iran, and North Korea. For these countries, you may skip Steps 7 through 11 and go directly to Step 12..., Iran, and North Korea), prohibited activities of U.S. persons in support of proliferation of weapons...

  2. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CFR chapter VII, subchapter C. This part is intended to help you determine your obligations under the..., Iran, and North Korea. For these countries, you may skip Steps 7 through 11 and go directly to Step 12..., Iran, and North Korea), prohibited activities of U.S. persons in support of proliferation of weapons...

  3. Inception point for embankment dam stepped spillways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stepped spillways applied to embankment dams have become a common design practice with the rehabilitation of aging watershed dams, especially those experiencing a hazard classification change from low to high hazard. Previous research on stepped spillways focused on gravity dams where aerated flow ...

  4. A multiple-input multiple-output system for modeling the cardiac dynamics.

    PubMed

    Monzon, Jorge E; Picaza, Carlos Alvarez; Pisarello, Maria I

    2011-01-01

    We describe the dynamics of the cardiovascular system by finding the input-output relationships in the state space of a functional cardiac model, based on state equations and observability criteria of control theory. The unit step response of the multiple-input multiple-output system model illustrates the damping effect of the arterial wall to the pulsatility of the heart. Our results show that hypertensive patients exhibit a lower inertia of the blood flow. PMID:22254491

  5. Affective Dynamics in Psychopathology

    PubMed Central

    Trull, Timothy J.; Lane, Sean P.; Koval, Peter; Ebner-Priemer, Ulrich W.

    2016-01-01

    We discuss three varieties of affective dynamics (affective instability, emotional inertia, and emotional differentiation). In each case, we suggest how these affective dynamics should be operationalized and measured in daily life using time-intensive methods, like ecological momentary assessment or ambulatory assessment, and recommend time-sensitive analyses that take into account not only the variability but also the temporal dependency of reports. Studies that explore how these affective dynamics are associated with psychological disorders and symptoms are reviewed, and we emphasize that these affective processes are within a nexus of other components of emotion regulation.

  6. STEP-AIRSEDS System Engineering Support

    NASA Technical Reports Server (NTRS)

    Rowell, Tom; Taliaferro, Lanny

    2001-01-01

    This report summarizes and highlights the activities in support of the Space Transportation using Electrodynamic Propulsion Atmospheric Ionospheric Research Small Expendable Deployer Satellite (STEP-AIRSEDS) Project for the period of May 16, 2000 through September 28, 2001. The Alpha Technology, Inc. was tasked to provide support to the MSFC (Marshall Space Flight Center) in requirements development and in verification activities. Specifically, the Alpha Technology, Inc. task was to: (1) develop and maintain the STEP-AIRSEDS Project System Requirements Database; (2) develop and maintain the STEP-AIRSEDS requirements verification definition and planning support database; (3) perform requirements flow down analysis of STEP-AIRSEDS Project System Requirements to TMTC (The Michigan Technic Corporation) Level IV Requirements; (4) provide system engineering guidance to the Project as needed; (5) provide guidance to TMTC in preparation of Level IV Requirements; and (6) provide support to STEP-AIRSEDS meetings, reviews, and telecons as needed.

  7. Satellite Test of the Equivalence Principle (STEP)

    NASA Technical Reports Server (NTRS)

    Worden, Paul

    1994-01-01

    This grant provided support for the STEP (Satellite Test of the Equivalence Principle) program between October 1991 and September 1993. STEP, previously supported by NASA under Grant NAG8-837 'A Satellite Test of the Equivalence Principle,' was selected by the European Space Agency for a Phase A study as a candidate for ESA's next medium size mission (M2). STEP was conceived as a joint NASA/ESA mission with equal participation by both agencies. ESA's contribution to the program would be the spacecraft; NASA would provide the launcher and half of the instrument, while the other half of the instrument would be provided by various European agencies. STEP was in competition with three other programs, INTEGRAL, PRISMA, and MARSNET. The final selection of a single mission for M2 took place in April 1993. STEP was not selected for M2 but made a very close second. The program is continuing in modified form.

