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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

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

    2015-07-13

    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.

  2. 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

  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. 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.

  5. Food intake and fuel deposition in a migratory bird is affected by multiple as well as single-step changes in the magnetic field.

    PubMed

    Henshaw, Ian; Fransson, Thord; Jakobsson, Sven; Lind, Johan; Vallin, Adrian; Kullberg, Cecilia

    2008-03-01

    Recent studies have shown that migratory thrush nightingales (Luscinia luscinia) experimentally treated with multiple changes of the magnetic field simulating a journey to their target stopover area in northern Egypt, increased fuel deposition as expected in preparation to cross the Sahara desert. To investigate the significance of food intake on the body mass changes observed, in the work described here we analysed food intake of the nightingales under study in those earlier experiments. Furthermore, to study whether a single change in the magnetic field directly to northern Egypt is sufficient to provide information for fuelling decisions, we performed a new experiment, exposing thrush nightingales trapped in Sweden, directly to a magnetic field of northern Egypt. Our results show that an experimentally induced magnetic field of northern Egypt, close to the barrier crossing, triggers the same response in fuel deposition as experiments with multiple changes of the magnetic field simulating a migratory journey from Sweden to Egypt, suggesting that migratory birds do not require successive changes in field parameters to incorporate magnetic information into their migratory program. Furthermore, irrespective of experimental set up (single or multiple changes of the magnetic field parameters) increase in food intake seems to be the major reason for the observed increase in fuelling rate compared with control birds, suggesting that geomagnetic information might trigger hormonal changes in migratory birds enabling appropriate fuelling behaviour during migration.

  6. 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…

  7. 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.

  8. 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

  9. Dynamical multiple-time stepping methods for overcoming resonance instabilities.

    PubMed

    Chin, Siu A

    2004-01-01

    Current molecular dynamics simulations of biomolecules using multiple time steps to update the slowly changing force are hampered by instabilities beginning at time steps near the half period of the fastest vibrating mode. These "resonance" instabilities have became a critical barrier preventing the long time simulation of biomolecular dynamics. Attempts to tame these instabilities by altering the slowly changing force and efforts to damp them out by Langevin dynamics do not address the fundamental cause of these instabilities. In this work, we trace the instability to the nonanalytic character of the underlying spectrum and show that a correct splitting of the Hamiltonian, which renders the spectrum analytic, restores stability. The resulting Hamiltonian dictates that in addition to updating the momentum due to the slowly changing force, one must also update the position with a modified mass. Thus multiple-time stepping must be done dynamically.

  10. 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

  11. 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.

  12. The Effects of Multiple-Step and Single-Step Directions on Fourth and Fifth Grade Students' Grammar Assessment Performance

    ERIC Educational Resources Information Center

    Mazerik, Matthew B.

    2006-01-01

    The mean scores of English Language Learners (ELL) and English Only (EO) students in 4th and 5th grade (N = 110), across the teacher-administered Grammar Skills Test, were examined for differences in participants' scores on assessments containing single-step directions and assessments containing multiple-step directions. The results indicated no…

  13. Step-by-step description of a computationally efficient version of multiple hypothesis tracking

    NASA Astrophysics Data System (ADS)

    Werthmann, John R.

    1992-08-01

    Under the recently completed Covert Air Combat Definition Study, a form of multiple hypothesis tracking, known as structured branching (SB/MHT), was developed and tested by Hughes Radar Systems Group. SB/MHT offers significant computational savings compared to other approaches, enabling it to maintain a great number of hypothesized tracks, initiated in high false alarm environments without overwhelming current generation tactical processors. Under the recently initiated Advanced Tracking Algorithms Program, the SB/MHT algorithm will be further developed and hosted on a tactical airborne processor to demonstrate realtime performance. This paper walks through the algorithm sequence of operations in order to give the reader an intuitive understanding of SB/MHT. The paper begins with a description of the basic idea of MHT algorithms; i.e., to carry hypotheses when there is doubt about which tracks to associate with new observations. The primary differences between SB/MHT and `classical' MHT are briefly discussed. Each operation in the SB/MHT block diagram is explained by stepping through the operations that would take place given an assumed set of tracks, and a set of observations to be processed. Operations to be discussed include: observation filtering and prediction, gate formation and observation-to-track association, track branching and initiation, initial track scoring and pruning, track clustering, hypothesis generation and scoring, and finally, global track scoring and pruning. Methods for controlling track-file growth and its resultant computational load are also discussed. Although high level in terms of the amount of detail covered, this description should provide the reader with a good understanding of the fundamental characteristics of a streamlined MHT algorithm envisioned to operate in real time on a current generation airborne tactical processor.

  14. [Affective and psychotic disorders in multiple sclerosis].

    PubMed

    Pozuelo-Moyano, Beatriz; Benito-León, Julián

    2015-12-01

    Introduccion. La esclerosis multiple (EM) es la segunda causa mas importante de discapacidad de origen neurologico en los adultos jovenes. Tanto la sintomatologia fisica como la psiquiatrica (trastornos afectivos y psicoticos) impactan de manera negativa en la calidad de vida relacionada con la salud de los pacientes con EM. Objetivo. Elucidar de modo critico la prevalencia y la patogenia de los sintomas afectivos y psicoticos presentes en la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados mas significativos que han analizado la prevalencia y la patogenia de la sintomatologia afectiva y psicotica en los pacientes con EM. Para explorar la asociacion entre los sintomas afectivos y psicoticos con la EM se ha revisado la evidencia disponible hasta el momento. Conclusiones. La depresion es el trastorno psiquiatrico mas frecuente en la EM. Es necesaria mas investigacion para elucidar los mecanismos subyacentes que pueden provocar sintomas afectivos y psicoticos en la EM. El control de dichos sintomas en los pacientes de EM podria mejorar su calidad de vida relacionada con la salud.

  15. A multiple step random walk Monte Carlo method for heat conduction involving distributed heat sources

    NASA Astrophysics Data System (ADS)

    Naraghi, M. H. N.; Chung, B. T. F.

    1982-06-01

    A multiple step fixed random walk Monte Carlo method for solving heat conduction in solids with distributed internal heat sources is developed. In this method, the probability that a walker reaches a point a few steps away is calculated analytically and is stored in the computer. Instead of moving to the immediate neighboring point the walker is allowed to jump several steps further. The present multiple step random walk technique can be applied to both conventional Monte Carlo and the Exodus methods. Numerical results indicate that the present method compares well with finite difference solutions while the computation speed is much faster than that of single step Exodus and conventional Monte Carlo methods.

  16. 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.

  17. 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

  18. Multiple-step terminal control with parameter identification and prediction during flight vehicle descent

    NASA Astrophysics Data System (ADS)

    Sirazetdinov, T. K.; Kiselev, V. I.

    A method is presented for multiple-step terminal control at a section of the glide path of a flight vehcile in the dense layers of the atmosphere. In accordance with the method, the parameters are identified and predicted at each step of the control process. Results of a computer simulation of the motion of a flight vehicle are presented.

  19. 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…

  20. Copackaging of multiple adeno-associated viral vectors in a single production step.

    PubMed

    Doerfler, Phillip A; Byrne, Barry J; Clément, Nathalie

    2014-10-01

    Limiting factors in large preclinical and clinical studies utilizing adeno-associated virus (AAV) for gene therapy are focused on the restrictive packaging capacity, the overall yields, and the versatility of the production methods for single AAV vector production. Furthermore, applications where multiple vectors are needed to provide long expression cassettes, whether because of long cDNA sequences or the need of different regulatory elements, require that each vector be packaged and characterized separately, directly affecting labor and cost associated with such manufacturing strategies. To overcome these limitations, we propose a novel method of vector production that allows for the packaging of multiple expression cassettes in a single transfection step. Here we combined two expression cassettes in predetermined ratios before transfection and empirically demonstrate that the output vector recapitulates the predicted ratios. Titration by quantitative polymerase chain reaction of AAV vector genome copies using shared or unique genetic elements allowed for delineation of the individual vector contribution to the total preparation that showed the predicted differential packaging outcomes. By copackaging green fluorescent protein (GFP) and mCherry constructs, we demonstrate that both vector genome and infectious titers reiterated the ratios utilized to produce the constructs by transfection. Copackaged therapeutic constructs that only differ in transcriptional elements produced a heterogeneous vector population of both constructs in the predefined ratios. This study shows feasibility and reproducibility of a method that allows for two constructs, differing in either transgene or transcription elements, to be efficiently copackaged and characterized simultaneously, reducing cost of manufacturing and release testing.

  1. Knee osteoarthritis negatively affects the recovery step following large forward-directed postural perturbations.

    PubMed

    Pater, Mackenzie L; Rosenblatt, Noah J; Grabiner, Mark D

    2016-05-01

    The reasons for higher fall risk of people with osteoarthritis (OA) compared to people without OA are not known. It is possible that following a loss of balance OA may negatively affect the recovery stepping response. Stepping responses have not been reported for people with knee OA. Here, we compared recovery step kinematics following laboratory-induced trip and following a large treadmill-delivered perturbation simulating a trip between a group of women with and without self-reported knee OA. We hypothesized that knee OA would significantly impair recovery step kinematics compared to those of a control group. Following the laboratory-induced trip, step length and trunk flexion velocity at recovery step completion of women with OA were significantly impaired and more so for the women who fell. Following the treadmill-delivered perturbation, the recovery step kinematics of women with OA were not significantly impaired. For both perturbations, the women who fell had significantly impaired recovery step kinematics compared to those who did not fall, regardless of OA. The results are consistent with previous work on healthy middle aged and older women and suggest that the same biomechanical risk factors for trip-related falls are shared by middle age and older women regardless of the presence of knee OA. The results support the need to determine whether training protocols which have been shown to improve recovery step kinematics and reduce prospective falls by healthy older women can have similar outcomes for people with knee OA.

  2. 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...

  3. 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.

  4. 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

  5. Speckle evolution with multiple steps of least-squares phase removal

    SciTech Connect

    Chen Mingzhou; Dainty, Chris; Roux, Filippus S.

    2011-08-15

    We study numerically the evolution of speckle fields due to the annihilation of optical vortices after the least-squares phase has been removed. A process with multiple steps of least-squares phase removal is carried out to minimize both vortex density and scintillation index. Statistical results show that almost all the optical vortices can be removed from a speckle field, which finally decays into a quasiplane wave after such an iterative process.

  6. 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

  7. 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

  8. 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

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

    PubMed

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

    2002-06-01

    In developing murine growth plates, chondrocytes near the articular surface (periarticular chondrocytes) proliferate, differentiate into flat column-forming proliferating cells (columnar chondrocytes), stop dividing and finally differentiate into hypertrophic cells. Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophic cells, stimulates expression of parathyroid hormone (PTH)-related peptide (PTHrP) which negatively regulates terminal chondrocyte differentiation through the PTH/PTHrP receptor (PPR). However, the roles of PTHrP and Ihh in regulating earlier steps in chondrocyte differentiation are unclear. We present novel mouse models with PPR abnormalities that help clarify these roles. In mice with chondrocyte-specific PPR ablation and mice with reduced PPR expression, chondrocyte differentiation was accelerated not only at the terminal step but also at an earlier step: periarticular to columnar differentiation. In these models, upregulation of Ihh action in the periarticular region was also observed. In the third model in which the PPR was disrupted in about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes was upregulated because of ectopically differentiated hypertrophic chondrocytes that had lost PPR. Acceleration of periarticular to columnar differentiation was also noted in this mouse, while most of periarticular chondrocytes retained PPR signaling. These data suggest that Ihh positively controls differentiation of periarticular chondrocytes independently of PTHrP. Thus, chondrocyte differentiation is controlled at multiple steps by PTHrP and Ihh through the mutual regulation of their activities. PMID:12050144

  10. High-transmittance subwavelength metal grating with relief structure composed of multiple steps.

    PubMed

    Wang, Zhongfei; Zhang, Dawei; Wang, Qi; Xu, Banglian; Tang, Qingyong; Huang, Yuanshen; Zhuang, Songlin

    2014-01-01

    A new kind of subwavelength metal grating with relief structure is designed and analyzed, in which the shape of the grating lines is no longer a single rectangle, but a relief structure with multiple steps. GsolverV52 was used to determine the optimal values of the grating period, groove depth, and the number of steps. The optical performance of the novel structure is evaluated and compared in terms of the transmission efficiency and extinction ratio over the visible and near-infrared wavelength spectrum. It is shown that, in the near-infrared band, the maximum transmittance can be increased about 15% compared to the traditional metal grating under the same parameters. With the unique characteristics, the metal grating is expected to find applications in liquid crystal display fields, polarization imaging, optical communication, and so on. PMID:24701172

  11. MAX2 affects multiple hormones to promote photomorphogenesis.

    PubMed

    Shen, Hui; Zhu, Ling; Bu, Qing-Yun; Huq, Enamul

    2012-05-01

    Ubiquitin-26S proteasome system (UPS) has been shown to play central roles in light and hormone-regulated plant growth and development. Previously, we have shown that MAX2, an F-box protein, positively regulates facets of photomorphogenic development in response to light. However, how MAX2 controls these responses is still unknown. Here, we show that MAX2 oppositely regulates GA and ABA biosynthesis to optimize seed germination in response to light. Dose-response curves showed that max2 seeds are hyposensitive to GA and hypersensitive to ABA in seed germination responses. RT-PCR assays demonstrated that the expression of GA biosynthetic genes is down-regulated, while the expression of GA catabolic genes is up-regulated in the max2 seeds compared to wild-type. Interestingly, expression of both ABA biosynthetic and catabolic genes is up-regulated in the max2 seeds compared to wild-type. Treatment with an auxin transport inhibitor, NPA, showed that increased auxin transport in max2 seedlings contributes to the long hypocotyl phenotype under light. Moreover, light-signaling phenotypes are restricted to max2, as the biosynthetic mutants in the strigolactone pathway, max1, max3, and max4, did not display any defects in seed germination and seedling de-etiolation compared to wild-type. Taken together, these data suggest that MAX2 modulates multiple hormone pathways to affect photomorphogenesis.

  12. Optimized particle-mesh Ewald/multiple-time step integration for molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Batcho, Paul F.; Case, David A.; Schlick, Tamar

    2001-09-01

    We develop an efficient multiple time step (MTS) force splitting scheme for biological applications in the AMBER program in the context of the particle-mesh Ewald (PME) algorithm. Our method applies a symmetric Trotter factorization of the Liouville operator based on the position-Verlet scheme to Newtonian and Langevin dynamics. Following a brief review of the MTS and PME algorithms, we discuss performance speedup and the force balancing involved to maximize accuracy, maintain long-time stability, and accelerate computational times. Compared to prior MTS efforts in the context of the AMBER program, advances are possible by optimizing PME parameters for MTS applications and by using the position-Verlet, rather than velocity-Verlet, scheme for the inner loop. Moreover, ideas from the Langevin/MTS algorithm LN are applied to Newtonian formulations here. The algorithm's performance is optimized and tested on water, solvated DNA, and solvated protein systems. We find CPU speedup ratios of over 3 for Newtonian formulations when compared to a 1 fs single-step Verlet algorithm using outer time steps of 6 fs in a three-class splitting scheme; accurate conservation of energies is demonstrated over simulations of length several hundred ps. With modest Langevin forces, we obtain stable trajectories for outer time steps up to 12 fs and corresponding speedup ratios approaching 5. We end by suggesting that modified Ewald formulations, using tailored alternatives to the Gaussian screening functions for the Coulombic terms, may allow larger time steps and thus further speedups for both Newtonian and Langevin protocols; such developments are reported separately.

  13. Correction of Footdrop Due to Multiple Sclerosis Using the STIMuSTEP Implanted Dropped Foot Stimulator

    PubMed Central

    Wilkinson Hart, Ingrid A.; Khan, Mansoor S.; Slade-Sharman, Diana E.M.

    2016-01-01

    Background: Footdrop is a significant problem in multiple sclerosis, reducing the safety and efficiency of walking. Functional electrical stimulation (FES) can produce dorsiflexion, correcting footdrop. The purpose of this retrospective analysis of clinical study data was to compare the effect of external and implanted FES devices for the correction of footdrop. Methods: External FES was used for a minimum of 6 months before implantation. Walking performance was assessed using 10-m walking speed, 3-minute walking distance, the Physiological Cost Index, and health- and device-related quality of life and device-use questionnaires. Assessments were made before implantation and a mean (SD) of 128 (24) days after surgery, with additional walking speed measurements at 3 years. Results: Twenty-three people with multiple sclerosis received the STIMuSTEP implant. Both devices enabled statistically significant increases in walking speed and walking distance, with a strong trend toward a reduced Physiological Cost Index, indicating that walking required less effort (P = .07). Both devices improved device-related quality of life. Walking speed gain with FES was maintained at 3 years. Three implants failed after falls, and there was one case of neuropraxia. The implant was used more days per week and was quicker to put on each day than the external FES device. Conclusions: The STIMuSTEP implanted dropped foot stimulator is an effective long-term intervention for the correction of footdrop. PMID:27803639

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. [Step-back method for intracanal preparation with multiple length determination of the tooth root canal].

    PubMed

    Tamarut, T; Blasković, V; Cindrić, N; Maricić, B

    1989-01-01

    A procedure of intracanal preparation of a cuneiform with cervical extension using a step-back technique is described. The length of the root canal is determined by multiple electric measurement. First, the initial measurement of the canal length (I1) is performed. The measured length is then transferred to the initial extender (No. 15), whereafter extirpation of the pulp and removal of circumpulpal dentin begin. Then the extender NO. 20 is reduced by 1 mm, and the extender No. 25 by 2 mm. When the canal have been narrowed and bent, further extenders are used to additionally reduce the working length by 1 mm more. When the pulp has been extirpated, the second canal length measurement (12) is performed, then starting to form the canal. In phase 1, the apical third from the initial (IAF) to the leading file (MAF) is treated and the cervical extension of the canal prepared by a bur drill. In further instrumentation, each next file is reduced by 1 mm of the measured canal length (12), thus shaping the canal by filling, using a step-back method. Files according to Hedström should be used thereby. Shaping of the canal is completed by a file by four numbers greater than the leading (MAF) one.

  19. Loop-loop interactions govern multiple steps in indole-3-glycerol phosphate synthase catalysis.

    PubMed

    Zaccardi, Margot J; O'Rourke, Kathleen F; Yezdimer, Eric M; Loggia, Laura J; Woldt, Svenja; Boehr, David D

    2014-03-01

    Substrate binding, product release, and likely chemical catalysis in the tryptophan biosynthetic enzyme indole-3-glycerol phosphate synthase (IGPS) are dependent on the structural dynamics of the β1α1 active-site loop. Statistical coupling analysis and molecular dynamic simulations had previously indicated that covarying residues in the β1α1 and β2α2 loops, corresponding to Arg54 and Asn90, respectively, in the Sulfolobus sulfataricus enzyme (ssIGPS), are likely important for coordinating functional motions of these loops. To test this hypothesis, we characterized site mutants at these positions for changes in catalytic function, protein stability and structural dynamics for the thermophilic ssIGPS enzyme. Although there were only modest changes in the overall steady-state kinetic parameters, solvent viscosity and solvent deuterium kinetic isotope effects indicated that these amino acid substitutions change the identity of the rate-determining step across multiple temperatures. Surprisingly, the N90A substitution had a dramatic effect on the general acid/base catalysis of the dehydration step, as indicated by the loss of the descending limb in the pH rate profile, which we had previously assigned to Lys53 on the β1α1 loop. These changes in enzyme function are accompanied with a quenching of ps-ns and µs-ms timescale motions in the β1α1 loop as measured by nuclear magnetic resonance studies. Altogether, our studies provide structural, dynamic and functional rationales for the coevolution of residues on the β1α1 and β2α2 loops, and highlight the multiple roles that the β1α1 loop plays in IGPS catalysis. Thus, substitution of covarying residues in the active-site β1α1 and β2α2 loops of indole-3-glycerol phosphate synthase results in functional, structural, and dynamic changes, highlighting the multiple roles that the β1α1 loop plays in enzyme catalysis and the importance of regulating the structural dynamics of this loop through noncovalent

  20. 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.

  1. Subtasks affecting step-length asymmetry in post-stroke hemiparetic walking.

    PubMed

    Kim, Woo-Sub

    2016-10-01

    This study was performed to investigate whether components from trunk progression (TP) and step length were related to step length asymmetry in walking in patients with hemiparesis. Gait analysis was performed for participants with hemiparesis and healthy controls. The distance between the pelvis and foot in the anterior-posterior axis was calculated at initial-contact. Step length was partitioned into anterior foot placement (AFP) and posterior foot placement (PFP). TP was partitioned into anterior trunk progression (ATP) and posterior trunk progression (PTP). The TP pattern and step length pattern were defined to represent intra-TP and intra-step spatial balance, respectively. Of 29 participants with hemiparesis, nine participants showed longer paretic step length, eight participants showed symmetric step length, and 12 participants showed shorter paretic step length. For the hemiparesis group, linear regression analysis showed that ATP asymmetry, AFP asymmetry, and TP patterns had significant predictability regarding step length asymmetry. Prolonged paretic ATP and shortened paretic AFP was the predominant pattern in the hemiparesis group, even in participants with symmetric step length. However, some participants showed same direction of ATP and AFP asymmetry. These findings indicate the following: (1) ATP asymmetries should be observed to determine individual characteristics of step length asymmetry, and (2) TP patterns can provide complementary information for non-paretic limb compensation.

  2. 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.

  3. 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

  4. 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

  5. Reliability of the Spatiotemporal Determinants of Maximal Sprint Speed in Adolescent Boys Over Single and Multiple Steps.

    PubMed

    Meyers, Robert W; Oliver, Jon L; Hughes, Michael G; Lloyd, Rhodri Steffan; Cronin, John

    2015-08-01

    The purpose of this study was to examine the reliability of the spatiotemporal determinants of maximal sprinting speed in boys over single and multiple steps. Fifty-four adolescent boys (age = 14.1 ± 0.7 years [range = 12.9-15.7 years]; height = 1.63 ± 0.09 m; body mass = 55.3 ± 13.3 kg; -0.31 ± 0.90 age from Peak Height Velocity (PHV) in years; mean ± s) volunteered to complete a 30 m sprint test on 3 occasions over a 2-week period. Speed, step length, step frequency, contact time, and flight time were assessed via an optical measurement system. Speed and step characteristics were obtained from the single-fastest step and average of the 2 and 4 fastest consecutive steps. Pairwise comparison of consecutive trials revealed the coefficient of variation (CV) for speed was greater in 4-step (CV = 7.3 & 7.5%) compared with 2-step (CV = 4.2 & 4.1%) and 1-step (CV = 4.8 & 4.6%) analysis. The CV of step length, step frequency and contact time ranged from 4.8 to 7.5% for 1-step, 3.8-5.0% for 2-step and 4.2-7.5% for 4-step analyses across all trials. An acceptable degree of reliability was achieved for the spatiotemporal and performance variables assessed in this study. Two-step analysis demonstrated the highest degree of reliability for the key spatiotemporal variables, and therefore may be the most suitable approach to monitor the spatiotemporal characteristics of maximal sprint speed in boys.

  6. CRYPTIC PRECOCIOUS/MED12 is a Novel Flowering Regulator with Multiple Target Steps in Arabidopsis

    PubMed Central

    Imura, Yuri; Kobayashi, Yasushi; Yamamoto, Sumiko; Furutani, Masahiko; Tasaka, Masao; Abe, Mitsutomo; Araki, Takashi

    2012-01-01

    The proper timing of flowering is of crucial importance for reproductive success of plants. Regulation of flowering is orchestrated by inputs from both environmental and endogenous signals such as daylength, light quality, temperature and hormones, and key flowering regulators construct several parallel and interactive genetic pathways. This integrative regulatory network has been proposed to create robustness as well as plasticity of the regulation. Although knowledge of key genes and their regulation has been accumulated, there still remains much to learn about how they are organized into an integrative regulatory network. Here, we have analyzed the CRYPTIC PRECOCIOUS (CRP) gene for the Arabidopsis counterpart of the MED12 subunit of the Mediator. A novel dominant mutant, crp-1D, which causes up-regulation of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), FRUITFULL (FUL) and APETALA1 (AP1) expression in a FLOWERING LOCUS T (FT)-dependent manner, was identified in an enhancer screen of the early-flowering phenotype of 35S::FT. Genetic and molecular analysis of both crp-1D and crp loss-of-function alleles showed that MED12/CRP is required not only for proper regulation of SOC1, FUL and AP1, but also for up-regulation of FT, TWIN SISTER OF FT (TSF) and FD, and down-regulation of FLOWERING LOCUS C (FLC). These observations suggest that MED12/CRP is a novel flowering regulator with multiple regulatory target steps both upstream and downstream of the key flowering regulators including FT florigen. Our work, taken together with recent studies of other Mediator subunit genes, supports an emerging view that the Mediator plays multiple roles in the regulation of flowering. PMID:22247249

  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. Validation of the "Six Step Spot Test" for gait among patients with multiple sclerosis in Brazil.

    PubMed

    Pavan, Karina; Tilbery, Charles Peter; Lianza, Sergio; Marangoni, Bruna Eriko Matsuda

    2010-04-01

    The clinical manifestations of multiple sclerosis (MS) are variable among patients, and the course of disease is not linear. Different symptoms are presented, with gradual accumulation of disability. These variations are difficult to quantify in clinical practice, and several studies have attempted to create instruments capable of measuring these disabilities. The Six Step Spot Test (SSST) was developed for quantitative evaluation of the lower limbs (LL) over time. Performance in this test reflects the complexity of sensory-motor function, including LL strength, spasticity, coordination and balance, going beyond vision and cognition. The aim of the present study was to validate the SSST in a population of MS patients in Brazil. This prospective study included 75 patients with MS, with EDSS 0 to 6.5 in the study group. Ninety-one healthy subjects were randomly selected for the control group. The results showed that the groups were similar, and that the SSST is a reliable and reproducible test. According to the statistical analysis on the data in this study, the SSST is a valid, reliable and reproducible tool for use in the Brazilian MS patient population. PMID:20464285

  9. 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).

  10. 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

  11. Multiple weather factors affect apparent survival of European passerine birds.

    PubMed

    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

  12. 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.

  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. 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.

  15. Shapiro steps observed in a dc superconducting quantum interference device with multiple junctions in each arm

    NASA Astrophysics Data System (ADS)

    Chen, L.; Chen, P.; Ong, C. K.

    2002-02-01

    A high-Tc dc superconducting quantum interference device (SQUID) with three Josephson junctions (JJs) in series in each of its arms has been fabricated. Its Shapiro steps were studied using microwave (rf) radiation of 10 GHz and weak magnetic fields. The appearance of giant Shapiro steps and of some of half-integer steps was observed. Separation between the adjacent Shapiro steps could be tuned by rf magnetic fields and small external dc magnetic fields. This phenomenon was analyzed by phase locking the JJs in the SQUID.

  16. Simple tunable dual-wavelength fiber laser and multiple self-mixing interferometry to large step height measurement.

    PubMed

    Dong, Lianlian; Xie, Fang; Ma, Sen; Wang, Yunzhi; Chen, Liang

    2016-09-19

    A simple tunable dual-wavelength fiber laser was developed and multiple self-mixing interferometry to large step height measurement was demonstrated. The fiber laser, which can emit two wavelengths without laser mode competition, is composed of a single fiber ring cavity and two fiber branches. Each branch includes a length of erbium-doped fiber and a fiber Bragg grating. Large step heights can be measured using multiple self-mixing interference of the two wavelengths. The maximum height that can be measured is half synthetic wavelength of the two wavelengths. A step height of 2mm constructed with two gauge blocks has been measured. The standard deviation of measurement results is 2.5nm. PMID:27661923

  17. 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…

  18. 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

  19. 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…

  20. The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

    PubMed Central

    Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

    2014-01-01

    Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

  1. The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

    PubMed

    Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

    2015-09-01

    Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network.

  2. Real-space multiple scattering theory calculations of LEED (low-energy electron diffraction) intensities for stepped surfaces

    SciTech Connect

    Zhang, X.-G.; Rous, P.J.; Van Hove, M.A. ); MacLaren, J.M. ); Gonis, A. ); Somorjai, G.A. California Univ., Berkeley, CA . Dept. of Chemistry)

    1990-07-25

    We use a newly developed real-space multiple scattering theory (RS-MST) to calculate low-energy electron diffraction (LEED) intensities from stepped surfaces. In this calculation the electron wavefunctions are expanded in terms of an angular momentum basis, utilizing the property of removal invariance of systems with semi-infinite periodicity. This strongly reduces the dependence of the calculation on the interlayer spacing and thus opens up the possibility of treating more open surfaces. This includes in particular stepped surfaces, to which conventional methods cannot be applied. Applications of the formalism to various stepped surfaces are presented. In particular, the results for Cu(311) and (331) surfaces obtained from both the layer doubling and RS-MST methods are compared. In addition, numerical techniques which can improve the convergence as well as the speed of the RS-MST approach are discussed. 6 refs., 3 figs.

  3. 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

  4. 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

  5. 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

    NASA Astrophysics Data System (ADS)

    Omelyan, Igor; Kovalenko, Andriy

    2013-12-01

    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

  6. Efficient multiple-time-step integrators with distance-based force splitting for particle-mesh-Ewald molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Qian, Xiaoliang; Schlick, Tamar

    2002-04-01

    We develop an efficient multiple-time-step force splitting scheme for particle-mesh-Ewald molecular dynamics simulations. Our method exploits smooth switch functions effectively to regulate direct and reciprocal space terms for the electrostatic interactions. The reciprocal term with the near field contributions removed is assigned to the slow class; the van der Waals and regulated particle-mesh-Ewald direct-space terms, each associated with a tailored switch function, are assigned to the medium class. All other bonded terms are assigned to the fast class. This versatile protocol yields good stability and accuracy for Newtonian algorithms, with temperature and pressure coupling, as well as for Langevin dynamics. Since the van der Waals interactions need not be cut at short distances to achieve moderate speedup, this integrator represents an enhancement of our prior multiple-time-step implementation for microcanonical ensembles. Our work also tests more rigorously the stability of such splitting schemes, in combination with switching methodology. Performance of the algorithms is optimized and tested on liquid water, solvated DNA, and solvated protein systems over 400 ps or longer simulations. With a 6 fs outer time step, we find computational speedup ratios of over 6.5 for Newtonian dynamics, compared with 0.5 fs single-time-step simulations. With modest Langevin damping, an outer time step of up to 16 fs can be used with a speedup ratio of 7.5. Theoretical analyses in our appendices produce guidelines for choosing the Langevin damping constant and show the close relationship among the leapfrog Verlet, velocity Verlet, and position Verlet variants.

  7. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  8. Micro-plasticity of surface steps under adhesive contact: Part II—Multiple-dislocation mediated contact hardening

    NASA Astrophysics Data System (ADS)

    Gao, Y. F.; Yu, H. H.; Kim, K.-S.

    The study of micro-plastic behavior of rough surface contacts is the critical link towards a fundamental understanding of contact, friction, adhesion, and surface failures at small length scales. In the companion paper (Yu, H.H., Shrotriya, P., Gao, Y.F., Kim, K.-S., 2007. Micro-plasticity of surface steps under adhesive contact. Part I. Surface yielding controlled by single-dislocation nucleation. J. Mech. Phys. Solids 55, 489-516), we have studied the onset of surface yielding due to single-dislocation nucleation from a stepped surface under adhesive contact. Here we analyze the contact hardening behavior due to multiple dislocations in a two-dimensional dislocation model. Continuum micro-mechanical analyses are used to derive the configurational force on the dislocation, while a modified Rice-Thomson criterion is used to model dislocation nucleation. Dislocations nucleated from the surface step are stabilized and pile up as a result of the balance between the resolved driving force and the non-zero lattice resistance in the solid. The dislocation pileup will exert a strong back stress to prevent further dislocation nucleation and thus lead to the contact hardening behavior, the degree of which depends on the slip-plane orientation. Particularly, we find that dislocation interactions between two slip planes can make the contact loading order-of-magnitude easy to nucleate multiple dislocations, which is thus named "latent softening". A mechanistic explanation shows that the latent softening is closely related to the stress-concentration mode mixity at the surface step. Dislocation nucleation will modify the geometric characteristics of the surface step, so that the contact-induced stress state near the step, as described by the mode mixity, changes, which influences the subsequent dislocation nucleation. Our calculations show that the dislocation pileup on one slip plane can even cause the spontaneous dislocation nucleation on the other slip plane without further

  9. Systems biology approach in Chlamydomonas reveals connections between copper nutrition and multiple metabolic steps.

    PubMed

    Castruita, Madeli; Casero, David; Karpowicz, Steven J; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I; Yan, Weihong; Cokus, Shawn; Loo, Joseph A; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S

    2011-04-01

    In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O₂-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper.

  10. 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

  11. Development of a multiple-step process for the microbial decontamination of beef trim.

    PubMed

    Kang, D H; Koohmaraie, M; Dorsa, W J; Siragusa, G R

    2001-01-01

    A multiple-hurdle antimicrobial process for beef trim was developed. The microbial profiles of inoculated lean beef trim tissue (BTL) and fat-covered lean beef trim (BTF) were monitored during prolonged refrigerated storage following the application of successive multiple antimicrobial treatments applied to inoculated beef trim on a processing conveyor belt set at a belt speed of 1 cm/s. Beef trim (meat size approximately 15 by 15 cm) was preinoculated with bovine feces before all treatments that included the following: control, no treatment; water wash at 65 psi for five passes; water plus lactic acid (2% [vol/vol] room temperature lactic acid wash at 30 psi for three passes); combination treatment 1 (water plus 65 degrees C hot water at 30 psi for one pass plus hot air at 510 degrees C for four passes plus lactic acid), combination treatment 2 (water plus hot water at 82 degrees C for one pass plus hot air at 510 degrees C for five passes plus lactic acid), and combination treatment 3 (water plus hot water at 82 degrees C for three passes plus hot air at 510 degrees C for six passes plus lactic acid). The effects of treatments on bacterial populations were monitored by enumerating mesophilic aerobic bacteria (APC), presumptive lactic acid bacteria (PLAB), psychrotrophic bacteria (PCT), coliforms, and Escherichia coli biotype 1 on product stored for up to 7 days at 4 degrees C. In the case of BTL, the numbers of APC, PCT, and PLAB increased during storage at 5 degrees C, whereas the numbers of coliform and E. coli decreased on average by 1.8 log CFU/cm2, then remained constant following the initial reduction. Negligible effects on color quality were observed from multihurdle treatment combination 1. In the case of the BTF, the microbial reductions by treatments were much greater than the reduction on BTL. The pH of treated BTF increased more slowly than the pH of treated BTL, resulting in further reduction of the microflora on BTF. Except for control and water

  12. Efficient multiple time step method for use with Ewald and particle mesh Ewald for large biomolecular systems

    NASA Astrophysics Data System (ADS)

    Zhou, Ruhong; Harder, Edward; Xu, Huafeng; Berne, B. J.

    2001-08-01

    The particle-particle particle-mesh (P3M) method for calculating long-range electrostatic forces in molecular simulations is modified and combined with the reversible reference system propagator algorithm (RESPA) for treating the multiple time scale problems in the molecular dynamics of complex systems with multiple time scales and long-range forces. The resulting particle-particle particle-mesh Ewald RESPA (P3ME/RESPA) method provides a fast and accurate representation of the long-range electrostatic interactions for biomolecular systems such as protein solutions. The method presented here uses a different breakup of the electrostatic forces than was used by other authors when they combined the Particle Mesh Ewald method with RESPA. The usual breakup is inefficient because it treats the reciprocal space forces in an outer loop even though they contain a part that changes rapidly in time. This does not allow use of a large time step for the outer loop. Here, we capture the short-range contributions in the reciprocal space forces and include them in the inner loop, thereby allowing for larger outer loop time steps and thus for a much more efficient RESPA implementation. The new approach has been applied to both regular Ewald and P3ME. The timings of Ewald/RESPA and P3ME/RESPA are compared in detail with the previous approach for protein water solutions as a function of number of atoms in the system, and significant speedups are reported.

  13. RAB5 activation is required for multiple steps in Arabidopsis thaliana root development.

    PubMed

    Inoue, Takeshi; Kondo, Yuki; Naramoto, Satoshi; Nakano, Akihiko; Ueda, Takashi

    2013-10-01

    Rab GTPases regulate the tethering and fusion of transport vesicles to target membranes in membrane trafficking by acting as a molecular switch, cycling between GDP- and GTP-bound states. RAB5 is a member of the Rab GTPase family, the members of which have been shown to perform various functions in the endocytic pathway, including the regulation of endosomal fusion and motility in animal cells. RAB5-mediated endosomal trafficking has also been found to play important roles in various higher order plant functions, which include the regulation of the polar transport of auxin and responses to environmental conditions. The regulatory mechanisms and functions of plant RAB5 have also been investigated at the molecular and cellular levels. However, the significance of RAB5 activity at the tissue and organ levels has hardly been investigated thus far. In the present study, we examined the effect of a mutation in VPS9a, which encodes the sole guanine nucleotide exchange factor for all RAB5s in the vegetative stages of Arabidopsis thaliana. We found that multiple developmental processes were impaired in the mutant plants, including the growth and pattern formation of the roots and establishment of auxin maxima. Our results indicate that RAB5 plays distinctive pivotal roles in the development of plants.

  14. Comparison of the phenolic composition of fruit juices by single step gradient HPLC analysis of multiple components versus multiple chromatographic runs optimised for individual families.

    PubMed

    Bremner, P D; Blacklock, C J; Paganga, G; Mullen, W; Rice-Evans, C A; Crozier, A

    2000-06-01

    After minimal sample preparation, two different HPLC methodologies, one based on a single gradient reversed-phase HPLC step, the other on multiple HPLC runs each optimised for specific components, were used to investigate the composition of flavonoids and phenolic acids in apple and tomato juices. The principal components in apple juice were identified as chlorogenic acid, phloridzin, caffeic acid and p-coumaric acid. Tomato juice was found to contain chlorogenic acid, caffeic acid, p-coumaric acid, naringenin and rutin. The quantitative estimates of the levels of these compounds, obtained with the two HPLC procedures, were very similar, demonstrating that either method can be used to analyse accurately the phenolic components of apple and tomato juices. Chlorogenic acid in tomato juice was the only component not fully resolved in the single run study and the multiple run analysis prior to enzyme treatment. The single run system of analysis is recommended for the initial investigation of plant phenolics and the multiple run approach for analyses where chromatographic resolution requires improvement.

  15. 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

  16. [Integrated risk evaluation of multiple disasters affecting longyan yield in Fujian Province, East China].