  8. Influence of multiple stressors on the auto-remediation processes occurring in salt marshes.

    PubMed

    Sousa, Ana I; Lillebø, Ana I; Pardal, Miguel A; Caçador, Isabel

    2011-07-01

    Due to increasing global population, salt marshes have been subjected to multiple stressors such as increasing nutrient loadings and historical contamination. In order to better understand how does the salt marsh plants auto-remediation capacity (phytoaccumulation of metals) is affected by cultural eutrophication, an experiment was performed under controlled conditions. Plants were exposure to equal metal concentrations (Zn, Cu, and Ni - micronutrients, and Cd - class B metal) simulating historical contamination and three different concentrations of nitrogen (nitrate) simulating steps of cultural eutrophication. According to our study, under the tested concentrations, cultural eutrophication does not seem to affect Zn, Cu and Ni phytoremediation of H. portulacoides, but the ecosystem service of Cd phytoremediation seems to be promoted. Nevertheless, Cd high toxicity and bioaccumulation should be taken into account, as well as the vulnerability of salt marsh ecosystems, whose reduction will have drastic consequences to the ecosystem health. PMID:21592533

  9. Stepping onto the STEM Pathway: Factors Affecting Talented Students' Declaration of STEM Majors in College

    ERIC Educational Resources Information Center

    Heilbronner, Nancy N.

    2011-01-01

    Despite a growing national need to develop capabilities in science, technology, engineering, and mathematics (STEM), many men and women who are considered talented in these areas during high school choose not to pursue STEM undergraduate majors. A purpose of the current study was to better understand factors that contribute to an individual's…

  10. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport

    PubMed Central

    Fernández-Suárez, María E.; Escolà-Gil, Joan C.; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A.; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [3H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [3H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  11. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    PubMed

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  12. Evaluation of Visual Arts Lesson Gains According to the Learning Steps of Cognitive, Affective Psychomotor Areas

    ERIC Educational Resources Information Center

    Tataroglu, Eylem

    2012-01-01

    Primary education (1-8 Grades) Visual Arts Instruction Schedule is a program built up and constituted by a commission composed of academicians and specialist teachers in their fields within the body of Ministry of National Education in year 2006 on the basis of "constructivist approach" philosophy of education. Instruction Schedule…

  13. Molecular mechanism of ERK dephosphorylation by striatal-enriched protein tyrosine phosphatase (STEP)

    PubMed Central

    Li, Hui; Li, Kang-shuai; Su, Jing; Chen, Lai-Zhong; Xu, Yun-Fei; Wang, Hong-Mei; Gong, Zheng; Cui, Guo-Ying; Yu, Xiao; Wang, Kai; Yao, Wei; Xin, Tao; Li, Min-Yong; Xiao, Kun-Hong; An, Xiao-fei; Huo, Yuqing; Xu, Zhi-gang; Sun, Jin-Peng; Pang, Qi

    2013-01-01

    Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward pNPP, phospho-tyrosine-containing peptides, and the full-length phospho-ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N-terminal regulatory region and key residues in its active site. Specifically, both KIM and KIS of STEP were required for ERK interaction. In addition to the N-terminal KIS region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho-ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho-ERK peptide sequence through its active site, and the contact of STEP F311 with phospho-ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP-ERK recognition, which could serve as a potential therapy for neurological disorders. PMID:24117863

  14. Disability in multiple sclerosis

    PubMed Central

    Chamot, Eric; Salter, Amber R.; Cutter, Gary R.; Bacon, Tamar E.; Herbert, Joseph

    2013-01-01

    Objective: To create a reference table of disability outcomes in multiple sclerosis (MS) that would enable patients to rank their disability relative to others' with similar disease duration and to develop a cost-effective research tool for comparing MS severity across patient populations and time periods. Methods: The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry collects disability data from patients with MS on a validated, 9-point Patient-Determined Disease Steps (PDDS) scale. We compiled the Disability Expectancy Table, which displays cumulative frequencies of PDDS scores for each year of disease duration, from 0 to 45 years. We also tabulated disease duration–adjusted mean ranks of PDDS scores, referred to as Patient-derived MS Severity Scores (P-MSSS). Results: The cohort consisted of 27,918 NARCOMS enrollees, 72.7% of whom were female and 90.1% of whom were white. Mean age at symptom onset was 30.1 ± 10.1 years, and age at enrollment was 47.1 ± 11.0 years. The Disability Expectancy Table and P-MSSS afford a detailed overview of disability outcomes in a large MS cohort over a 45-year period. In the first year of disease, 15% of patients reported need of ambulatory aid, and 4% needed bilateral assistance or worse; after 45 years of disease, 76% of patients required ambulatory aid, and 52% bilateral assistance or worse. Proportion of patients who reported minimal or no interference in daily activities (PDDS ≤ 1) declined from 63% in the first year to 8% after 45 years of disease. Conclusion: The Disability Expectancy Table allows individual patients to determine how their disability ranks relative to NARCOMS enrollees with the same disease duration. P-MSSS may be used to compare disability across patient populations and to track disease progression in patient cohorts. P-MSSS does not require a formal neurologic examination and may therefore find wide applicability as a practical and cost-effective outcome measure in

  15. DEVELOPMENT OF A HYDROSTATIC JOURNAL BEARING WITH SLIT-STEP COMPENSATION

    SciTech Connect

    Hale, L C; Donaldson, R R; Castro, C; Chung, C A; Hopkins, D J

    2006-07-28

    This paper describes the mathematical modeling and initial testing of an oil-hydrostatic bearing that derives compensation from both a central radial slit where fluid enters and stepped clearances near each end. Bearings using either a radial slit or stepped clearances for compensation were well studied over forty years ago by Donaldson. These bearings have smooth bores uninterrupted with multiple recesses around the circumference. The present slit-step bearing achieves the best of both types with somewhat higher hydrostatic stiffness than the slit bearing and fluid shear drag lower than the step bearing. This is apparent in TABLE 1, which compares calculated values of initial (i.e., centered) hydrostatic stiffness for each type. The slit-step bearing is one of several types being studied at Lawrence Livermore National Laboratory for possible use on the Precision Optical Grinder and Lathe (POGAL).

  16. In Australia: Multiple Intelligences in Multiple Settings.

    ERIC Educational Resources Information Center

    Vialle, Wilma

    1997-01-01

    In Australia, Gardner's multiple-intelligences theory has strongly influenced primary, preschool, and special education. A survey of 30 schools revealed that teachers use two basic approaches: teaching to, and teaching through, multiple intelligences. The first approach might develop children's music skills via playing an instrument. The second…

  17. Diffusion of tungsten on stepped tungsten surfaces

    NASA Astrophysics Data System (ADS)

    Choi, D. S.; Kim, S. K.; Gomer, R.

    1990-08-01

    Self-diffusion of thermally generated tungsten atoms near (123) and (257), on the zone (011)-(112) and on (023), on the zone (011)-(001) of a tungsten field emitter has been investigated by the field-emission fluctuation method, using a rectangular probe in order to investigate diffusion anisotropy. In agreement with earlier findings of Gong and Gomer [J. Chem. Phys. 88 (1988) 1359, 1370] diffusion of single W atoms along and across (011) terraces separated by (011) steps, i.e. step edges running along [111] is essentially isotropic with Ed = 16 kcal, D0 ≈ 10 -4 cm 2 s -1, while atoms can cross (001) oriented steps only with much activation energy: Ed ≈ 35 kcal, D0 = 10 -2 cm -2 s -1. Slow diffusion parallel to steps attributed previously by Gong Chem. Phys. 88 (1988) 1359, 1370] to kink motion was also seen along the zone (011)-(112) but seems more complicated than previously assumed, with several regimes, which may correspond to motions of different kink configurations. Distinct dips in the slow regime diffusion coefficients occurred at 910 K, somewhat higher than the previously seen onset of dips, 875 K, and may indicate roughening, as previously hypothesized. Slow diffusion perpendicular to steps was also seen in this zone and is not fully understood. It may arise from some step components always perpendicular to the short slit dimensions, or may correspond to more complicated surface configurations than the step and terrace pattern on an ideal emitter surface.