    PubMed

    Chen, Jia-Jin; Wang, Jia-Yi; Li, Li-Chun; Lin, Jing; Yang, Kai; Ma, Zhi-Guo; Xu, Zong-Huan

    2012-03-01

    In this study, an index system for the integrated risk evaluation of multiple disasters on the Longyan production in Fujian Province was constructed, based on the analysis of the major environmental factors affecting the Longyan growth and yield, and from the viewpoints of potential hazard of disaster-causing factors, vulnerability of hazard-affected body, and disaster prevention and mitigation capability of Longyan growth regions in the Province. In addition, an integrated evaluation model of multiple disasters was established to evaluate the risks of the major agro-meteorological disasters affecting the Longyan yield, based on the yearly meteorological data, Longyan planting area and yield, and other socio-economic data in Longyan growth region in Fujian, and by using the integral weight of risk indices determined by AHP and entropy weight coefficient methods. In the Province, the Longyan growth regions with light integrated risk of multiple disasters were distributed in the coastal counties (except Dongshan County) with low elevation south of Changle, the regions with severe and more severe integrated risk were mainly in Zhangping of Longyan, Dongshan, Pinghe, Nanjin, and Hua' an of Zhangzhou, Yongchun and Anxi of Quanzhou, north mountainous areas of Putian and Xianyou, Minqing, Minhou, Luoyuan, and mountainous areas of Fuzhou, and Fuan, Xiapu, and mountainous areas of Ninde, among which, the regions with severe integrated risk were in Dongshan, Zhangping, and other mountainous areas with high altitudes, and the regions with moderate integrated risk were distributed in the other areas of the Province.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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…

  3. Sodium phenylacetate inhibits adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice at multiple steps.

    PubMed

    Dasgupta, Subhajit; Zhou, You; Jana, Malabendu; Banik, Naren L; Pahan, Kalipada

    2003-04-01

    Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. The present study underlines the importance of sodium phenylacetate (NaPA), a drug approved for urea cycle disorders, in inhibiting the disease process of adoptively transferred EAE in female SJL/J mice at multiple steps. Myelin basic protein (MBP)-primed T cells alone induced the expression of NO synthase (iNOS) and the activation of NF-kappaB in mouse microglial cells through cell-cell contact. However, pretreatment of MBP-primed T cells with NaPA markedly inhibited its ability to induce microglial expression of iNOS and activation of NF-kappaB. Consistently, adoptive transfer of MBP-primed T cells, but not that of NaPA-pretreated MBP-primed T cells, induced the clinical symptoms of EAE in female SJL/J mice. Furthermore, MBP-primed T cells isolated from NaPA-treated donor mice were also less efficient than MBP-primed T cells isolated from normal donor mice in inducing iNOS in microglial cells and transferring EAE to recipient mice. Interestingly, clinical symptoms of EAE were much less in mice receiving NaPA through drinking water than those without NaPA. Similar to NaPA, sodium phenylbutyrate, a chemically synthesized precursor of NaPA, also inhibited the disease process of EAE. Histological and immunocytochemical analysis showed that NaPA inhibited EAE-induced spinal cord mononuclear cell invasion and normalized iNOS, nitrotyrosine, and p65 (the RelA subunit of NF-kappaB) expression within the spinal cord. Taken together, our results raise the possibility that NaPA or sodium phenylbutyrate taken through drinking water or milk may reduce the observed neuroinflammation and disease process in multiple sclerosis patients. PMID:12646656

  4. 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.

  5. Scanning for MODY5 gene mutations in Chinese early onset or multiple affected diabetes pedigrees.

    PubMed

    Wang, C; Fang, Q; Zhang, R; Lin, X; Xiang, K

    2004-12-01

    Mutation of HNF-1beta gene has been reported in early onset diabetes or MODY families and this gene has been defined as MODY5 gene. The aim of our study was to examine whether HNF-1beta mutation contribute to early onset or multiple affected diabetes pedigrees in Chinese. Molecular scanning of HNF-1beta gene promoter region, nine exons and flanking introns was performed in 154 unrelated probands from early onset and multiple affected diabetes Chinese pedigrees. The family members of probands with mutations or variants and 58 nondiabetics were also examined. Clinical examinations of renal morphology, renal function and beta-cell function were performed in the HNF-1beta gene mutation carriers and family members. Mutation of HNF-1beta gene causing the substitution S36F was found in two subjects of an early onset diabetic family. One carrier has early onset diabetes, renal function impairment and renal cyst, while the other has impaired glucose tolerance only. This is the first case of MODY5 gene mutation diabetes found in the Chinese. Three HNF-1beta variants were identified and no significant differences in allele frequencies for these variants were detected between the nondiabetic and diabetic groups. Nucleotide 66 of intron 8 of HNF-1beta gene was G in the Chinese population rather than A as noted in the GenBank sequence. These results suggest that HNF-1beta gene mutations may be associated with nondiabetic renal dysfunction and diabetes in Chinese, but they are responsible for only a small percentage of early onset or multiple affected diabetes pedigrees including MODY. PMID:15660195

  6. 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.

  7. Mechanisms of adaptation from a multiple to a single step recovery strategy following repeated exposure to forward loss of balance in older adults.

    PubMed

    Carty, Christopher P; Cronin, Neil J; Lichtwark, Glen A; Mills, Peter M; Barrett, Rod S

    2012-01-01

    When released from an initial, static, forward lean angle and instructed to recover with a single step, some older adults are able to meet the task requirements, whereas others either stumble or fall. The purpose of the present study was to use the concept of margin of stability (MoS) to investigate balance recovery responses in the anterior-posterior direction exhibited by older single steppers, multiple steppers and those that are able to adapt from multiple to single steps following exposure to repeated forward loss of balance. One hundred and fifty-one healthy, community dwelling, older adults, aged 65-80 years, participated in the study. Participants performed four trials of the balance recovery task from each of three initial lean angles. Balance recovery responses in the anterior-posterior direction were quantified at three events; cable release (CR), toe-off (TO) and foot contact (FC), for trials performed at the intermediate lean angle. MoS was computed as the anterior-posterior distance between the forward boundary of the Base of Support (BoS) and the vertical projection of the velocity adjusted centre of mass position (XCoM). Approximately one-third of participants adapted from a multiple to a single step recovery strategy following repeated exposure to the task. MoS at FC for the single and multiple step trials in the adaptation group were intermediate between the exclusively single step group and the exclusively multiple step group, with the single step trials having a significant, 3.7 times higher MoS at FC than the multiple step trials. Consistent with differences between single and multiple steppers, adaptation from multiple to single steps was attributed to an increased BoS at FC, a reduced XCoM at FC and an increased rate of BoS displacement from TO to FC. Adaptations occurred within a single test session and suggest older adults that are close to the threshold of successful recovery can rapidly improve dynamic stability following repeated

  8. 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.

  9. 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

  10. 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

  11. 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…

  12. Cyclosporin A differentially inhibits multiple steps in VEGF induced angiogenesis in human microvascular endothelial cells through altered intracellular signaling

    PubMed Central

    Rafiee, Parvaneh; Heidemann, Jan; Ogawa, Hitoshi; Johnson, Nathan A; Fisher, Pamela J; Li, Mona S; Otterson, Mary F; Johnson, Christopher P; Binion, David G

    2004-01-01

    The immunosuppressive agent cyclosporin A (CsA), a calcineurin inhibitor which blocks T cell activation has provided the pharmacologic foundation for organ transplantation. CsA exerts additional effects on non-immune cell populations and may adversely effect microvascular endothelial cells, contributing to chronic rejection, a long-term clinical complication and significant cause of mortality in solid-organ transplants, including patients with small bowel allografts. Growth of new blood vessels, or angiogenesis, is a critical homeostatic mechanism in organs and tissues, and regulates vascular populations in response to physiologic requirements. We hypothesized that CsA would inhibit the angiogenic capacity of human gut microvessels. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were used to evaluate CsA's effect on four in vitro measures of angiogenesis, including endothelial stress fiber assembly, migration, proliferation and tube formation, in response to the endothelial growth factor VEGF. We characterized the effect of CsA on intracellular signaling mechanisms following VEGF stimulation. CsA affected all VEGF induced angiogenic events assessed in HIMEC. CsA differentially inhibited signaling pathways which mediated distinct steps of the angiogenic process. CsA blocked VEGF induced nuclear translocation of the transcription factor NFAT, activation of p44/42 MAPK, and partially inhibited JNK and p38 MAPK. CsA differentially affected signaling cascades in a dose dependent fashion and completely blocked expression of COX-2, which was integrally linked to HIMEC angiogenesis. These data suggest that CsA inhibits the ability of microvascular endothelial cells to undergo angiogenesis, impairing vascular homeostatic mechanisms and contributing to the vasculopathy associated with chronic rejection. PMID:15175101

  13. Multiple step growth of single crystalline rutile nanorods with the assistance of self-assembled monolayer for dye sensitized solar cells.

    PubMed

    Yang, Mengjin; Neupane, Suman; Wang, Xuewen; He, Jin; Li, Wenzhi; Pala, Nezih

    2013-10-01

    A novel multiple step growth (MSG) process has been developed to synthesize rutile nanorods (NRs) on fluorine-doped tin oxide (FTO) glass with the assistance of a self-assembled monolayer (SAM) aiming to increase the internal surface area of the 1D materials for dye sensitized solar cell (DSSC) applications. The experimental result reveals that the SAM layer can be selectively decomposed at the tip of the nanorod, namely the rutile (001) surface, due to the anisotropic photocatalytic property of the rutile. The remaining SAM layer on the side-wall of the NRs remains intact and serves as water repellent which prevents the radial growth of the NRs during the next step hydrothermal synthesis; therefore, the spacing between the NRs and the porosity of the NR array can be retained after additional growth cycles. On the other hand, introduction of a middle layer formed via TiCl4 solution treatment before the next growth cycle is found to be an effective way to control the diameters of the newly grown NRs. The performance of DSSC made from the rutile NRs grown using the MSG technique has been examined, and it is significantly affected by the internal surfaces of the NRs. Furthermore, the MSG combined with NR etching treatment by acid at low temperature (150 °C) leads to a significant enhancement in the solar cell performance. The gigantic wettability difference of the NRs before and after the SAM treatment as well as the MSG method could be adapted to prepare superhydrophobic and superhydrophilic nanostructured patterns for other applications.

  14. 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

  15. 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.

  16. 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

  17. Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty

    PubMed Central

    2010-01-01

    Background The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity. Results We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling. Conclusions This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots) and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling). Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a genomic region containing

  18. 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…

  19. 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

  20. 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

  1. Multiple Yeast Genes, Including Paf1 Complex Genes, Affect Telomere Length via Telomerase RNA Abundance▿ †

    PubMed Central

    Mozdy, Amy D.; Podell, Elaine R.; Cech, Thomas R.

    2008-01-01

    Twofold reductions in telomerase RNA levels cause telomere shortening in both humans and the yeast Saccharomyces cerevisiae. To test whether multiple genes that affect telomere length act by modulating telomerase RNA abundance, we used real-time reverse transcription-PCR to screen S. cerevisiae deletion strains reported to maintain shorter or longer telomeres to determine the levels of their telomerase RNA (TLC1) abundance. Of 290 strains screened, 5 had increased TLC1 levels; 4 of these maintained longer telomeres. Twenty strains had decreased TLC1 levels; 18 of these are known to maintain shorter telomeres. Four strains with decreased TLC1 RNA levels contained deletions of subunits of Paf1C (polymerase II-associated factor complex). While Paf1C had been implicated in the transcription of both polyadenylated and nonpolyadenylated RNAs, Paf1C had not been associated previously with the noncoding telomerase RNA. In Paf1C mutant strains, TLC1 overexpression partially rescues telomere length and cell growth defects, suggesting that telomerase RNA is a critical direct or indirect Paf1C target. Other factors newly identified as affecting TLC1 RNA levels include cyclin-dependent kinase, the mediator complex, protein phosphatase 2A, and ribosomal proteins L13B and S16A. This report establishes that a subset of telomere length genes act by modulating telomerase RNA abundance. PMID:18411302

  2. 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…

  3. Comparison of primary lung tumor incidences in the rat evaluated by the standard microscopy method and by multiple step sections.

    PubMed

    Kolling, Angelika; Ernst, Heinrich; Rittinghausen, Susanne; Heinrich, Uwe; Pott, Friedrich

    2008-08-01

    approximate value of the whole tumor volume was calculated. The detection of tumors with a diameter of 0.25mm was possible. Based on the size distribution of 75 tumor volumes, the probability of detecting a tumor was 86% when using 12 sections. The addition of step sections enhanced the tumor detection rate from 17 to a total number of 44 lung tumors in the quartz-treated rats, from 6 to 10 in the quartz- and PVNO-treated rats, from 4 to 11 in the amorphous SiO(2)-treated rats, and from 4 to 10 in the carbon black-treated rats. Both the tumor multiplicity and the number of rats with pre-neoplastic lesions increased. These additional data corroborated the initial findings in all experimental groups and provided statistically significant results confirming the equivocal evidence of carcinogenic activity of amorphous SiO(2) in female Wistar rats. This technique offered accurate information on the incidence, histological type, size, and location of proliferative lesions in the entire lung, but the benefit must be balanced against the extra financial effort.

  4. BDNF val66met Polymorphism Affects Aging of Multiple Types of Memory

    PubMed Central

    Kennedy, Kristen M.; Reese, Elizabeth D.; Horn, Marci M.; Sizemore, April N.; Unni, Asha K.; Meerbrey, Michael E.; Kalich, Allan G.; Rodrigue, Karen M.

    2014-01-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age x BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p < .07) toward poorer associative memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory – in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). PMID:25264352

  5. 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.

  6. A split-step method to include electron-electron collisions via Monte Carlo in multiple rate equation simulations

    NASA Astrophysics Data System (ADS)

    Huthmacher, Klaus; Molberg, Andreas K.; Rethfeld, Bärbel; Gulley, Jeremy R.

    2016-10-01

    A split-step numerical method for calculating ultrafast free-electron dynamics in dielectrics is introduced. The two split steps, independently programmed in C++11 and FORTRAN 2003, are interfaced via the presented open source wrapper. The first step solves a deterministic extended multi-rate equation for the ionization, electron-phonon collisions, and single photon absorption by free-carriers. The second step is stochastic and models electron-electron collisions using Monte-Carlo techniques. This combination of deterministic and stochastic approaches is a unique and efficient method of calculating the nonlinear dynamics of 3D materials exposed to high intensity ultrashort pulses. Results from simulations solving the proposed model demonstrate how electron-electron scattering relaxes the non-equilibrium electron distribution on the femtosecond time scale.

  7. Measurement and characterization of a nano-scale multiple-step height sample using a stylus profiler

    NASA Astrophysics Data System (ADS)

    Li, Changsheng; Yang, Shuming; Wang, Yiming; Wang, Chenying; Ren, Wei; Jiang, Zhuangde

    2016-11-01

    In this paper, we discussed a method for the measurement and characterization of a three-step height sample using a stylus profiler. The original measurement data were processed by a polynomial fitting based algorithm to reduce low frequency artefacts. A low pass filter with the cutoff frequency of 0.8/μm was used to remove the high frequency noise, and a ten order polynomial was used to effectively remove the low frequency artefacts. The experimental results indicated that the uncertainties of the step heights were between 1 nm and 2.2 nm. Furthermore, the deposition rate of the step films with uncertainty was calculated as an application of the sample measurement. The results indicate that the deposition rate for the step films based on the measurement of the stylus profiler was consistent with that of a spectroscopic ellipsometer.

  8. Multiple and diverse structural changes affect the breakpoint regions of polymorphic inversions across the Drosophila genus

    PubMed Central

    Puerma, Eva; Orengo, Dorcas J.; Aguadé, Montserrat

    2016-01-01

    Chromosomal polymorphism is widespread in the Drosophila genus, with extensive evidence supporting its adaptive character in diverse species. Moreover, inversions are the major contributors to the genus chromosomal evolution. The molecular characterization of a reduced number of polymorphic inversion breakpoints in Drosophila melanogaster and Drosophila subobscura supports that their inversions would have mostly originated through a mechanism that generates duplications —staggered double-strand breaks— and has thus the potential to contribute to their adaptive character. There is also evidence for inversion breakpoint reuse at different time scales. Here, we have characterized the breakpoints of two inversions of D. subobscura —O4 and O8— involved in complex arrangements that are frequent in the warm parts of the species distribution area. The duplications detected at their breakpoints are consistent with their origin through the staggered-break mechanism, which further supports it as the prevalent mechanism in D. subobscura. The comparative analysis of inversions breakpoint regions across the Drosophila genus has revealed several genes affected by multiple disruptions due not only to inversions but also to single-gene transpositions and duplications. PMID:27782210

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    PubMed

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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 &…

  2. Realistic changes in seaweed biodiversity affect multiple ecosystem functions on a rocky shore.

    PubMed

    Bracken, Matthew E S; Williams, Susan L

    2013-09-01

    Given current threats to biodiversity, understanding the effects of diversity changes on the functions and services associated with intact ecosystems is of paramount importance. However, limited realism in most biodiversity studies makes it difficult to link the large and growing body of evidence for important functional consequences of biodiversity change to real-world losses of biodiversity. Here, we explored two methods of incorporating realism into biodiversity research: (1) the use of two-, five-, and eight-species assemblages that mimicked those that we observed in surveys of seaweed biodiversity patterns on a northern California (USA) rocky shore and the explicit comparison of those assemblages to random assemblages compiled from the same local species pool; and (2) the measurement of two fundamental ecosystem functions, nitrate uptake and photosynthesis, both of which contribute to growth of primary producers. Specifically, we measured nitrate uptake rates of seaweed assemblages as a function of initial nitrate concentrations and photosynthetic rates as a function of irradiance levels for both realistic and random assemblages of seaweeds. We only observed changes in ecosystem functioning along a richness gradient for realistic assemblages, and both maximum nitrate uptake rates (V(max)) and photosynthetic light use efficiency values (alpha(p) = P(max)/I(K)) were higher in realistic assemblages than in random assemblages. Furthermore, the parameter affected by changes in richness depended on the function being measured. Both V(max) and alpha(p) declined with increasing richness in nonrandom assemblages due to a combination of species identity effects (for V(max) and overyielding effects (for both V(max) and alpha(p)). In contrast, neither nitrate uptake efficiency values (alpha(N) = V(max)/K(s)), nor maximum photosynthetic rates (Pmax) changed along the gradient in seaweed species richness. Furthermore, overyielding was only evident in realistic assemblages

  3. One-step preparation of macroporous polymer particles with multiple interconnected chambers: a candidate for trapping biomacromolecules.

    PubMed

    Qian, Qiuping; Huang, Xiaopeng; Zhang, Xinyue; Xie, Zhigang; Wang, Yapei

    2013-09-27

    Taking advantage of photothermal conversion, the surface pores of water-dispersible single-walled carbon nanotubes assembled on polymer particles were rapidly closed by NIR irradiation to produce macroporous polymeric microspheres with multiple interconnected chambers. These particles can act as smart containers to encapsulate and hold DNA molecules.

  4. Building the Bridge between Home and School: One Rural School's Steps to Interrogate and Celebrate Multiple Literacies

    ERIC Educational Resources Information Center

    Hansen, Faith Beyer

    2009-01-01

    This paper examines one rural school's efforts to recognize and celebrate the multiple literacies of its students, by hosting a LINK Up family night that highlights the varied funds of knowledge of school, community and home. In dialogue with excerpts from Sherman Alexie's novel, "The Absolute True Diaries of a Part Time Indian," the paper…

  5. 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

  6. Cellulose nanofibrils for one-step stabilization of multiple emulsions (W/O/W) based on soybean oil.

    PubMed

    Carrillo, Carlos A; Nypelö, Tiina E; Rojas, Orlando J

    2015-05-01

    Cellulose nanofibrils (CNF) were incorporated in water-in-oil (W/O) microemulsions and emulsions, as well as water-in-oil-in-water (W/O/W) multiple emulsions using soybean oil. The addition of CNF to the aqueous phase expanded the composition range to obtain W/O/W emulsions. CNF also increased the viscosity of the continuous phase and reduced the drop size both of which increased the stability and effective viscosity of the emulsions. The effects of oil type and polarity on the properties of the W/O/W emulsions were tested with limonene and octane, which compared to soybean oil produced a smaller emulsion drop size, and thus a higher emulsion viscosity. Overall, CNF are a feasible alternative to conventional polysaccharides as stability enhancers for normal and multiple emulsions that exhibit strong shear thinning behavior.