  18. One-step reconstruction of assembled 3D holographic scenes

    NASA Astrophysics Data System (ADS)

    Velez Zea, Alejandro; Barrera-Ramírez, John Fredy; Torroba, Roberto

    2015-12-01

    We present a new experimental approach for reconstructing in one step 3D scenes otherwise not feasible in a single snapshot from standard off-axis digital hologram architecture, due to a lack of illuminating resources or a limited setup size. Consequently, whenever a scene could not be wholly illuminated or the size of the scene surpasses the available setup disposition, this protocol can be implemented to solve these issues. We need neither to alter the original setup in every step nor to cover the whole scene by the illuminating source, thus saving resources. With this technique we multiplex the processed holograms of actual diffuse objects composing a scene using a two-beam off-axis holographic setup in a Fresnel approach. By registering individually the holograms of several objects and applying a spatial filtering technique, the filtered Fresnel holograms can then be added to produce a compound hologram. The simultaneous reconstruction of all objects is performed in one step using the same recovering procedure employed for single holograms. Using this technique, we were able to reconstruct, for the first time to our knowledge, a scene by multiplexing off-axis holograms of the 3D objects without cross talk. This technique is important for quantitative visualization of optically packaged multiple images and is useful for a wide range of applications. We present experimental results to support the method.

  19. Analogue step-by-step DC component eliminator for 24-hour PPG signal monitoring.

    PubMed

    Pilt, Kristjan; Meigas, Kalju; Lass, Jaanus; Rosmann, Mart; Kaik, Jüri

    2007-01-01

    For applications where PPG signal AC component needs to be measured without disturbances in its shape and recorded digitally with high digitalization accuracy, the step-by-step DC component eliminator is developed. This paper describes step-by-step DC component eliminator, which is utilized with analogue comparator and operational amplifier. It allows to record PPG signal without disturbances in its shape in 24-hours PPG signal monitoring system. The experiments with PPG signal have been carried out. PMID:18002130

  20. Recognition of Ramps and Steps by People with Low Vision

    PubMed Central

    Bochsler, Tiana M.; Legge, Gordon E.; Gage, Rachel; Kallie, Christopher S.

    2013-01-01

    Purpose. Detection and recognition of ramps and steps are important for the safe mobility of people with low vision. Our primary goal was to assess the impact of viewing conditions and environmental factors on the recognition of these targets by people with low vision. A secondary goal was to determine if results from our previous studies of normally sighted subjects, wearing acuity-reducing goggles, would generalize to low vision. Methods. Sixteen subjects with heterogeneous forms of low vision participated—acuities from approximately 20/200 to 20/2000. They viewed a sidewalk interrupted by one of five targets: a single step up or down, a ramp up or down, or a flat continuation of the sidewalk. Subjects reported which of the five targets was shown, and percent correct was computed. The effects of viewing distance, target–background contrast, lighting arrangement, and subject locomotion were investigated. Performance was compared with a group of normally sighted subjects who viewed the targets through acuity-reducing goggles. Results. Recognition performance was significantly better at shorter distances and after locomotion (compared with purely stationary viewing). The effects of lighting arrangement and target–background contrast were weaker than hypothesized. Visibility of the targets varied, with the step up being more visible than the step down. Conclusions. The empirical results provide insight into factors affecting the visibility of ramps and steps for people with low vision. The effects of distance, target type, and locomotion were qualitatively similar for low vision and normal vision with artificial acuity reduction. However, the effects of lighting arrangement and background contrast were only significant for subjects with normal vision. PMID:23221068

  1. Phonon scattering in graphene over substrate steps

    SciTech Connect

    Sevinçli, H.; Brandbyge, M.