  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-step model-experiment matching allows precise definition of dynamical leg parameters in human running.

    PubMed

    Ludwig, C; Grimmer, S; Seyfarth, A; Maus, H-M

    2012-09-21

    The spring-loaded inverted pendulum (SLIP) model is a well established model for describing bouncy gaits like human running. The notion of spring-like leg behavior has led many researchers to compute the corresponding parameters, predominantly stiffness, in various experimental setups and in various ways. However, different methods yield different results, making the comparison between studies difficult. Further, a model simulation with experimentally obtained leg parameters typically results in comparatively large differences between model and experimental center of mass trajectories. Here, we pursue the opposite approach which is calculating model parameters that allow reproduction of an experimental sequence of steps. In addition, to capture energy fluctuations, an extension of the SLIP (ESLIP) is required and presented. The excellent match of the models with the experiment validates the description of human running by the SLIP with the obtained parameters which we hence call dynamical leg parameters.

  9. A fully automatic three-step liver segmentation method on LDA-based probability maps for multiple contrast MR images.

    PubMed

    Gloger, Oliver; Kühn, Jens; Stanski, Adam; Völzke, Henry; Puls, Ralf

    2010-07-01

    Automatic 3D liver segmentation in magnetic resonance (MR) data sets has proven to be a very challenging task in the domain of medical image analysis. There exist numerous approaches for automatic 3D liver segmentation on computer tomography data sets that have influenced the segmentation of MR images. In contrast to previous approaches to liver segmentation in MR data sets, we use all available MR channel information of different weightings and formulate liver tissue and position probabilities in a probabilistic framework. We apply multiclass linear discriminant analysis as a fast and efficient dimensionality reduction technique and generate probability maps then used for segmentation. We develop a fully automatic three-step 3D segmentation approach based upon a modified region growing approach and a further threshold technique. Finally, we incorporate characteristic prior knowledge to improve the segmentation results. This novel 3D segmentation approach is modularized and can be applied for normal and fat accumulated liver tissue properties.

  10. Regeneration of glass nanofluidic chips through a multiple-step sequential thermochemical decomposition process at high temperatures.

    PubMed

    Xu, Yan; Wu, Qian; Shimatani, Yuji; Yamaguchi, Koji

    2015-10-01

    Due to the lack of regeneration methods, the reusability of nanofluidic chips is a significant technical challenge impeding the efficient and economic promotion of both fundamental research and practical applications on nanofluidics. Herein, a simple method for the total regeneration of glass nanofluidic chips was described. The method consists of sequential thermal treatment with six well-designed steps, which correspond to four sequential thermal and thermochemical decomposition processes, namely, dehydration, high-temperature redox chemical reaction, high-temperature gasification, and cooling. The method enabled the total regeneration of typical 'dead' glass nanofluidic chips by eliminating physically clogged nanoparticles in the nanochannels, removing chemically reacted organic matter on the glass surface and regenerating permanent functional surfaces of dissimilar materials localized in the nanochannels. The method provides a technical solution to significantly improve the reusability of glass nanofluidic chips and will be useful for the promotion and acceleration of research and applications on nanofluidics.

  11. Combining versus Analyzing Multiple Causes: How Domain Assumptions and Task Context Affect Integration Rules

    ERIC Educational Resources Information Center

    Waldmann, Michael R.

    2007-01-01

    In everyday life, people typically observe fragments of causal networks. From this knowledge, people infer how novel combinations of causes they may never have observed together might behave. I report on 4 experiments that address the question of how people intuitively integrate multiple causes to predict a continuously varying effect. Most…

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Peer Rated Therapeutic Talent and Affective Sensitivity: A Multiple Regression Approach.

    ERIC Educational Resources Information Center

    Jackson, Eugene

    1985-01-01

    Used peer rated measures of Warmth, Understanding and Openness to predict scores on the Kagan Affective Sensitivity Scale-E80 among 66 undergraduates who had participated in interpersonal skills training groups. Results indicated that, as an additively composite index of Therapeutic Talent, they were positively correlated with affective…

  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. 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...

  19. 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

  20. 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.

  1. 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. PMID:27621653

  2. How do Data Processing Choices Affect Multiple Aperture InSAR (MAI) Precision?

    NASA Astrophysics Data System (ADS)

    Bechor-Ben Dov, N.

    2015-12-01

    MAI data processing methods report different precisions, sometimes for the same data; we investigate these discrepancies here. MAI, a method to obtain phase-based along-track displacements from InSAR data, has been used for measuring volcanic, glacier, and earthquake displacements. However, different applications show vastly different precisions, ranging from a few millimeters to tens of centimeters per interferogram. While some spatial variability in precision is expected due to the InSAR phase noise dependence on terrain, some reports show different precisions for the same data. Here, I address the following questions: What is the true precision of MAI measurements? What are the MAI noise sources, and how do we mitigate them? We use data from 11 Envisat, 2 ERS, and 1 ALOS interferograms to analyze and quantify the MAI noise sources and their dependence on the method's implementation. To do that, we implement various processing steps with the JPL/Caltech InSAR data processor ROI_PAC. We find that there are several (sometimes surprising) nuances in data processing that together can reduce scatter noise by half, and other corrections that can reduce topography-related noise by up to 25 centimeters. We find that even with all the optimized data processing steps, the actual MAI errors (relative accuracy) are higher then the theoretical ones by a factor that depends on filter window size. We present an updated MAI data processor, which is capable of achieving relative accuracy and precision levels of 6 to 2 centimeters, respectively, in low to medium coherence terrains (correlation coefficient of 0.4 to 0.8), and provides error estimates that better reflect the actual relative accuracy of the measurement.

  3. Food restriction negatively affects multiple levels of the reproductive axis in male house finches, Haemorhous mexicanus.

    PubMed

    Valle, Shelley; Carpentier, Elodie; Vu, Bethany; Tsutsui, Kazuyoshi; Deviche, Pierre

    2015-09-01

    Nutrition influences reproductive functions across vertebrates, but the effects of food availability on the functioning of the hypothalamic-pituitary-gonadal (HPG) axis in wild birds and the mechanisms mediating these effects remain unclear. We investigated the influence of chronic food restriction on the HPG axis of photostimulated house finches, Haemorhous mexicanus. Food-restricted birds had underdeveloped testes with smaller seminiferous tubules than ad libitum-fed birds. Baseline plasma testosterone increased in response to photostimulation in ad libitum-fed but not in food-restricted birds. Food availability did not, however, affect the plasma testosterone increase resulting from a gonadotropin-releasing hormone-I (GnRH) or a luteinizing hormone (LH) challenge. The number of hypothalamic GnRH immunoreactive (ir) but not proGnRH-ir perikarya was higher in food-restricted than in ad libitum-fed finches, suggesting inhibited secretion of GnRH. Hypothalamic gonadotropin-inhibitory hormone (GnIH)-ir and neuropeptide Y (NPY)-ir were not affected by food availability. Plasma corticosterone (CORT) was also not affected by food availability, indicating that the observed HPG axis inhibition did not result from increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. This study is among the first to examine multilevel functional changes in the HPG axis in response to food restriction in a wild bird. The results indicate that food availability affects both hypothalamic and gonadal function, but further investigations are needed to clarify the mechanisms by which nutritional signals mediate these effects.

  4. Shade affects responses to drought and flooding - acclimation to multiple stresses in bittersweet (Solanum dulcamara L.).

    PubMed

    Visser, E J W; Zhang, Q; De Gruyter, F; Martens, S; Huber, H

    2016-01-01

    Plants exposed to environmental stress often respond by a change in their phenotypic traits. These changes in trait expression may alleviate the negative effect of such stress factors. However, if multiple stresses are present, responses are likely to be less predictable and hence do not necessarily correlate to plant performance. This study tested if this expectation was true, by subjecting Solanum dulcamara plants to various simultaneous stress factors. Plants were grown in well-watered conditions, drought or flooding, and exposed to either full light or shade for 4 weeks. Shoot and root biomass, stem morphological parameters, such as height, number of nodes and length of stem internodes, and leaf traits like length, specific leaf area, chlorophyll content and stomatal conductance were determined. Both variation in light and in water availability typically caused slower growth, and resulted in distinct phenotypic changes in stem, leaf and root traits. However, effects of stresses on the expression of traits were not always additive. Instead, some combined stress responses (e.g. leaf size) appeared to be limited by physical or physiological constraints, whereas other responses were opposite to each other (e.g. root:shoot ratio), resulting in an intermediate phenotype in the combined stress treatment. These data suggest that in natural conditions, where combined stress factors are likely to be present, the optimal phenotype may not necessarily be expressed. Responses of plants to multiple stress factors may therefore not be associated with immediate advantages in terms of increased performance.

  5. Multiple Applications of Sodium Bisulfate to Broiler Litter Affect Ammonia Release and Litter Properties.

    PubMed

    Hunolt, Alicia E; Maguire, Rory O; Ogejo, Jactone A; Badgley, Brian D; Frame, W Hunter; Reiter, Mark S

    2015-11-01

    Ammonia (NH) emissions from animal manures can cause air and water quality problems. Poultry litter treatment (PLT, sodium bisulfate; Jones-Hamilton Co.) is an acidic amendment that is applied to litter in poultry houses to decrease NH emissions, but currently it can only be applied once before birds are placed in the houses. This project analyzed the effect of multiple PLT applications on litter properties and NH release. Volatility chambers were used to compare multiple, single, and no application of PLT to poultry litter, all with and without fresh manure applications. A field component consisted of two commercial broiler houses: one had a single, preflock PLT application, while the other received PLT reapplications during the flock using an overhead application system. In the volatility chambers, single and reapplied PLT caused greater litter moisture and lower litter pH and , relative to no PLT. After 14 d, NH released from litter treated with reapplied PLT was significantly less than litter with both single and no applications. Furthermore, total N in litter was greatest in litter treated with reapplied PLT, increasing its fertilizer value. In the commercial poultry houses, PLT reapplication led to a temporary decrease in litter pH and , but these effects did not last because of continued bird excretion. Although one preflock PLT application is currently used as a successful strategy to control NH during early flock growth, repeat PLT application using the overhead reapplication system was not successful because of problems with the reapplication system and litter moisture concerns. PMID:26641342

  6. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    PubMed

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

  7. Genetic counselling in multiple sclerosis: risks to sibs and children of affected individuals.

    PubMed

    Sadovnick, A D; Dircks, A; Ebers, G C

    1999-08-01

    Genetic factors are recognized as having important roles in both the overall etiology and the familial aggregation of multiple sclerosis (MS), leading to increased requests for genetic counselling. This paper is designed to provide familial risk data in a practical format for use during genetic counselling for MS. Depending on the amount of genetic sharing among family members, the relative risk of MS compared with that for the general population can range from 1 (adopted sibs and children of the MS proband, with whom they share no genetic material) to 190 (monozygotic co-twins of MS patients, with whom they share 100% of their genetic material). When counselling full sibs of MS patients, risks can be better calculated if information is available on the age of MS onset in the patient and whether or not one parent has MS.

  8. Resveratrol inhibits Epstein Barr Virus lytic cycle in Burkitt's lymphoma cells by affecting multiple molecular targets.

    PubMed

    De Leo, Alessandra; Arena, Giuseppe; Lacanna, Egidio; Oliviero, Giorgio; Colavita, Francesca; Mattia, Elena

    2012-11-01

    Resveratrol (RV), a polyphenolic natural product present in many plants and fruits, exhibits anti-inflammatory, cardio-protective and anti-proliferative properties. Moreover, RV affects a wide variety of viruses including members of the Herpesviridae family, retroviruses, influenza A virus and polyomavirus by altering cellular pathways that affect viral replication itself. Epstein Barr Virus (EBV), the causative agent of infectious mononucleosis, is associated with different proliferative diseases in which it establishes a latent and/or a lytic infection. In this study, we examined the antiviral activity of RV against the EBV replicative cycle and investigated the molecular targets possibly involved. In a cellular context that allows in vitro EBV activation and lytic cycle progression through mechanisms closely resembling those that in vivo initiate and enable productive infection, we found that RV inhibited EBV lytic genes expression and the production of viral particles in a dose-dependent manner. We demonstrated that RV inhibited protein synthesis, decreased reactive oxygen species (ROS) levels, and suppressed the EBV-induced activation of the redox-sensitive transcription factors NF-kB and AP-1. Further insights into the signaling pathways and molecular targets modulated by RV may provide the basis for exploiting the antiviral activity of this natural product on EBV replication.

  9. Decision aids for multiple-decision disease management as affected by weather input errors.

    PubMed

    Pfender, W F; Gent, D H; Mahaffee, W F; Coop, L B; Fox, A D

    2011-06-01

    Many disease management decision support systems (DSSs) 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 management decision recommendations. The extent to which errors in weather inputs affect the quality of the final management outcome depends on a number of aspects of the disease management context, including whether management consists of a single dichotomous decision, or of a multi-decision process extending over the cropping season(s). Decision aids for multi-decision disease management typically are based on simple or complex algorithms of weather data which may be accumulated over several days or weeks. It is difficult to quantify accuracy of multi-decision DSSs due to temporally overlapping disease events, existence of more than one solution to optimizing the outcome, opportunities to take later recourse to modify earlier decisions, and the ongoing, complex decision process in which the DSS is only one component. One approach to assessing importance of weather input errors is to conduct an error analysis in which the DSS outcome from high-quality weather data is compared with that from weather data with various levels of bias and/or variance from the original data. We illustrate this analytical approach for two types of DSS, an infection risk index for hop powdery mildew and a simulation model for grass stem rust. Further exploration of analysis methods is needed to address problems associated with assessing uncertainty in multi-decision DSSs.

  10. 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

  11. 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.

  12. 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…

  13. 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

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

    PubMed

    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 microg/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.

  15. 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.

  16. 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.

  17. Does pain in individuals with multiple sclerosis affect employment? A systematic review and meta-analysis

    PubMed Central

    Shahrbanian, Shahnaz; Auais, Mohammad; Duquette, Pierre; Anderson, Katie; Mayo, Nancy E

    2013-01-01

    BACKGROUND: Individuals with multiple sclerosis (MS) experience some of the highest unemployment rates among all groups of chronic illnesses. Pain has been found to be a common reason for sick leave or early retirement in healthy populations or other groups with chronic illness; however, there is little awareness regarding the effect of pain on the work status of individuals with MS. OBJECTIVES: To estimate the extent to which individuals with pain differ in employment status compared with those without pain among MS patients. METHODS: An extensive systematic review of the scientific literature was performed within the framework of the Cochrane Collaboration to identify studies focusing on the effect of pain on employment in individuals with MS. The following databases were searched: PubMed, EMBASE, PsychInfo, Web of Science, MD Consult and Elsevier, and Science Direct. The methodological quality of studies was assessed using the McMaster Critical Review Form. RESULTS: Ten articles met the inclusion criteria and were included in the systematic review. Of these studies, five that exhibited clinical, methodological and statistical homogeneity were included in the meta-analysis. The between-groups (pain + versus pain −) pooled random OR of being employed was 0.7 (strong), and was significantly different from unity (95% CI 0.5 to 0.9; P=0.001). CONCLUSIONS: The results of the present study indicated that individuals with MS who experience pain were significantly more likely to report a decreased employment rate than individuals with MS who were pain free. PMID:24093124

  18. 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

  19. 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

  20. Consistency, context and confidence in judgements of affective communication in adults with profound intellectual and multiple disabilities.

    PubMed

    Hogg, J; Reeves, D; Roberts, J; Mudford, O C

    2001-02-01

    Twenty-four service providers rated 12 video samples of four service users with whom they were familiar for affective behaviour (i.e. 'like'/'dislike') and confidence (i.e. 'certain'/'uncertain') in their judgement. Each video sample had been recorded as part of a stimulus preference assessment during which a wide range of specific stimuli were presented to each service user. Each video sample was presented twice in a counterbalanced design either with contextual information, i.e. what the presented stimulus was (C) or without such information, i.e. context free (CF). The observers showed considerable individual variation in their judgements, largely uninfluenced by the availability or otherwise of contextual information. However, as a group, observers significantly distinguished between video samples with regard to affective communication (determined through multiple analyses of variance) and the pattern of judgements, i.e. the relative judgement of positive or negative affect, from one sample to another. This showed a good level of consistency between observers (determined through principal components analysis). The impact of contextual information was not apparent for all video samples. However, contextual information significantly influenced judgements in four samples, typically making them more extreme; for example, a response indicative of positive affect in the CF situation became more positive when contextual information was provided, indicating that the stimulus was one that the participant was thought to like.

  1. Consistency, context and confidence in judgements of affective communication in adults with profound intellectual and multiple disabilities.

    PubMed

    Hogg, J; Reeves, D; Roberts, J; Mudford, O C

    2001-02-01

    Twenty-four service providers rated 12 video samples of four service users with whom they were familiar for affective behaviour (i.e. 'like'/'dislike') and confidence (i.e. 'certain'/'uncertain') in their judgement. Each video sample had been recorded as part of a stimulus preference assessment during which a wide range of specific stimuli were presented to each service user. Each video sample was presented twice in a counterbalanced design either with contextual information, i.e. what the presented stimulus was (C) or without such information, i.e. context free (CF). The observers showed considerable individual variation in their judgements, largely uninfluenced by the availability or otherwise of contextual information. However, as a group, observers significantly distinguished between video samples with regard to affective communication (determined through multiple analyses of variance) and the pattern of judgements, i.e. the relative judgement of positive or negative affect, from one sample to another. This showed a good level of consistency between observers (determined through principal components analysis). The impact of contextual information was not apparent for all video samples. However, contextual information significantly influenced judgements in four samples, typically making them more extreme; for example, a response indicative of positive affect in the CF situation became more positive when contextual information was provided, indicating that the stimulus was one that the participant was thought to like. PMID:11168773

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

    PubMed

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

    2011-02-01

    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.

  3. Obesity induced by cafeteria diet disrupts fertility in the rat by affecting multiple ovarian targets.

    PubMed

    Bazzano, M V; Torelli, C; Pustovrh, M C; Paz, D A; Elia, E M

    2015-11-01

    Obesity constitutes a health problem of increasing worldwide prevalence. Among the health detriments caused by obesity, reproduction is disrupted. However, the mechanisms involved in this disruption are not fully understood. Animals fed a cafeteria diet constitute the model for the study of obesity that most closely reflects Western diet habits. The aims of this study were to evaluate whether a cafeteria diet affects ovarian function and to contribute to the understanding of the mechanisms involved. For that purpose, 22-day-old female Wistar rats were fed ad libitum with a standard diet (control group; n = 20) or cafeteria diet (CAF group; n = 20). The cafeteria diet induced obesity and hyperglycaemia, without altering serum triglycerides, cholesterol or C-reactive protein concentrations. This diet also altered ovarian function: the rats showed prolonged dioestrous phases, decreased serum oestradiol concentrations and increased number of antral atretic follicles. Moreover, follicular cysts were detected in the CAF group, concomitantly with a decrease in the number of anti-Müllerian hormone immunoreactive pre-antral follicles and COX-2-positive antral and pre-ovulatory follicles. The authors conclude that a cafeteria diet reduces ovarian reserve, induces the presence of follicular cysts and disturbs the ovulatory process, leading to the delayed pregnancy observed in these animals.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Deletion of exon 8 from the EXT1 gene causes multiple osteochondromas (MO) in a family with three affected members.