    2014-10-13

    We calculate the effect on phonon transport of substrate-induced bends in graphene. We consider bending induced by an abrupt kink in the substrate, and provide results for different step-heights and substrate interaction strengths. We find that individual substrate steps reduce thermal conductance in the range between 5% and 47%. We also consider the transmission across linear kinks formed by adsorption of atomic hydrogen at the bends and find that individual kinks suppress thermal conduction substantially, especially at high temperatures. Our analysis show that substrate irregularities can be detrimental for thermal conduction even for small step heights.

  2. Step-by-Step Solution Possibilities in Different Computer Algebra Systems.

    ERIC Educational Resources Information Center

    Tonisson, Eno

    This paper compares a number of different Computer Algebra Systems (CAS) in their solution of one-step and multi-step problems. The CAS programs considered include DERIVE, Maple, Mathematica, and MuPAD while the problems are taken from the final examinations of grades 9 and 12 in Estonian schools. The different outputs to one-step problems with…

  3. Macintosh Step by Step: Footsteps To Follow for Learning To Use the Macintosh Computer.

    ERIC Educational Resources Information Center

    Piazza, David J.

    This step by step introductory guide, which is divided into a series of 58 topics that should be familiar to any user of the Macintosh, is intended to aid new users in learning the topics that they will need to know to be successful with the Macintosh. Each topic includes the following: (1) a numbered set of sequential steps to be followed,…

  4. First Steps PLUS: Yakima First Steps Mobilization Project for Pregnant Substance Abusers. An Interim Evaluation Report.

    ERIC Educational Resources Information Center

    Nordlund, Daniel J.; And Others

    The Yakima First Steps Mobilization Project for Pregnant Substance Abusers, known as First Steps PLUS, is a demonstration project. The project seeks to improve the health outcomes of pregnant substance abusing women and their infants by enhancing existing perinatal services provided through Washington's First Steps Maternity Care Program and by…

  5. Effect of Simplified One-Step Drilling Protocol on Osseointegration.

    PubMed

    Patel, Arpita; Gil, Luiz F; Castellano, Arthur; Freitas, Gileade; Navarro, Daniel; Peredo, Ana P; Tovar, Nick; Coelho, Paulo

    2016-01-01

    This study was designed to compare the combined effect of two different drilling techniques (conventional expansion and one-step) and four different implant geometries in a beagle dog model. The nondecalcified bone-implant samples underwent histologic/metric analysis at 2 and 6 weeks. Morphologic analysis showed similarities between different drilling technique groups and implant geometries. Histomorphometric parameters, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) were analyzed, and no statistical difference between drilling groups and/or implant geometry was found. Time was the only variable that affected BIC and BAFO, suggesting that the two protocols are equally biocompatible and osseoconductive. PMID:27560682

  6. A multiple-objective optimal exploration strategy

    USGS Publications Warehouse

    Christakos, G.; Olea, R.A.

    1988-01-01

    Exploration for natural resources is accomplished through partial sampling of extensive domains. Such imperfect knowledge is subject to sampling error. Complex systems of equations resulting from modelling based on the theory of correlated random fields are reduced to simple analytical expressions providing global indices of estimation variance. The indices are utilized by multiple objective decision criteria to find the best sampling strategies. The approach is not limited by geometric nature of the sampling, covers a wide range in spatial continuity and leads to a step-by-step procedure. ?? 1988.