    PubMed

    Zhuang, Lei; Gerber, Simon D; Kuchen, Stefan; Villiger, Peter M; Trueb, Beat

    2016-01-01

    Multiple osteochondromas (also called hereditary multiple exostoses) is an autosomal dominant disorder characterized by multiple cartilaginous tumors, which are caused by mutations in the genes for exostosin-1 (EXT1) and exostosin-2 (EXT2). The goal of this study was to elucidate the genetic alterations in a family with three affected members. Isolation of RNA from the patients' blood followed by reverse transcription and PCR amplification of selected fragments showed that the three patients lack a specific region of 90 bp from their EXT1 mRNA. This region corresponds to the sequence of exon 8 from the EXT1 gene. No splice site mutation was found around exon 8. However, long-range PCR amplification of the region from intron 7 to intron 8 indicated that the three patients contain a deletion of 4318 bp, which includes exon 8 and part of the flanking introns. There is evidence that the deletion was caused by non-homologous end joining because the breakpoints are not located within a repetitive element, but contain multiple copies of the deletion hotspot sequence TGRRKM. Exon 8 encodes part of the active site of the EXT1 enzyme, including the DXD signature of all UDP-sugar glycosyltransferases. It is conceivable that the mutant protein exerts a dominant negative effect on the activity of the EXT glycosyltransferase since it might interact with normal copies of the enzyme to form an inactive hetero-oligomeric complex. We suggest that sequencing of RNA might be superior to exome sequencing to detect short deletions of a single exon.

  9. Correct Assembly of RNA Polymerase II Depends on the Foot Domain and Is Required for Multiple Steps of Transcription in Saccharomyces cerevisiae

    PubMed Central

    Garrido-Godino, A. I.; García-López, M. C.

    2013-01-01

    Recent papers have provided insight into the cytoplasmic assembly of RNA polymerase II (RNA pol II) and its transport to the nucleus. However, little is known about the mechanisms governing its nuclear assembly, stability, degradation, and recycling. We demonstrate that the foot of RNA pol II is crucial for the assembly and stability of the complex, by ensuring the correct association of Rpb1 with Rpb6 and of the dimer Rpb4-Rpb7 (Rpb4/7). Mutations at the foot affect the assembly and stability of the enzyme, a defect that is offset by RPB6 overexpression, in coordination with Rpb1 degradation by an Asr1-independent mechanism. Correct assembly is a prerequisite for the proper maintenance of several transcription steps. In fact, assembly defects alter transcriptional activity and the amount of enzyme associated with the genes, affect C-terminal domain (CTD) phosphorylation, interfere with the mRNA-capping machinery, and possibly increase the amount of stalled RNA pol II. In addition, our data show that TATA-binding protein (TBP) occupancy does not correlate with RNA pol II occupancy or transcriptional activity, suggesting a functional relationship between assembly, Mediator, and preinitiation complex (PIC) stability. Finally, our data help clarify the mechanisms governing the assembly and stability of RNA pol II. PMID:23836886

  10. Hardness and elasticity of caries-affected and sound primary tooth dentin bonded with 4-META one-step self-etch adhesives

    PubMed Central

    Hosoya, Yumiko; Tay, Franklin R.; Miyakoshi, Shoichi; Pashley, David H.

    2013-01-01

    Purpose This study evaluated the quality of the interface of sound and carious primary tooth dentin bonded with two 4-META one-step self-etch adhesives. Methods Twelve sound and twelve carious primary molars were bonded with AQ Bond Plus (AQBP; Sun Medical) or Hybrid Bond (HB; Sun Medical) and restored with Clearfil Protect Liner F (Kuraray Medical Inc.). After 24 hours of water immersion, the teeth were sectioned and polished. Resin-dentin interfaces were measured with a nano-indentation tester and hardness and Young’s modulus were calculated. Data were analyzed using one-way or two-ways ANOVA and Fisher’s PLSD test with α=0.05. Resin-dentin interfaces were also observed with SEM and TEM. Ammoniacal silver nitrate was used as a tracer for TEM observation. Results Hardness and Young’s modulus of the interfacial dentin were significantly lower than the underlying intact dentin except for the carious-AQBP group. However, there was no significant difference of hardness and Young's moduli of the interfacial dentin among all groups. TEM revealed extensive interfacial nanoleakage in sound dentin bonded with either AQBP or HB. For the carious teeth, nanoleakage was absent in the hybrid layers bonded with the two adhesives. However, extensive silver deposits were identified from the subsurface, porous caries-affected dentin. PMID:18795517

  11. 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

  12. 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

  13. Direct closure of round skin defects: a four-step technique with multiple subcutaneous and cutaneous "figure-of-8" sutures alleviating dog-ears.

    PubMed

    Tilleman, Tamara Raveh

    2004-12-01

    Excisional biopsies of rounded lesions are performed daily by surgeons. The objective of this article is to establish a surgical technique for direct closure of circular and elliptical defects without the need for additional excision of dog-ears. A four-step technique based on multiple cutaneous and subcutaneous "figure-of-8" sutures is presented. When correctly placed, these sutures can equally distribute the excess tissue along the scar and alleviate dog-ears. The results of the 65 presented cases show that this technique yields short scars and saves healthy skin. A significant reduction of the length-to-width ratio and the arc-to-scar length ratio is obtained. Direct closure of a circular or elliptical defect without stipulating a 3:1 length-to-width ratio is feasible. Among the advantages of the technique are that no excessive healthy tissue is removed and that the scar length is reduced. The long-term outcome is a scar that is thin, linear, flat, and concealed in the body structure. PMID:15577346

  14. Multiple-Step Humidity-Induced Single-Crystal to Single-Crystal Transformations of a Cobalt Phosphonate: Structural and Proton Conductivity Studies.

    PubMed

    Cai, Zhong-Sheng; Bao, Song-Song; Wang, Xi-Zhang; Hu, Zheng; Zheng, Li-Min

    2016-04-01

    Humidity-induced multiple-step single-crystal to single-crystal (SC-SC) transformations are observed in the cobalt phosphonate (NH4)3[Co2(bamdpH)2(HCOO)(H2O)2] (1), where bamdpH4 is (benzylazanediyl)bis(methylene)diphosphonic acid, [C6H5CH2N(CH2PO3H2)2]. Under high-humidity conditions (95% RH), compound 1 experiences hydrolysis at 60 °C which is accompanied by the transformation from a double-chain structure of compound 1 into a single-chain structure of [Co(bamdpH2)(H2O)2]·2H2O (2). When the humidity is below 10% RH, part of the lattice water in compound 2 can be released, forming a third phase, [Co(bamdpH2)(H2O)2]·H2O (3). The structural transformation processes have been monitored by infrared and proton conductivity measurements.

  15. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring.

    PubMed

    de Pagter, Mirjam S; van Roosmalen, Markus J; Baas, Annette F; Renkens, Ivo; Duran, Karen J; van Binsbergen, Ellen; Tavakoli-Yaraki, Masoumeh; Hochstenbach, Ron; van der Veken, Lars T; Cuppen, Edwin; Kloosterman, Wigard P

    2015-04-01

    Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease.

  16. Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis?

    PubMed Central

    Jongen, Peter Joseph; Wesnes, Keith; van Geel, Björn; Pop, Paul; Schrijver, Hans; Visser, Leo H.; Gilhuis, H. Jacobus; Sinnige, Ludovicus G.; Brands, Augustina M.

    2015-01-01

    In persons with multiple sclerosis (MS) a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting MS (eRRMS) were assessed for self-efficacy (MSSES-18), cognition (CDR System), fatigue (MFIS-5), depressive symptoms (BDI), disease impact (MSIS-29), and disability (EDSS). Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (r= 0.65; P< 0.001), Reaction Time Variability (r= 0.57; P< 0.001), and Speed of Memory (r= 0.53; P< 0.01), and between control self-efficacy and Reaction Time Variability (r= 0.55; P< 0.01). Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy. PMID:26064686

  17. 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.

  18. DL-alpha-difluoromethylarginine inhibits intracellular Trypanosoma cruzi multiplication by affecting cell division but not trypomastigote-amastigote transformation.

    PubMed

    Yakubu, M A; Basso, B; Kierszenbaum, F

    1992-06-01

    DL-alpha-difluoromethylarginine (DFMA), a specific, irreversible inhibitor of arginine decarboxylase (ADC), decreases the capacity of Trypanosoma cruzi to invade and multiply within different types of mammalian host cells in vitro. In this work we found that inhibition of intracellular growth results from selective impairment of amastigote division without appreciable alteration of the capacity of the invading trypomastigotes to transform into the replicative amastigote form. Addition of agmatine, the product of arginine decarboxylation, reversed the inhibitory effect of DFMA. Inhibition of ornithine decarboxylase activity by DL-alpha-difluoromethylornithine present in the medium prior to and during infection did not affect trypomastigote transformation or amastigote replication and did not change the magnitude of the inhibitory effect of DFMA on parasite multiplication. Hence, neither polyamine synthesis via the ornithine decarboxylase pathway nor salvage of host cell polyamines by T. cruzi appeared to be a likely explanation for the normal rate of parasite transformation that was seen in the presence of DFMA. Two clones of T. cruzi, TMSU-1 and TMSU-2, were tested for their degrees of sensitivity to the inhibitory effects of DFMA. Both trypomastigote association with (i.e., binding to and penetration of) myoblasts, and intracellular amastigote multiplication by either clone were found to be significantly (P less than 0.05) but not completely inhibited by DFMA. Therefore, the partial inhibition of T. cruzi infectivity and replication caused by DFMA is unlikely to represent a composite of effects of the drug on DFMA-sensitive and insensitive clones.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages.

    PubMed Central

    Read, R C; Zimmerli, S; Broaddus, C; Sanan, D A; Stephens, D S; Ernst, J D

    1996-01-01

    Group B Neisseria meningitidis causes systemic disease, including meningitis, after initial colonization and subsequent penetration of nasopharyngeal mucosa, a tissue which is richly populated by macrophages. In an initial effort to characterize the interaction of N. meningitidis and mature human macrophages, the influence of the alpha2-->8) -linked polysialic acid capsule on the interaction of N. meningitidis with human monocyte-derived macrophages was investigated with a capsulate case isolate and an isogenic Tn916-derived noncapsulate transformant. The capsulate strain was fourfold less adherent to the macrophage surface after cold incubation, although adherence of both strains was significantly increased after opsonization with nonimmune C5-depleted serum. When opsonized inocula were adjusted so that they adhered to macrophages in equal numbers, the two strains were internalized at equivalent rates and both entered membrane-bound compartments (phagosomes). Colocalization of bacteria with the late endosomal and lysosomal marker lysosome-associated membrane protein revealed that fusion of lysosomes with phagosomes containing the capsulate organism was significantly reduced 10 and 30 min after entry, but by 1 h, no difference between the strains was observed. Once internalized, meningococci were effectively killed, although more rapid killing of the capsulate strain was observed over the first 3 h. These results indicate that the (alpha2-->8)-linked polysialic acid capsule modifies the interaction of meningococci with human macrophages at multiple steps, including adherence to the macrophage surface and phagosome-lysosome fusion. Moreover, the discordance between the kinetics of phagosome- lysosome fusion and bacterial killing suggests that a nonlysosomal mechanism may be responsible for a significant fraction of macrophage killing of N. meningitidis. PMID:8757855

  20. 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

  1. 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 ...

  2. The Drosophila Transcription Factor Dimmed Affects Neuronal Growth and Differentiation in Multiple Ways Depending on Neuron Type and Developmental Stage

    PubMed Central

    Liu, Yiting; Luo, Jiangnan; Nässel, Dick R.

    2016-01-01

    Growth of postmitotic neurons occurs during different stages of development, including metamorphosis, and may also be part of neuronal plasticity and regeneration. Recently we showed that growth of post-mitotic neuroendocrine cells expressing the basic helix loop helix (bHLH) transcription factor Dimmed (Dimm) in Drosophila could be regulated by insulin/IGF signaling and the insulin receptor (dInR). Dimm is also known to confer a secretory phenotype to neuroendocrine cells and can be part of a combinatorial code specifying terminal differentiation in peptidergic neurons. To further understand the mechanisms of Dimm function we ectopically expressed Dimm or Dimm together with dInR in a wide range of Dimm positive and Dimm negative peptidergic neurons, sensory neurons, interneurons, motor neurons, and gut endocrine cells. We provide further evidence that dInR mediated cell growth occurs in a Dimm dependent manner and that one source of insulin-like peptide (DILP) for dInR mediated cell growth in the CNS is DILP6 from glial cells. Expressing both Dimm and dInR in Dimm negative neurons induced growth of cell bodies, whereas dInR alone did not. We also found that Dimm alone can regulate cell growth depending on specific cell type. This may be explained by the finding that the dInR is a direct target of Dimm. Conditional gene targeting experiments showed that Dimm alone could affect cell growth in certain neuron types during metamorphosis or in the adult stage. Another important finding was that ectopic Dimm inhibits apoptosis of several types of neurons normally destined for programmed cell death (PCD). Taken together our results suggest that Dimm plays multiple transcriptional roles at different developmental stages in a cell type-specific manner. In some cell types ectopic Dimm may act together with resident combinatorial code transcription factors and affect terminal differentiation, as well as act in transcriptional networks that participate in long term maintenance

  3. 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

  4. 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

  5. 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.

  6. Estimation of triggered-lightning dart-stepped-leader currents from close multiple-station dE/dt pulse measurements

    NASA Astrophysics Data System (ADS)

    Gamerota, W. R.; Uman, M. A.; Hill, J. D.; Ngin, T.; Pilkey, J.; Jordan, D. M.

    2015-02-01

    The modified transmission line model is used to derive the vertically propagating leader-step currents necessary to radiate measured dart-stepped-leader dE/dt pulses from triggered lightning at close range (<400 m) and low altitude (<70 m). The model-predicted dE/dt pulses were compared with measured dE/dt pulses at nine locations ranging from 27 to 391 m from the channel base for four dE/dt pulses radiated from two triggered dart-stepped leaders. The dE/dt pulses at the closest station, 27 m, were unipolar, dominated by electrostatic and induction components of the radiated dE/dt, and of opposite polarity to the more distant initial dE/dt peaks. The other, more distant, eight stations exhibited bipolar dE/dt pulses, being more or less dominated by the dE/dt radiation component. The derived leader-step current has a slow front that precedes a fast transition to peak amplitude followed by a slow decay to zero after several microseconds. For the four modeled dE/dt pulses, the estimated causative leader-step current peak amplitudes varied from 0.9 to 1.8 kA, the half-peak widths ranged from 370 to 560 ns, the charge transfers were about 1 mC, and the peak current derivatives were about 10 kA/µs. The upward propagation speeds of the leader-step current were from 1.1 to 1.5 × 108 m/s with exponential spatial current decay constants from 13 to 27 m. One dE/dt pulse is analyzed in more detail by studying changes in model-predicted waveforms versus current initiation altitude and by examining the effect of varying model input parameters.

  7. A big first step.

    PubMed

    Jones, Howard W

    2004-11-01

    The singleton, term gestation, live birth rate per cycle initiated (BESST) endpoint proposed at the beginning of 2004 is a first big step which should be added to by the consideration of multiple pregnancy rates in relation to singleton rates, by recording of fetal reductions and of pregnancies resulting from cryopreserved material. After three or more steps we may have an accurate reporting system which helps patients to distinguish the pros and cons for singleton term delivery. PMID:15479704

  8. 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.

  9. 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.

  10. 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…

  11. Multiple minute digitate hyperkeratosis affecting the face and folds: clinical, dermoscopic, and histological report of a familial case.

    PubMed

    Correia, Osvaldo; Rocha, Natividade; Haneke, Eckart

    2014-01-01

    A case of a generalized non-follicular digitate keratosis classified as multiple minute digitate hyperkeratosis is described with suggestive clinical, dermoscopic, and histopathogical data. The patient was a 52-year-old Caucasian woman presenting a 6-year history of multiple asymptomatic skin-colored digitate lesions, 3 to 5 mm long and 1 to 2 mm wide, distributed on the forehead, neck, and extensor surface of the arms as well as in the inframammary folds, axillae, and lower limbs, especially on the popliteal fold. She reported having a 67-year-old sister and a 39-year-old niece with an identical eruption. Treatment with 15% glycolic acid (AHA) lotion and heliotherapy improved this disturbing eruption.

  12. 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

  13. Dynamic and structural characterisation of multiple steps during complex formation between E. coli RNA polymerase and the tetR promoter from pSC101.

    PubMed Central

    Duval-Valentin, G; Ehrlich, R

    1987-01-01

    Kinetic, functional and structural studies of the recognition of the tetR promoter from pSC101 by E. coli RNA polymerase allowed the characterization of several steps in the specific complex formation and transcription initiation process. First, enzyme and DNA enter in a short life-time complex. An isomerization will convert this unstable complex into a closed stable one where RNA polymerase is tightly attached without establishing stable chemical contacts with the bases. In the next step, stable close contacts appear between both macromolecules involving mainly the downstream part of the promoter. A further isomerization will lead to an open complex where DNA is locally melted and the system is able to initiate transcription. This latter process is accompanied by changes in the upstream part of the promoter. Finally, in vitro transcription assays showed that the position of the major transcription start sites depends on temperature. From the reported results, it appears that the recognition event is a sequential process where different structural elements of the promoter, that can be located apart in the sequence, are involved in a concerted manner in each stage. Images PMID:3547327

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

    PubMed

    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

    2013-11-01

    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.

  15. 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

  16. 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

  17. 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

  18. Step bunching and ordering induced by step-edge barriers

    NASA Astrophysics Data System (ADS)

    Zhao, Yuegang; Liu, Feng; Tersoff, Jerry; Lagally, Max G.

    2000-03-01

    We derive the equation of motion of steps for step flow growth under the influence of both misfit strain and step-edge barriers. An energy barrier at a step for an atom arriving from the lower terrace causes a step bunching instability. Simulation results show that the bunching is predominantly driven by a coalescence mechanism, leading to multiple transient stages of metastable step bunch arrays, with average bunch size of 2, 4, and 8 steps. The bunch array in these transient stages exhibits a surprisingly good long-range order. Similar kinetic step-bunch ordering has been seen in a a recent experiment[1]. Reference: [1]: C. Schelling, G. Springholz, and F. Schäffler, Phys. Rev. Letts, 83(995)1999.

  19. 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.

  20. 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

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

    PubMed Central

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

    2016-01-01

    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 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

  2. 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

  3. Characterization Of A Multiple-Step In-Situ Plasma Enhanced Chemical Vapor Deposition (PECVD) Tetraethylorthosilicate (TEOS) Planarization Scheme For Submicron Manufacturing

    NASA Astrophysics Data System (ADS)

    Perchard, Jeannine M.; Smith, Howard E.; O'Connor, Robert; Olsen, Jeff; Law, Kam

    1990-02-01

    This paper presents a manufacturable process to deposit dielectric films capable of void-free filling of submicron spaces between adjacent interconnect lines as well as local planarization of topography using conformal TEOS-based oxides and in-situ etch processes. The deposition planarization process is user programmable and is accomplished entirely in a single multi-chamber system (Applied Materials Precision 5000) in one cassette-to-cassette operation. Data on the step coverage and topographic gap filling characteristics of the TEOS oxide deposition and etchback sequences are presented. Analyses of material properties and the electrical stability of the TEOS-based oxide films deposited in this system indicate that the films are suitable for interlevel dielectric applications in submicron devices. Film properties such as stress, thermal shrinkage, density, moisture absorption, and dopant incorporation were characterized for the two types of low temperature TEOS-based oxides used in the process, and these are compared to the properties of low temperature SiH4-based LPCVD oxides. The results show that the TEOS films compare favorably to the "industry standard" SiH4-based films. SIMS analysis was used to investigate the purity of the TEOS oxides. The signals of aluminum, iron, and other trace metals were at or below their detection limits, for both the PE-TEOS and the thermal ozone-TEOS oxides. The carbon content of the PE-TEOS film was 0.8 atomic percent while both the thermal ozone-TEOS and the LPCVD SiH4 oxides had less than 0.2 atomic percent. Electrical stability of the composite TEOS oxides was evaluated using bias-temperature stress C-V analysis. Undoped and phosphorus-doped PE-TEOS oxides produced lower Hatband voltage changes than the reference LPCVD SiH4 oxides. The undoped PE-TEOS films were found to have mobile ion charge densities of 7.7*109 cm-2, compared with the LPCVD SiH4 oxide values of 1.2*1011 cm -2. Device level electrical testing of devices

  4. 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.

  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. Differential Regulation of Multiple Steps in Inositol 1,4,5-Trisphosphate Signaling by Protein Kinase C Shapes Hormone-stimulated Ca2+ Oscillations.

    PubMed

    Bartlett, Paula J; Metzger, Walson; Gaspers, Lawrence D; Thomas, Andrew P

    2015-07-24

    How Ca(2+) oscillations are generated and fine-tuned to yield versatile downstream responses remains to be elucidated. In hepatocytes, G protein-coupled receptor-linked Ca(2+) oscillations report signal strength via frequency, whereas Ca(2+) spike amplitude and wave velocity remain constant. IP3 uncaging also triggers oscillatory Ca(2+) release, but, in contrast to hormones, Ca(2+) spike amplitude, width, and wave velocity were dependent on [IP3] and were not perturbed by phospholipase C (PLC) inhibition. These data indicate that oscillations elicited by IP3 uncaging are driven by the biphasic regulation of the IP3 receptor by Ca(2+), and, unlike hormone-dependent responses, do not require PLC. Removal of extracellular Ca(2+) did not perturb Ca(2+) oscillations elicited by IP3 uncaging, indicating that reloading of endoplasmic reticulum stores via plasma membrane Ca(2+) influx does not entrain the signal. Activation and inhibition of PKC attenuated hormone-induced Ca(2+) oscillations but had no effect on Ca(2+) increases induced by uncaging IP3. Importantly, PKC activation and inhibition differentially affected Ca(2+) spike frequencies and kinetics. PKC activation amplifies negative feedback loops at the level of G protein-coupled receptor PLC activity and/or IP3 metabolism to attenuate IP3 levels and suppress the generation of Ca(2+) oscillations. Inhibition of PKC relieves negative feedback regulation of IP3 accumulation and, thereby, shifts Ca(2+) oscillations toward sustained responses or dramatically prolonged spikes. PKC down-regulation attenuates phenylephrine-induced Ca(2+) wave velocity, whereas responses to IP3 uncaging are enhanced. The ability to assess Ca(2+) responses in the absence of PLC activity indicates that IP3 receptor modulation by PKC regulates Ca(2+) release and wave velocity.

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

    PubMed

    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

  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. Nicotiana attenuata SIPK, WIPK, NPR1, and Fatty Acid-Amino Acid Conjugates Participate in the Induction of Jasmonic Acid Biosynthesis by Affecting Early Enzymatic Steps in the Pathway1[W][OA

    PubMed Central

    Kallenbach, Mario; Alagna, Fiammetta; Baldwin, Ian Thomas; Bonaventure, Gustavo

    2010-01-01

    Wounding and herbivore attack elicit the rapid (within minutes) accumulation of jasmonic acid (JA) that results from the activation of previously synthesized biosynthetic enzymes. Recently, several regulatory factors that affect JA production have been identified; however, how these regulators affect JA biosynthesis remains at present unknown. Here we demonstrate that Nicotiana attenuata salicylate-induced protein kinase (SIPK), wound-induced protein kinase (WIPK), nonexpressor of PR-1 (NPR1), and the insect elicitor N-linolenoyl-glucose (18:3-Glu) participate in mechanisms affecting early enzymatic steps of the JA biosynthesis pathway. Plants silenced in the expression of SIPK and NPR1 were affected in the initial accumulation of 13-hydroperoxy-linolenic acid (13-OOH-18:3) after wounding and 18:3-Glu elicitation by mechanisms independent of changes in 13-lipoxygenase activity. Moreover, 18:3-Glu elicited an enhanced and rapid accumulation of 13-OOH-18:3 that depended partially on SIPK and NPR1 but was independent of increased 13-lipoxygenase activity. Together, the results suggested that substrate supply for JA production was altered by 18:3-Glu elicitation and SIPK- and NPR1-mediated mechanisms. Consistent with a regulation at the level of substrate supply, we demonstrated by virus-induced gene silencing that a wound-repressed plastidial glycerolipase (NaGLA1) plays an essential role in the induction of de novo JA biosynthesis. In contrast to SIPK and NPR1, mechanisms mediated by WIPK did not affect the production of 13-OOH-18:3 but were critical to control the conversion of this precursor into 12-oxo-phytodienoic acid. These differences could be partially accounted for by reduced allene oxide synthase activity in WIPK-silenced plants. PMID:19897603

  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. 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.

  13. The Arabidopsis gene DIG6 encodes a large 60S subunit nuclear export GTPase 1 that is involved in ribosome biogenesis and affects multiple auxin-regulated development processes.

    PubMed

    Zhao, Huayan; Lü, Shiyou; Li, Ruixi; Chen, Tao; Zhang, Huoming; Cui, Peng; Ding, Feng; Liu, Pei; Wang, Guangchao; Xia, Yiji; Running, Mark P; Xiong, Liming

    2015-11-01

    The circularly permuted GTPase large subunit GTPase 1 (LSG1) is involved in the maturation step of the 60S ribosome and is essential for cell viability in yeast. Here, an Arabidopsis mutant dig6 (drought inhibited growth of lateral roots) was isolated. The mutant exhibited multiple auxin-related phenotypes, which included reduced lateral root number, altered leaf veins, and shorter roots. Genetic mapping combined with next-generation DNA sequencing identified that the mutation occurred in AtLSG1-2. This gene was highly expressed in regions of auxin accumulation. Ribosome profiling revealed that a loss of function of AtLSG1-2 led to decreased levels of monosomes, further demonstrating its role in ribosome biogenesis. Quantitative proteomics showed that the expression of certain proteins involved in ribosome biogenesis was differentially regulated, indicating that ribosome biogenesis processes were impaired in the mutant. Further investigations showed that an AtLSG1-2 deficiency caused the alteration of auxin distribution, response, and transport in plants. It is concluded that AtLSG1-2 is integral to ribosome biogenesis, consequently affecting auxin homeostasis and plant development.

  14. 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

  15. 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.

  16. 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.

  17. Multiple genetic alterations in human carcinogenesis.

    PubMed Central

    Sugimura, T; Terada, M; Yokota, J; Hirohashi, S; Wakabayashi, K

    1992-01-01

    Cancer development in man appeared to be a multistage process as suggested by epidemiological studies on commonly occurring gastric, colon, and breast cancers and also on human retrovirus-related leukemia, and by the finding by physicians and surgeons of precancerous lesions for many types of neoplasias. In the last 10 years it has become evident that human cancers have multiple genetic alterations caused by point mutations, recombinations, amplifications, and/or deletions. The genes affected include both oncogenes and tumor-suppressor genes and genes that accelerate cell proliferation and metastasis. Cancers with more malignant properties and poorer prognosis are generally associated with larger numbers of genetic alterations. These multiple genetic alterations are considered to be a direct reflection of the multiple steps involved in carcinogenesis. The multiple genetic alterations are caused by multiple environmental carcinogenic substances or factors, each of which usually exists only at minute concentrations and does not exert any major impact alone except under particular occupational, iatrogenic, and locally geographic conditions. The fact that carcinogenesis is a multistep process involving multiple genetic alterations clearly needs to be taken into consideration in assessing the risks of environmental carcinogenic substances or factors. The increasing incidence of multiple primary cancers is also most easily understood from the viewpoint of multiple steps in carcinogenesis. Possible multiple approaches to cancer prevention should therefore be considered in relation to multistep carcinogenesis and multiple carcinogenic factors. PMID:1486862

  18. Factors affecting spontaneous reduction of corpora lutea and twin embryos during the late embryonic/early fetal period in multiple-ovulating dairy cows.

    PubMed

    López-Gatius, F; García-Ispierto, I; Hunter, R H F

    2010-02-01

    Spontaneous reduction of advanced twin embryos has been described in high-producing, Holstein-Fresian (Bos taurus) dairy herds. The first objective of the current study was to determine whether management and cow factors could have an effect on such a reduction in twin pregnancies during the early fetal period. Because loss of a corpus luteum was noted in cows suffering twin reduction, we expanded our study to include multiple-ovulating cows carrying singletons. Pregnancy was diagnosed and confirmed from Days 28 to 34 and 56 to 62 postinsemination. Sixty-nine (23.5%) of 293 pregnant cows with two corpora lutea carrying singletons and 132 (28.4%) of 464 twin pregnancies recorded on first pregnancy diagnosis subsequently lost one of the corpora lutea or one of the embryos, respectively. Thirty-four (25.8%) of the 132 twin pregnancies suffering embryo reduction lost one corpus luteum along with the embryo. Corpus luteum reduction always occurred in the ovary ipsilateral to the gravid horn suffering embryo reduction. Binary logistic regressions were performed considering corpus luteum and embryo reduction as dependent variables in single and twin pregnancies, respectively, and several management- and cow-related factors as independent variables. In cows carrying singletons, the risk of corpus luteum reduction was 14.3 (1/0.07) times lower for a given herd, whereas the interaction season by laterality significantly affected corpus luteum reduction such that in cows with two corpora lutea ipsilateral to the horn of pregnancy, the risk of reduction decreased during the winter period. In cows carrying twins, ipsilateral twin pregnancies were 3.45 (1/0.29) times more likely to undergo the loss of one embryo than bilateral twin pregnancies. As an overall conclusion, both corpora lutea and embryos were vulnerable to the effects of stress factors during the early fetal period in cows maintaining their pregnancies. A strong unilateral relationship between the corpus luteum and

  19. Terrace-width distributions of touching steps: Modification of the fermion analogy with implications for measuring step-step interactions

    NASA Astrophysics Data System (ADS)

    Sathiyanarayanan, Rajesh; Hamouda, Ajmi Bh.; Einstein, T. L.

    2009-10-01

    Using Monte Carlo simulations, we compute the terrace-width distributions (TWDs) of surfaces in which steps can touch each other, forming multiple-atomic height steps, but cannot cross (no overhangs), and so inconsistent with the standard mapping to spinless fermions. Our results show that the generalized Wigner distribution with minor modifications at small step separations, gives a very good fit for TWDs of touching steps. The interaction strength derived from the fit parameter (ϱ) indicates an effective attraction between steps. The strength of this effective attraction decreases for larger mean-step separations and decreasing step-touching energies; describable via finite-size scaling. Hence, accurate extraction of the true repulsion strength requires multiple vicinalities.

  20. 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

  1. Steps to Maturity Program. Evaluation.

    ERIC Educational Resources Information Center

    Nanaimo School District #68 (British Columbia).

    In fall 1989, the Nanaimo (British Columbia) School District No. 68 asked five people, selected from the school system and community, to evaluate the "Steps to Maturity" Program (STMP), a district-wide family life education and affective development program that has developed gradually since 1972. The evaluation team interviewed a large number of…

  2. 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.

  3. 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.

  4. Step-Growth Polymerization.

    ERIC Educational Resources Information Center

    Stille, J. K.

    1981-01-01

    Following a comparison of chain-growth and step-growth polymerization, focuses on the latter process by describing requirements for high molecular weight, step-growth polymerization kinetics, synthesis and molecular weight distribution of some linear step-growth polymers, and three-dimensional network step-growth polymers. (JN)

  5. 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

  6. National Multiple Sclerosis Society

    MedlinePlus

    ... Join the Community Stay Informed Corporate Support National Multiple Sclerosis Society Our Mission: People affected by MS can ... 10.5 Million in New Research to Stop Multiple Sclerosis, Restore Function and End MS Forever October 11, ...

  7. Step by Step: Avoiding Spiritual Bypass in 12-Step Work

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Clarke, Philip B.; Graves, Elizabeth G.

    2009-01-01

    With spirituality as a cornerstone, 12-step groups serve a vital role in the recovery community. It is important for counselors to be mindful, however, of the potential for clients to be in spiritual bypass, which likely will undermine the recovery process.

  8. 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

  9. A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh.

    PubMed

    Hyder, S M Ziauddin; Haseen, Farhana; Khan, Marufa; Schaetzel, Tom; Jalal, Chowdhury S B; Rahman, Mizanur; Lönnerdal, Bo; Mannar, Venkatesh; Mehansho, Haile

    2007-09-01

    Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies. The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin (Hb) concentrations, micronutrient status, and growth among adolescent girls in rural Bangladesh. A total of 1125 girls (Hb > or = 70 g/L) enrolled in a randomized, double-blind, placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance. The beverage was provided at schools 6 d/wk for 12 mo. Concentrations of Hb and serum ferritin (sFt), retinol, zinc, and C-reactive protein were measured in venous blood samples at baseline, 6 mo, and 12 mo. In addition, weight, height, and mid-upper arm circumference (MUAC) measurements were taken. The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo (P < 0.01). Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia (Hb <120 g/L), iron deficiency (sFt <12 microg/L), and low serum retinol concentrations (serum retinol <0.70 micromol/L) (OR = 2.04, 5.38, and 5.47, respectively; P < 0.01). The fortified beverage group had greater increases in weight, MUAC, and BMI over 6 mo (P < 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the sFt level continued to increase (P = 0.01). The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh.

  10. 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

  11. 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.

  12. 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) ...

  13. 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.

  14. Targeted Deep Sequencing in Multiple-Affected Sibships of European Ancestry Identifies Rare Deleterious Variants in PTPN22 That Confer Risk for Type 1 Diabetes.

    PubMed

    Ge, Yan; Onengut-Gumuscu, Suna; Quinlan, Aaron R; Mackey, Aaron J; Wright, Jocyndra A; Buckner, Jane H; Habib, Tania; Rich, Stephen S; Concannon, Patrick

    2016-03-01

    Despite finding more than 40 risk loci for type 1 diabetes (T1D), the causative variants and genes remain largely unknown. Here, we sought to identify rare deleterious variants of moderate-to-large effects contributing to T1D. We deeply sequenced 301 protein-coding genes located in 49 previously reported T1D risk loci in 70 T1D cases of European ancestry. These cases were selected from putatively high-risk families that had three or more siblings diagnosed with T1D at early ages. A cluster of rare deleterious variants in PTPN22 was identified, including two novel frameshift mutations (ss538819444 and rs371865329) and two missense variants (rs74163663 and rs56048322). Genotyping in 3,609 T1D families showed that rs56048322 was significantly associated with T1D and that this association was independent of the T1D-associated common variant rs2476601. The risk allele at rs56048322 affects splicing of PTPN22, resulting in the production of two alternative PTPN22 transcripts and a novel isoform of LYP (the protein encoded by PTPN22). This isoform competes with the wild-type LYP for binding to CSK and results in hyporesponsiveness of CD4(+) T cells to antigen stimulation in T1D subjects. These findings demonstrate that in addition to common variants, rare deleterious variants in PTPN22 exist and can affect T1D risk.

  15. 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

  16. Stem cell factor potentiates histamine secretion by multiple mechanisms, but does not affect tumour necrosis factor-alpha release from rat mast cells.

    PubMed Central

    Lin, T J; Bissonnette, E Y; Hirsh, A; Befus, A D

    1996-01-01

    The effect of stem cell factor (SCF) on histamine and tumour necrosis factor-alpha (TNF-alpha) release from rat peritoneal mast cells (PMC) was determined and the intracellular pathways involved in the potentiation of histamine secretion were investigated. The effects of SCF (2-100 ng/ml) were examined following both short-term (0 and 20 min) and long-term (up to 24hr) preincubations with SCF. Pretreatment of PMC with SCF for 0 min (concurrent) or 20 min did not induce histamine secretion directly, but significantly increased antigen (Ag)-induced histamine secretion. SCF potentiated Ag-induced intracellular Ca2+ increase and calcium ionophore A23187-induced histamine secretion. Pertussis toxin (PT) inhibited SCF-induced potentiation of IgE-dependent histamine secretion, indicating that PT-sensitive G-proteins are involved in the immediate effects of SCF. In long-term incubation experiments, SCF pretreatment for 18-24 hr significantly enhanced Ag-induced histamine secretion, but did not affect Ag-induced intracellular Ca2+ levels. The effects of long-term incubation with SCF, but not the short-term effects, were blocked by cycloheximide. Interestingly, spontaneous and Ag-induced TNF-alpha release from rat PMC were not affected by pretreatment with SCF (2-500 ng/ml) for 1 to 24 hr. Thus, through immediate and delayed mechanisms, SCF potentiates histamine release from PMC, but has not effect on TNF-alpha release. The regulation of MC by SCF may be important in allergic and other inflammatory diseases. PMID:8943730

  17. Non-random autosome segregation: a stepping stone for the evolution of sex chromosome complexes? Sex-biased transmission of autosomes could facilitate the spread of antagonistic alleles, and generate sex-chromosome systems with multiple X or Y chromosomes.

    PubMed

    Schwander, Tanja; Beukeboom, Leo W

    2011-02-01

    A new study in Caenorhabditis elegans shows that homologous autosomes segregate non-randomly with the sex chromosome in the heterogametic sex. Segregation occurs according to size, small autosomes segregating with, and large autosomes segregating away from the X-chromosome. Such sex-biased transmission of autosomes could facilitate the spread of sexually antagonistic alleles whose effects favor the fitness of one sex at the expense of the other. This may provide a first step toward the evolution of new sex determination systems.

  18. 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

  19. Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements.

    PubMed

    D'Souza, I; Poorkaj, P; Hong, M; Nochlin, D; Lee, V M; Bird, T D; Schellenberg, G D

    1999-05-11

    Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17) is caused by mutations in the tau gene, and the signature lesions of FTDP-17 are filamentous tau inclusions. Tau mutations may be pathogenic either by altering protein function or gene regulation. Here we show that missense, silent, and intronic tau mutations can increase or decrease splicing of tau exon 10 (E10) by acting on 3 different cis-acting regulatory elements. These elements include an exon splicing enhancer that can either be strengthened (mutation N279(K)) or destroyed (mutation Delta280(K)), resulting in either constitutive E10 inclusion or the exclusion of E10 from tau transcripts. E10 contains a second regulatory element that is an exon splicing silencer, the function of which is abolished by a silent FTDP-17 mutation (L284(L)), resulting in excess E10 inclusion. A third element inhibiting E10 splicing is contained in the intronic sequences directly flanking the 5' splice site of E10 and intronic FTDP-17 mutations in this element enhance E10 inclusion. Thus, tau mutations cause FTDP-17 by multiple pathological mechanisms, which may explain the phenotypic heterogeneity observed in FTDP-17, as exemplified by an unusual family described here with tau pathology as well as amyloid and neuritic plaques.