  7. Variable grid-size and time-step finite difference method for seismic forward modeling and reverse-time migration

    NASA Astrophysics Data System (ADS)

    Wang, Yue

    A new variable grid-size and time-step finite-difference (FD) method is developed and applied to three different geophysical problems: simulation of tube waves in boreholes, three-dimensional (3-D) ground-motion simulation in sedimentary basin models, and reverse-time migration of multicomponent data. Unlike the conventional FD method, which uses a fixed grid-size and time-step for the entire model region, spatially variable grid-sizes and time-steps are used to achieve the optimal computational efficiency. For tube wave simulations, a fine grid-spacing is used for simulation inside the borehole region, while a coarse grid is used in the exterior region. While the stability condition requires a very fine time step for the fine grid, a variable time-step method provides coarse time steps for simulation in the coarse grid. Variable grid-size and time-step changes are used to achieve both accuracy and efficiency in the simulations. Numerical tests are performed for the Bayou Choctaw salt-flank model with different borehole models. The results show the important borehole effects on the seismic wavefield for a realistic source bandwidth. The combination of variable grid-size and time-step methods reduces computational costs by several orders of magnitude for the borehole models. Viscoelastic 3-D simulations are performed for a three-layer Salt Lake basin model. The near-surface unconsolidated layer is modeled with a fine grid, and the deep part of the model is modeled by a coarse grid. Simulation results show that the 3-D basin features and the shallow layer significantly affect the amplitude and duration time of the ground motion. In the elastic case, the approximation by 2-D modeling is insufficient to simulate the 3-D ground motion response. A basin model without a shallow low-velocity layer underestimates the ground motion duration and cumulative kinetic energy by 50% or more. The simulation of a Bingham Mine blast suggests that a lower S-velocity should be used to

  8. Partial oxidation of step-bound water leads to anomalous pH effects on metal electrode step-edges.

    PubMed

    Schwarz, Kathleen; Xu, Bingjun; Yan, Yushan; Sundararaman, Ravishankar

    2016-06-28

    The design of better heterogeneous catalysts for applications such as fuel cells and electrolyzers requires a mechanistic understanding of electrocatalytic reactions and the dependence of their activity on operating conditions such as pH. A satisfactory explanation for the unexpected pH dependence of electrochemical properties of platinum surfaces has so far remained elusive, with previous explanations resorting to complex co-adsorption of multiple species and resulting in limited predictive power. This knowledge gap suggests that the fundamental properties of these catalysts are not yet understood, limiting systematic improvement. Here, we analyze the change in charge and free energies upon adsorption using density-functional theory (DFT) to establish that water adsorbs on platinum step edges across a wide voltage range, including the double-layer region, with a loss of approximately 0.2 electrons upon adsorption. We show how this as-yet unreported change in net surface charge due to this water explains the anomalous pH variations of the hydrogen underpotential deposition (Hupd) and the potentials of zero total charge (PZTC) observed in published experimental data. This partial oxidation of water is not limited to platinum metal step edges, and we report the charge of the water on metal step edges of commonly used catalytic metals, including copper, silver, iridium, and palladium, illustrating that this partial oxidation of water broadly influences the reactivity of metal electrodes. PMID:27250359

  9. Take Steps to Prevent Type 2 Diabetes

    MedlinePlus

    ... I at Risk? 4 of 9 sections Take Action! Take Action: Talk to Your Doctor Take these steps to ... Previous section Signs 5 of 9 sections Take Action: Cost and Insurance What about cost? Thanks to ...

  10. "GIANT" Steps to Create Online Orientations

    ERIC Educational Resources Information Center

    Bacon, Pamela

    2005-01-01

    Online orientation is provided due to the flexibility of online learning. The online orientation consists of the GIANT steps which stands for Get support, Identify your curriculum, Assemble your program, Navigate students through the pilot project and Test students.

  11. Reducing Stepping-Motor Power Consumption

    NASA Technical Reports Server (NTRS)

    Williams, C. J.

    1985-01-01

    Direct-current stepping motors used in computer peripherals, process control, and precision remote-positioning equipment constantly dissipate power and create heat even when not moving. Circuit design energizes stepper motor only when pulses are present on control input.

  12. Five Steps to Safer Health Care

    MedlinePlus

    ... to Safer Health Care Five Steps to Safer Health Care: Patient Fact Sheet This information is for reference ... safety is one of the Nation's most pressing health care challenges. A 1999 report by the Institute of ...