  20. Relationship between the weight-bearing ratio on the affected lower extremity and gait ability using a portable electronic foot sensor shoe (Step Aid(®)) in hemiplegic stroke patients.

    PubMed

    Itotani, Keisuke; Murakami, Masahito; Itotani, Motoko; Nagai, Atsushi; Imabori, Yuzo; Fujimoto, Kazuyuki; Tanaka, Mamoru; Kato, Junichi

    2015-02-01

    [Purpose] This study investigated the association between the weight-bearing ratio (WBR) and gait ability of a paretic lower limb while walking using a shoe-type load-measuring apparatus. [Subjects] The Subjects comprised 17 stroke patients who were classified into the following two groups: the independent walking group, and the non-independent walking group. [Methods] The 10-m walking time (inside and outside parallel bars) and the Berg Balance Scale (BBS) were measured. The WBR of the paretic lower limb was measured during static standing and while walking inside and outside parallel bars, and the coefficient of variation (CV) was calculated. WBR was evaluated using the Step Aid. [Results] The BBS and WBR were significantly decreased in the non-independent walking group, while the 10-m walking time and the CV were significantly increased in the non-independent walking group. [Conclusion] The CV and WBR of a paretic lower limb while walking appear to be important indices of achievement of independent gait in hemiplegic stroke patients, and they may be used in gait rehabilitation for diseases requiring weight-bearing training to follow the course of training using a shoe-type load-measuring apparatus.

  1. 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

  2. An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions.

    PubMed

    Kim, Bum Jun; Zaveri, Hitisha P; Shchelochkov, Oleg A; Yu, Zhiyin; Hernández-García, Andrés; Seymour, Michelle L; Oghalai, John S; Pereira, Fred A; Stockton, David W; Justice, Monica J; Lee, Brendan; Scott, Daryl A

    2013-01-01

    Individuals with terminal and interstitial deletions of chromosome 1p36 have a spectrum of defects that includes eye anomalies, postnatal growth deficiency, structural brain anomalies, seizures, cognitive impairment, delayed motor development, behavior problems, hearing loss, cardiovascular malformations, cardiomyopathy, and renal anomalies. The proximal 1p36 genes that contribute to these defects have not been clearly delineated. The arginine-glutamic acid dipeptide (RE) repeats gene (RERE) is located in this region and encodes a nuclear receptor coregulator that plays a critical role in embryonic development as a positive regulator of retinoic acid signaling. Rere-null mice die of cardiac failure between E9.5 and E11.5. This limits their usefulness in studying the role of RERE in the latter stages of development and into adulthood. To overcome this limitation, we created an allelic series of RERE-deficient mice using an Rere-null allele, om, and a novel hypomorphic Rere allele, eyes3 (c.578T>C, p.Val193Ala), which we identified in an N-ethyl-N-nitrosourea (ENU)-based screen for autosomal recessive phenotypes. Analyses of these mice revealed microphthalmia, postnatal growth deficiency, brain hypoplasia, decreased numbers of neuronal nuclear antigen (NeuN)-positive hippocampal neurons, hearing loss, cardiovascular malformations-aortic arch anomalies, double outlet right ventricle, and transposition of the great arteries, and perimembranous ventricular septal defects-spontaneous development of cardiac fibrosis and renal agenesis. These findings suggest that RERE plays a critical role in the development and function of multiple organs including the eye, brain, inner ear, heart and kidney. It follows that haploinsufficiency of RERE may contribute-alone or in conjunction with other genetic, environmental, or stochastic factors-to the development of many of the phenotypes seen in individuals with terminal and interstitial deletions that include the proximal region of

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Construction of the Vinalhaven Intrusive Complex, Maine, USA: the Plutonic Record of Evolving Magma Chambers Affected by Multiple Episodes of Replenishment, Rejuvenation, Crystal Accumulation and Eruption

    NASA Astrophysics Data System (ADS)

    Wiebe, R. A.; Hawkins, D. P.

    2004-12-01

    Increasingly, the plutonic roots of volcanic systems can be shown to contain temporal records of events inferred from the study of volcanic rocks. The Vinalhaven intrusive complex preserves evidence for multiple episodes of silicic and mafic replenishments, rejuvenation of granite, and probable eruptive events over a nominal time-span of 1.7 Ma (Hawkins and Wiebe, this volume). The complex is about 12 km in diameter and consists mainly of cg granite, a thick section of arcuate, inward-dipping gabbro-diorite sheets in the southeastern half of the complex, and a circular core of fg granite. Field relations demonstrate that the base of the intrusion is along the southeastern margin of the complex, and the top is along the northwestern margin where it intrudes coeval volcanic rocks. Aphyric basaltic and granitic dikes fed this essentially bimodal intrusion. When basaltic dikes intersected a silicic chamber, basalt spread across a floor of silicic crystal mush to form gabbro-diorite sheets in granite. Several extensive layers of angular blocks of country rock occur within the mafic rocks. Granitic dikes and the fg granitic core of the complex have sharp to gradational contacts with cg granite, and, locally, both granites are intimately mixed and commingled. These relations indicate that new silicic injections mixed into partly crystallized resident magma. Several irregular bodies of porphyry (0.2 to 0.5 km in average dimension) intrude cg granite with sharp, gradational, or commingled contacts. The porphyry has 5 to 40% corroded phenocrysts, identical in composition to crystals in the granite, and a variably quenched matrix. Some of these bodies formed when late injections of basalt remelted largely solid portions of cg granite. New silicic input may have contributed to other porphyry bodies. The matrix probably quenched because of a sudden decrease in pressure, possibly due to eruption of magma from the chamber. The cg granite and inter-layered mafic rocks preserve a

  8. Detection of Steps in Single Molecule Data

    PubMed Central

    Aggarwal, Tanuj; Materassi, Donatello; Davison, Robert; Hays, Thomas; Salapaka, Murti

    2013-01-01

    Over the past few decades, single molecule investigations employing optical tweezers, AFM and TIRF microscopy have revealed that molecular behaviors are typically characterized by discrete steps or events that follow changes in protein conformation. These events, that manifest as steps or jumps, are short-lived transitions between otherwise more stable molecular states. A major limiting factor in determining the size and timing of the steps is the noise introduced by the measurement system. To address this impediment to the analysis of single molecule behaviors, step detection algorithms incorporate large records of data and provide objective analysis. However, existing algorithms are mostly based on heuristics that are not reliable and lack objectivity. Most of these step detection methods require the user to supply parameters that inform the search for steps. They work well, only when the signal to noise ratio (SNR) is high and stepping speed is low. In this report, we have developed a novel step detection method that performs an objective analysis on the data without input parameters, and based only on the noise statistics. The noise levels and characteristics can be estimated from the data providing reliable results for much smaller SNR and higher stepping speeds. An iterative learning process drives the optimization of step-size distributions for data that has unimodal step-size distribution, and produces extremely low false positive outcomes and high accuracy in finding true steps. Our novel methodology, also uniquely incorporates compensation for the smoothing affects of probe dynamics. A mechanical measurement probe typically takes a finite time to respond to step changes, and when steps occur faster than the probe response time, the sharp step transitions are smoothed out and can obscure the step events. To address probe dynamics we accept a model for the dynamic behavior of the probe and invert it to reveal the steps. No other existing method addresses

  9. Developing Sustainable Trauma Care Education in Egypt: STEPS to Success

    PubMed Central

    El-Shinawi, Mohamed; McCunn, Maureen; Sisley, Amy C.; El-Setouhy, Maged; Hirshon, Jon Mark

    2015-01-01

    Introduction As one of the leading causes of death and disability in the world, human trauma and injury disproportionately affects individuals in developing countries. To meet the need for improved trauma care in Egypt, the Sequential Trauma Emergency/Education ProgramS (STEPS) course was created through the collaborative effort of U.S. and Egyptian physicians. The objective of course development was to create a high quality, modular, adaptable and sustainable trauma care course that could be readily adopted by a lower- or middle- income country. Methods We describe the development, transition and host-nation sustainability of a trauma care training course between a high income Western nation and a lower-middle income Middle Eastern/Northern African country, including number of physicians trained and challenges to program development and sustainability. Results STEPS was developed at the University of Maryland, based in part on World Health Organization’s Emergency and Trauma Care materials, and introduced to the Egyptian Ministry of Health and Population (MOHP) and Ain Shams University in May 2006. To date, 639 physicians from multiple specialties have taken the 4-day course through the MOHP or public/governmental universities. In 2008, the course transitioned completely to the leadership of Egyptian academic physicians. Multiple Egyptian medical schools and the Egyptian Emergency Medicine Board now require STEPS or its equivalent for physicians in training. Conclusions Success of this collaborative educational program is demonstrated by the numbers of physicians trained, the adoption of STEPS by the Egyptian Emergency Medicine Board, and program continuance after transitioning to in-country leadership and trainers. PMID:25600355

  10. Multiple Sclerosis.

    PubMed

    Schiess, Nicoline; Calabresi, Peter A

    2016-08-01

    It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in cognitive, emotional, motoric, sensory, or visual domains. Patients are often struck in the prime of their lives as they attempt to move forward with career, and family. Since the previous 2010 Seminars in Neurology Pearls and Pitfalls issue, the world of MS has drastically changed and advanced. Here the authors address the ever-changing MS world in both treatment options and diagnostics, covering easily missed differential diagnoses, newly available immunomodulatory therapy, and the challenges of safely treating patients. PMID:27643903

  11. Terrace-Width Distributions (TWDs) of Touching Steps: Modification of the Fermion Analogy, with Implications for Measuring Step-Step Interactions on Vicinals

    NASA Astrophysics Data System (ADS)

    Einstein, T. L.; Sathiyanarayanan, Rajesh; Hamouda, Ajmi Bh.; Kim, Kwangmoo

    2010-03-01

    Using Monte Carlo simulations, we computefootnotetextRS, ABH, and TLE, Phys. Rev. B 80 (2009) 153415. the TWDs of surfaces in which steps can touch each other, forming multiple-atomic height steps, but cannot cross (no overhangs), and so inconsistent with the standard mapping to spinless fermions. Our numerical results show that the generalized Wigner distribution, with minor modifications at small step separations, gives a very good fit for TWDs of touching steps. (We also generate analytic results by generalizing results for extended fermions.footnotetextSiew-Ann Cheong and C.L. Henley, arXiv:0907.4228v1.) The interaction strength derived from the fit parameter indicates an effective attraction between steps, weakening the overall repulsion. The strength of this effective attraction decreases for larger mean-step separations and decreasing step-touching energies; describable via finite-size scaling. Hence, accurate extraction of the true repulsion strength requires multiple vicinalities.

  12. 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 ...

  13. 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,…

  14. 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.

  15. 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.

  16. The digital step edge

    NASA Technical Reports Server (NTRS)

    Haralick, R. M.

    1982-01-01

    The facet model was used to accomplish step edge detection. The essence of the facet model is that any analysis made on the basis of the pixel values in some neighborhood has its final authoritative interpretation relative to the underlying grey tone intensity surface of which the neighborhood pixel values are observed noisy samples. Pixels which are part of regions have simple grey tone intensity surfaces over their areas. Pixels which have an edge in them have complex grey tone intensity surfaces over their areas. Specially, an edge moves through a pixel only if there is some point in the pixel's area having a zero crossing of the second directional derivative taken in the direction of a non-zero gradient at the pixel's center. To determine whether or not a pixel should be marked as a step edge pixel, its underlying grey tone intensity surface was estimated on the basis of the pixels in its neighborhood.

  17. 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…

  18. Comparison one-step procedure with two-step procedure in percutaneous nephrolithotomy.

    PubMed

    Chen, Szu-Han; Wu, Wen-Jeng; Chou, Yii-Her; Yeh, Hsin-Chih; Tsai, Chia-Chun; Chueh, Kuang-Shun; Hou, Nien-Ting; Chiu, Siou-Jin; Tu, Hung-Pin; Li, Ching-Chia

    2014-04-01

    The aim of this study was to compare the effects of one-step percutaneous nephrolithotomy (PCNL) by the urologist alone and two-step PCNL by cooperating with the radiologist. We included 168 patients who underwent surgery by the same surgeon, 83 who underwent two-step PCNL, in which percutaneous nephrostomy insertion was performed by the radiologists on the day before endo-surgery, and 85 who underwent one-step PCNL, which involved the creation of a nephrostomy tract and performing the PCNL at the same time in the operating room, by a urologist. We compared the perioperative and postoperative parameters between these two groups. The result revealed that there were no significant differences between one-step and two-step PCNL in the decreases in haemoglobin level and blood transfusion volume, and the hospital stay was shorter in the one-step PCNL group. In addition, the one-step PCNL group was associated with significantly lower visual analogue score (VAS), which were 2.3, 1.1, and 0.4 on the post-operative days 1, 2, and 3, respectively, compared with 3.2, 1.7, and 1.0 in the two-step PCNL group. The number of parenteral analgesic prescriptions was fewer in the one-step PCNL group (0.8 ± 1.1 amps/vials) than in the two-step PCNL group (4.1 ± 2.4 amps/vials). Furthermore, different stone locations barely affected VAS and analgesic administrations. The results indicate that the one-step PCNL by the urologist alone, compared to two-step PCNL with the radiologist, has better wound pain outcome and shorter hospital stay with comparable successful rate and complication grade.

  19. 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.

  20. Steps to the moon

    USGS Publications Warehouse

    ,; Dale, Alvin E.

    1976-01-01

    On July 20, 1969, man walked on the surface of the Moon and began a new chapter of his studies that will eventually disclose the geologic nature of the Earth's nearest neighbor. Although he has finally reached the Moon and sampled its substance, much work and study remain before he will know the full scientific significance of the first landing. This booklet briefly summarizes the steps man has taken to understand the Moon and what he thinks he has learned to date as a result of his centuries-long speculations and studies.

  1. Experimentation: the next step

    PubMed Central

    Marinker, Marshall

    1987-01-01

    General practice has entered a period of accelerating change, and those responsible for planning its development now put forward a variety of promising proposals. Unless provision is made for large scale experimentation and scientific evaluation, the direction of future change will be determined not by evidence but by rhetoric. A framework for creating and evaluating a substantial programme of experimentation is suggested. The programme is the logical next step in the process of change which was given impetus by the publication of the government green paper. It should be seen as a professional, moral and political priority. PMID:3681850

  2. 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

  3. 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.

  4. 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…

  5. 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.

  6. 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…

  7. Early invitation to food and/or multiple micronutrient supplementation in pregnancy does not affect body composition in offspring at 54 months: follow-up of the MINIMat randomised trial, Bangladesh.

    PubMed

    Khan, Ashraful Islam; Kabir, Iqbal; Hawkesworth, Sophie; Ekström, Eva-Charlotte; Arifeen, Shams; Frongillo, Edward A; Persson, Lars Åke

    2015-07-01

    Growth patterns in early life are associated with later health. The effect of nutrition during in utero development on later body composition is unclear. We evaluated whether prenatal early invitation to food and/or multiple micronutrient supplementation (MMS) in pregnancy has an effect on offspring body composition at 54 months of age. In Maternal and Infant Nutrition Interventions in Matlab trial (ISRCTN16581394) in Bangladesh, 4436 pregnant women were randomised into six equally sized groups: double-masked supplementation with capsules of either 30 mg Fe and 400 μg folic acid, or 60 mg Fe and 400 μg folic acid, or MMS (15 micronutrients), was combined with a randomised early invitation (around 9 weeks) or a usual invitation (around 20 weeks) to start food supplementation (608 kcal 6 days per week). At 54 months, the body composition of the offspring was assessed by leg-to-leg bioelectrical impedance analysis. Of the 3267 live singletons with birth anthropometry, 2290 children were measured at 54 months, representing 70% of the live births. There was no interaction between the food and micronutrient supplementation on body composition outcomes. There were no significant differences in a range of anthropometric and body composition measurements, including weight, height, mid-upper arm circumference, head circumference, skinfold thickness, and fat mass and fat-free mass between the different prenatal food and micronutrient groups using an intention-to-treat analysis. This analysis shows that early invitation to food supplementation and MMS provided to rural Bangladeshi women during pregnancy did not affect offspring body composition at 54 months of age.

  8. 1992 STEP Symposium

    NASA Astrophysics Data System (ADS)

    Lui, Tony

    The year 1992 marks the quincentenary jubilee of the famous voyage of Christopher Columbus to the New World, a trip which initiated sustained contact between Europe and the American continent. Courageous explorations often lead to advancement of mankind, be they in uncharted territory or science. As much as Columbus was unaware of what lay in store for his voyage, we were just as poorly informed about what lay beyond our home planet when we began space exploration about three decades ago. There is much similarity among the pioneering spirits characteristic of both endeavors. It is thus fitting to celebrate this quincentenary occasion by declaring 1992 International Space Year (ISY).In conjunction with the COSPAR Meeting and the International Convention of the World Space Congress to be held in Washington, D.C., from August to September 1992, a 4-day symposium on the initial results from the Solar-Terrestrial Energy Program (STEP) Facilities and Theory Campaigns will be held at Johns Hopkins University, Applied Physics Laboratory, Laurel, Md., August 24-27. 1992.

  9. STEPS: JPL's Astrometric Exoplanet Survey

    NASA Technical Reports Server (NTRS)

    Shaklan, Stuart; Pravdo, Steve

    2008-01-01

    Presentation topics include: STEPS ground-based astrometry at Hale Telescope; the instrument; why astronomy and why M-dwarfs; motion of center of light about center of mass in photocentric orbit; photocentric motion vs. fractional mass; high-resolution imaging of STEPS targets; GU 802 p one possible orbit plotted with data, Keplerian frame; GJ 802 results; STEPS future; and a bibliography of STEPS papers.

  10. 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.

  11. 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 ...

  12. 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 ...

  13. 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,…

  14. 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…

  15. 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, ...

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. 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…

  1. 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…

  2. 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…

  3. Enhancing multiple disciplinary teamwork.

    PubMed

    Weaver, Terri E

    2008-01-01

    Multiple disciplinary research provides an opportunity to bring together investigators across disciplines to provide new views and develop innovative approaches to important questions. Through this shared experience, novel paradigms are formed, original frameworks are developed, and new language is generated. Integral to the successful construction of effective cross-disciplinary teams is the recognition of antecedent factors that affect the development of the team such as intrapersonal, social, physical environmental, organizational, and institutional influences. Team functioning is enhanced with well-developed behavioral, affective, interpersonal, and intellectual processes. Outcomes of effective multiple disciplinary research teams include novel ideas, integrative models, new training programs, institutional change, and innovative policies that can also influence the degree to which antecedents and processes contribute to team performance. Ongoing evaluation of team functioning and achievement of designated outcomes ensures the continued development of the multiple disciplinary team and confirmation of this approach as important to the advancement of science.

  4. 48 CFR 52.214-24 - Multiple Technical Proposals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Multiple Technical....214-24 Multiple Technical Proposals. As prescribed in 14.201-6(s), insert the following provision: Multiple Technical Proposals (APR 1984) In the first step of this two-step acquisition, solicited...

  5. Representing Multiplication

    ERIC Educational Resources Information Center

    Harries, Tony; Barmby, Patrick

    2008-01-01

    In this study, the authors wish to explore the use of visual representations in facilitating the understanding of multiplication. In doing so, they examine the different aspects of multiplication that they can access through different representations. In addition, they draw on a study that they have been carrying out looking at pupils' actual use…

  6. 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 ...