  13. Seven Steps to Sustainable Change at WPI.

    ERIC Educational Resources Information Center

    Grogan, William R.; Vaz, Richard

    2003-01-01

    Describes the seven steps over a course of several years, which enabled Worcester Polytechnic Institute to implement and sustain a reconstruction of undergraduate education to involve no set curriculum, but rather three qualifying projects. (EV)

  14. Quit Smoking: 5 Steps to START

    MedlinePlus

    ... Smoking" Articles You Can Quit Smoking: Here's How / 5 Steps to START / Keep Trying! / Secondhand Smoke/"Light" Tobacco/Smokeless Tobacco / 3 Tools to Help You Quit / Latest NIH Research Winter ...

  15. Next Steps for Credit Availability Act

    THOMAS, 112th Congress

    Rep. Velazquez, Nydia M. [D-NY-12

    2012-06-08

    07/11/2012 Referred to the Subcommittee on Capital Markets and Government Sponsored Enterprises. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  16. Next Steps for Credit Availability Act

    THOMAS, 113th Congress

    Rep. Velazquez, Nydia M. [D-NY-12

    2013-01-03

    10/23/2013 Hearings Held by the Subcommittee on Capital Markets and Government Sponsored Enterprises Prior to Referral. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  17. Four Practical Steps to Buying Copiers.

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    1999-01-01

    Presents practical steps for avoiding overbuying when selecting copiers for university administration. Evaluating copying needs, eliminating excessive features, examining the dealer's capabilities, and being patient for the right price are discussed. (GR)

  18. Take Steps to Prevent Type 2 Diabetes

    MedlinePlus

    ... En español Take Steps to Prevent Type 2 Diabetes Browse Sections The Basics Overview Types of Diabetes ... 1 of 9 sections The Basics: Types of Diabetes What is diabetes? Diabetes is a disease. People ...

  19. [Pathophysiology of multiple sclerosis].

    PubMed

    Smith, Kenneth J

    2006-06-30

    Patients with multiple sclerosis (MS) can exhibit an exceptionally wide variety of symptoms. This is largely due to the semi-random distribution of the lesions in the central nervous system (CNS). Most lesions occur in apparently "silent" areas in the brain, and so cause no detectable symptoms. The disease is therefore much more active than a mere clinical monitoring would suggest. Most symptoms are related to a loss of function. During the relapses, this is due to a failure of axonal conduction at the site of the lesion(s). The conduction block is caused by the local demyelination which prevents the saltatory conduction but also seemingly, to some extend, by the inflammation per se. Remissions are related to a recovery of function of the affected axons owing to a spreading of sodium channels along the demyelinated axolemma but also to cerebral functional plasticity and remyelination. However, nerve conduction remains slower and less secure than normal, easily altered by physico-chemical changes such as the increase in body temperature (Uhthoff's phenomenon). Remission is incomplete when the lesion has led to axonal transaction and therefore axonal loss. Progression in MS is mainly related to "slow-burning" diffuse and chronic axonal loss in a toxic inflammatory milieu. Lastly, some symptoms in MS are so-called "positive" arising from an acquired hyperexcitability of demyelinated axons and occur either spontaneously (e.g. paresthesias) or mechanically (e.g. Lhermitte's sign). PMID:16948217

  20. Projected-Fringe, Phase-Stepping Profilometer

    NASA Technical Reports Server (NTRS)

    Mercer, Carolyn; Beheim, Glenn

    1992-01-01

    Projected-fringe, phase-stepping profilometer is system of optical, electronic, optoelectronic, and electro-optical equipment measuring surface profiles of objects. Projects optical interference pattern onto object and steps phase of pattern to extract phases of interfering beams where they intersect object. Data obtained within seconds. Noncontact, full-field surface profilometer has applications, including inspection of machined and ceramic parts, printed circuit boards, and optical components. Rugged and compact, measures surfaces with variety of sizes and finishes.