  7. Development of a "Steps Questionnaire".

    PubMed

    Gilbert, F S

    1991-07-01

    Thousands of men and women have begun their recovery from alcoholism through the support of Alcoholics Anonymous (AA) and its well-known "12-Step" program. The purpose of the present study was to develop a scale to measure alcoholics' levels of agreement with the first three of AA's 12 Steps and to test the relationship between sobriety and belief in these three steps. Using both factor analysis and Rasch analysis, two versions of a "Steps Questionnaire" were developed. A 96-member subset of the original subject pool was assessed quarterly for 1 year following inpatient treatment to determine the predictive validity of the questionnaire. The results of this study suggested that agreement with AA's first three steps can be measured and that agreement with AA's first step correlates with number of sober days posttreatment. The dichotomization of Steps Questionnaire scores into total agreement versus partial agreement with Step 1, and from this the reduction of uncertainty in the prediction of abstention over a lengthy follow-up period, provides support for AA's contention that total surrender to one's powerlessness over alcohol is part of the process of achieving abstention.

  8. 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…

  9. Multiple homicides.

    PubMed

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. Manipulation of step height and its effect on lactate metabolism during a one-minute anaerobic step test.

    PubMed

    Nguyen, Brian D; Gillum, Trevor L

    2015-06-01

    The purpose of this study was to observe the effects of the 1-minute anaerobic step test on lactate production. In addition, a comparison of postexercise lactate levels between the traditional 40-cm step height and a modified 20-cm step height was tested along with multiple biomechanical components such as torque, knee angle, and power. A convenience sample of 9 healthy moderately trained individuals were recruited for this experiment. Each subject performed the 1-minute anaerobic step test in a counterbalanced, crossover, and repeated-measures design. They performed 2 trials, 1 with a 40-cm step height and another with a 20-cm step height. Results showed statistical significance in terms of the postexercise lactate concentration (40 cm: 8.04 ± 2.13 mmol·L(-1); 20 cm: 6.18 ± 2.62 mmol·L(-1)) and lactate production (40 cm: 5.36 ± 2.73 mmol·L(-1); 20 cm: 3.06 ± 2.96 mmol·L(-1)) between the 2 step heights (p ≤ 0.05). With a lowered step height, the moment arm decreased significantly, which lowered the torque placed on the knee joint. Knee angle and power both decreased with a lowered step height of 20 cm. These results suggest that the 1-minute anaerobic step test is effective at eliciting lactate and can be used as an anaerobic exercise modality to train the anaerobic energy system. Furthermore, a step height of 40 cm seemed to be more effective at taxing the anaerobic energy system and eliciting lactate compared with a step height of 20 cm.

  15. Transoral Robotic Surgery: Step-by-Step Radical Tonsillectomy

    PubMed Central

    Millas, Teresa

    2014-01-01

    Introduction. Transoral robotic surgery (TORS) radical tonsillectomy is an emerging minimally invasive surgical procedure for the treatment of cancer of the tonsil. The detailed surgical technique and claims for its reproducibility have been previously published. Case Presentation. We present a patient with a T2N2bM0 epidermoid carcinoma of the tonsil to illustrate step by step the surgical procedure for TORS radical tonsillectomy. Neck dissection and TORS were staged. No surgical reconstruction of the defect was required. No tracheostomy was necessary. The patient could eat without any feeding tube and was on full oral diet on the fifth postoperative day. Discussion. The transoral approach offers the benefits of minimally invasive surgery to patients with cancer of the tonsil. The excellent exposure and high precision provided by robotic instrumentation allow the surgeon to closely follow and accomplish the surgical steps, which is the best warranty for safety and effectiveness. PMID:24808963

  16. 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.

  17. 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…

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. [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

  5. 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.

  6. 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.

  7. 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

  8. 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 ...

  9. 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 ...

  10. 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

  11. 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…

  12. 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…

  13. 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.

  14. 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.

  15. 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…

  16. 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…

  17. 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.

  18. Shapiro step at nonequilibrium conditions

    NASA Astrophysics Data System (ADS)

    Shukrinov, Yu. M.; Nashaat, M.; Kulikov, K. V.; Dawood, R.; El Samman, H.; El Sherbini, Th. M.

    2016-07-01

    Detailed numerical simulations of intrinsic Josephson junctions of high-temperature superconductors under external electromagnetic radiation are performed taking into account a charge imbalance effect. We demonstrate that the charge imbalance is responsible for a slope in the Shapiro step in the IV-characteristic. The value of slope increases with a nonequilibrium parameter. Coupling between junctions leads to the distribution of the slope's values along the stack. The nonperiodic boundary conditions shift the Shapiro step from the canonical position determined by Vss=\\hbar f /(2e) , where f is a frequency of external radiation. This fact makes the interpretation of the experimentally found Shapiro step shift by the charge imbalance effect ambiguous.

  19. 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...

  20. Stockpile Transition Enabling Program (STEP): Process and project requirements

    SciTech Connect

    Ma, Kwok Kee

    1993-06-01

    The Stockpile Transition Enabling Program (STEP) is aimed at identifying weapon components suitable for use in more than one weapon and for qualifying components so identified for multiple use. Work includes identifying the means to maintain the manufacturing capability for these items. This document provides the participants in STEP a common, consistent understanding of the process and requirements. The STEP objectives are presented and the activities are outlined. The STEP project selections are based on the customer needs, product applicability, and maturity of the technology used. A formal project selection process is described and the selection criteria are defined. The concept of {open_quotes}production readiness{close_quotes} is introduced, along with a summary of the project requirements and deliverables to demonstrate production readiness.

  1. Myeloma (multiple)

    PubMed Central

    2006-01-01

    Introduction Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose

  2. Muscle synergies involved in shifting the center of pressure while making a first step.

    PubMed

    Wang, Yun; Zatsiorsky, Vladimir M; Latash, Mark L

    2005-11-01

    We used the framework of the uncontrolled manifold (UCM) hypothesis to analyze multi-muscle synergies involved in making a step by a standing person. We hypothesized that leg and trunk muscles are organized into stable groups (muscle modes, M-modes) related to shifts of the center of pressure (COP) in the anterior-posterior and medio-lateral directions. Another hypothesis was that the magnitudes of the modes co-vary across repetitive trials to stabilize a certain magnitude of the COP shift in both directions. M-modes were defined using principal component analysis applied to indices of changes in the electromyographic (EMG) activity prior to releasing variable loads that were held by the subject using a pulley system. For the task of releasing the load behind the body three M-modes associated with a backward COP shift were defined. Four M-modes were defined for the task of releasing the load at the body side associated with a lateral COP shift. Multiple regression analysis was used to relate changes in the M-mode magnitudes to COP shifts. EMG changes prior to making a step were quantified over five 100 ms time windows before the lift-off of the stepping leg. Two components of the variance in the M-mode space computed across repetitions of a stepping task were quantified-a component that did not affect the average COP shift in a particular direction (variance within the UCM, V (UCM)), and a component that affected the COP shift (variance orthogonal to the UCM, V (ORT)). V (UCM) was significantly higher than V (ORT) for both directions of the COP shifts. This relation was observed for the M-modes in the stepping leg as well as in the support leg. The stepping leg showed a different time evolution of the ratio V (UCM)/V (ORT) such that the difference between the two variance components disappeared closer to the time of the lift-off. The findings corroborate both main hypotheses. The study supports a view that control of whole-body actions involves grouping the muscles

  3. 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

  4. 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…

  5. 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…

  6. Ten Steps to "TQM Plus."

    ERIC Educational Resources Information Center

    Kaufman, Roger; Hirumi, Atsusi

    1992-01-01

    Total Quality Management Plus (TQM) goes beyond customer satisfaction to consider quality of life, environmental conditions, crime rates, and health and well-being. Steps to integrate such concerns into the TQM process include being ready for challenges, creating a quality system to collect performance data, defining the ideal school and world…

  7. Pride Is the First Step

    ERIC Educational Resources Information Center

    Rourke, James; Boone, Elizabeth

    2008-01-01

    When visitors step inside Pocomoke (MD) Middle School, they are immediately surrounded by a profound sense of pride and high expectations. Students are actively engaged in instruction, the classroom walls are covered with student work, and the halls are lined with pictures of students demonstrating success. Beanbag chairs await eager readers,…

  8. 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.

  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. 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.

  11. 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.

  12. 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…

  13. 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

  14. Multiple Sclerosis

    PubMed Central

    2013-01-01

    Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. Much of what is known about MS has been learned from an animal model of the disease, experimental allergic encephalomyelitis. PMID:24381825

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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…

  20. [Multiple myeloma].

    PubMed

    Abe, Masahiro; Miki, Hirokazu; Nakamura, Shingen

    2016-03-01

    Owing to the positive clinical benefits obtained with new agents, complete remission (CR) can be used as a surrogate for overall survival, and should be achieved. Although multiple myeloma is a heterogeneous disease in terms of myeloma cell- and patient-related risk factors, patients should receive the most effective combination therapy based on proteasome inhibitors and/or immunomodulatory drugs (IMiDs) as backbone medication irrespective of the risks encountered in the setting of induction therapy ("one-size-fits-all" therapy), followed by consolidation/maintenance therapy to achieve CR with the ultimate goal of extended survival. Myeloma-defining biomarkers have been established to identify high-risk smoldering myeloma requiring treatment. The development of salvage treatments yielding better outcomes for relapsed/refractory myeloma is urgently needed. Upcoming novel molecular targeting agents with different modes of action and immunotherapeutic agents will be integrated into myeloma treatment regimens with a great therapeutic impact, and further evolution of the treatment paradigm for multiple myeloma is eagerly anticipated. PMID:27076236

  1. 4 Steps to Standards Integration

    ERIC Educational Resources Information Center

    Domine, Vanessa

    2006-01-01

    It is too easy for teachers and library media specialists to entangle themselves in the multiple strands of standards: State core curriculum content standards, National Educational Technology Standards for Students (NETS.S), National Educational Technology Standards for Teachers (NETS.T), and the Information Literacy Standards (ALA). To prevent…

  2. Increasing Running Step Rate Reduces Patellofemoral Joint Forces

    PubMed Central

    Lenhart, Rachel L.; Thelen, Darryl G.; Wille, Christa M.; Chumanov, Elizabeth S.; Heiderscheit, Bryan C.

    2013-01-01

    Purpose Increasing step rate has been shown to elicit changes in joint kinematics and kinetics during running, and has been suggested as a possible rehabilitation strategy for runners with patellofemoral pain. The purpose of this study was to determine how altering step rate affects internal muscle forces and patellofemoral joint loads, and then to determine what kinematic and kinetic factors best predict changes in joint loading. Methods We recorded whole body kinematics of 30 healthy adults running on an instrumented treadmill at three step rate conditions (90%, 100%, and 110% of preferred step rate). We then used a 3D lower extremity musculoskeletal model to estimate muscle, patellar tendon, and patellofemoral joint forces throughout the running gait cycles. Additionally, linear regression analysis allowed us to ascertain the relative influence of limb posture and external loads on patellofemoral joint force. Results Increasing step rate to 110% of preferred reduced peak patellofemoral joint force by 14%. Peak muscle forces were also altered as a result of the increased step rate with hip, knee and ankle extensor forces, and hip abductor forces all reduced in mid-stance. Compared to the 90% step rate condition, there was a concomitant increase in peak rectus femoris and hamstring loads during early and late swing, respectively, at higher step rates. Peak stance phase knee flexion decreased with increasing step rate, and was found to be the most important predictor of the reduction in patellofemoral joint loading. Conclusion Increasing step rate is an effective strategy to reduce patellofemoral joint forces and could be effective in modulating biomechanical factors that can contribute to patellofemoral pain. PMID:23917470

  3. Acta Clinica Croatica: progress of a journal step by step.

    PubMed

    Ramljak, Gordana

    2014-03-01

    The journal Acta Clinica Croatica (ACC) was founded in 1962 under the title Anali Bolnice Dr. M. Stojanović. In 1995, the title of the journal was changed into its present form and ever since all papers have been published in English. In 2000, the electronic (online) edition of the ACC was released in addition to the print version. The paper presents development of the journal from 1962 to 2012 based on the analysis of the following SCOPUS citation index parameters: type and number of documents published in the journal; number of citations; and number of domestic and foreign authors. The studied period was analyzed in three time segments: the period from 1995 to 1999, the period from 2000 to 2006 and the period from 2007 to 2012. The same parameters were analyzed in the Web of Science/SCI-Expanded bibliographic and citation index for the 2007-2012 period. The increasing number of documents, authors (both domestic and foreign) and citations demonstrates gradual rise in the quality, visibility and impact of the journal. The fifty years of experience show that a goal, at first very distant and almost unachievable, may be reached by progressing step by step.

  4. 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

  5. Readying Parents and Teachers for the Inclusion of Children with Disabilities: A Step-by-Step Process.

    ERIC Educational Resources Information Center

    Olson, Jennifer; Murphy, Cari Lee; Olson, Philip D.

    1999-01-01

    Provides insight into system-level changes needed to support inclusive preschool activities. Recognizes successful outcomes of inclusive programs as highly dependent on attitudes of parents and teachers. Describes a six-step process in developing successful inclusive programs in a rural Iowa community. Stresses the need for everyone affected to…

  6. [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

  7. 48 CFR 52.214-25 - Step Two of Two-Step Sealed Bidding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 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...

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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

  13. What Promotes Wisdom in 12-Step Recovery?

    PubMed

    DiGangi, Julia A; Majer, John M; Mendoza, Leslie; Droege, Jocelyn R; Jason, Leonard A; Contreras, Richard

    2014-01-01

    Research investigations on twelve-step groups such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) have addressed a number of resources associated with 12-step recovery. However, little is known about the role of wisdom, and whether aspects of 12-step participation might increase this resource among 12-step members. An exploratory analysis revealed that participants who reported having a "spiritual awakening" and considered themselves "members" of 12-step groups reported significantly higher levels of wisdom. Twelve-step meeting attendance was not significantly related to wisdom scores. Findings suggest certain aspects of 12-step involvement are associated with wisdom and may play a role in substance abuse recovery.

  14. 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

  15. 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)…

  16. Multiple sclerosis

    PubMed Central

    Boster, Aaron L.; Racke, Michael K.

    2013-01-01

    Summary Preliminary studies have suggested that a high salt diet may play a role in the development of autoimmune disease and possibly multiple sclerosis (MS). Promising clinical trial results for 2 new therapies for MS have been reported. Dimethyl fumarate, also known by its investigational name BG-12, became the third oral disease-modifying therapy for MS to be Food and Drug Administration (FDA)–approved in March 2013. Interestingly, dimethyl fumarate served as the active compound used for the treatment of psoriasis for decades. Alemtuzumab remains under investigation and is not currently FDA-approved for treatment of MS. Other drugs currently approved for alternative indications are being investigated for use in MS. Additionally, an investigation of alternative dosing strategies for glatiramer acetate suggests that patients may benefit from a higher dose formulation and less frequent medication administration. Advances in basic science research have identified another potential autoantigenic target in MS, KIR4.1, which may provide further insight into MS pathophysiology. PMID:24175156

  17. 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

  18. Multiple epiphyseal dysplasia

    PubMed Central

    2009-01-01

    Background Multiple epiphyseal dysplasia (MED) is a common genetically and clinically heterogeneous skeletal dysplasia characterized by early-onset osteoarthritis, mainly in the hip and knee, and mild-to-moderate short stature. Here we report on a 6-generation MED family with 17 affected members. Method The clinical and radiographic data on the 12 affected members still living were scrutinized. A structured inquiry comprising state of health and MED-related symptoms since birth up to the present time and the osteoarthritis outcome (KOOS) questionnaire were sent to all living family members with MED. The 5 known gene loci for autosomal dominant MED were analyzed for linkage, using fluorescence-labeled microsatellite markers. Linkage was ascertained with markers close to the COL9A2 gene, which was analyzed for mutations by sequencing. Results We identified an exon 3 donor splice mutation in the COL9A2 gene in all affected family members. Clinical, radiographic, and questionnaire data from affected family members suggested that MED caused by COL9A2 mutations starts in early childhood with knee pain accompanied by delayed ossification of femoral epiphyses. The disease then either stabilizes during puberty or progresses with additional joints becoming affected; joint surgery might be necessary. The progression of the disease also affects muscles, with increasing atrophy, resulting in muscle fatigue and pain. Muscular atrophy has not been reported earlier in cases with COL9A2 mutations. Interpretation In a patient with clinically suspected or verified MED, it is important to perform DNA-based analysis to identify a possible disease-causing mutation. This information can be used to carry out genetic risk assessment of other family members and to achieve an early and correct diagnosis in the children. PMID:19995321

  19. 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.

  20. Staircase Structure of Shapiro Steps

    NASA Astrophysics Data System (ADS)

    Shukrinov, Yu. M.; Rahmonov, I. R.; Nashaat, M.

    2015-12-01

    We investigate IV-characteristics of coupled Josephson junctions which model the intrinsic Josephson junctions in high temperature superconductors under external electromagnetic radiation. A staircase structure of Shapiro steps is found in the branching region. Its origin is related to the coupling between junctions and their switching from rotating to oscillating states. This conclusion is tested by detailed analysis of the IV-characteristics as for total stack and for each junction in the stack. IV-curves of junctions in the stack are compared with the average of time derivative of phase difference. Experimental observation of this staircase structure would give us a proof of coupling between junctions and a way for precise measurement of its value. Such investigations would be also useful for a diagnostic of Josephson junctions in the stack.

  1. 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…

  2. A Step by Step Protocol for Subretinal Surgery in Rabbits.

    PubMed

    Al-Nawaiseh, Sami; Thieltges, Fabian; Liu, Zengping; Strack, Claudine; Brinken, Ralf; Braun, Norbert; Wolschendorf, Marc; Maminishkis, Arvydas; Eter, Nicole; Stanzel, Boris V

    2016-09-13

    Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in adults in industrially developed countries. RPE transplantation appears to be a promising therapy, as it may replace dysfunctional RPE, restore its function, and thereby vision. Here we describe a method for transplanting a cultured RPE monolayer on a scaffold into the subretinal space (SRS) of rabbits. After vitrectomy xenotransplants were delivered into the SRS using a custom made shooter consisting of a 20-gauge metallic nozzle with a polytetrafluoroethylene (PTFE) coated plunger. The current technique evolved in over 150 rabbit surgeries over 6 years. Post-operative follow-up can be obtained using non-invasive and repetitive in vivo imaging such as spectral domain optical coherence tomography (SD-OCT) followed by perfusion-fixed histology. The method has well-defined steps for easy learning and high success rate. Rabbits are considered a large eye animal model useful in preclinical studies for clinical translation. In this context rabbits are a cost-efficient and perhaps convenient alternative to other large eye animal models.

  3. A Step by Step Protocol for Subretinal Surgery in Rabbits.

    PubMed

    Al-Nawaiseh, Sami; Thieltges, Fabian; Liu, Zengping; Strack, Claudine; Brinken, Ralf; Braun, Norbert; Wolschendorf, Marc; Maminishkis, Arvydas; Eter, Nicole; Stanzel, Boris V

    2016-01-01

    Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in adults in industrially developed countries. RPE transplantation appears to be a promising therapy, as it may replace dysfunctional RPE, restore its function, and thereby vision. Here we describe a method for transplanting a cultured RPE monolayer on a scaffold into the subretinal space (SRS) of rabbits. After vitrectomy xenotransplants were delivered into the SRS using a custom made shooter consisting of a 20-gauge metallic nozzle with a polytetrafluoroethylene (PTFE) coated plunger. The current technique evolved in over 150 rabbit surgeries over 6 years. Post-operative follow-up can be obtained using non-invasive and repetitive in vivo imaging such as spectral domain optical coherence tomography (SD-OCT) followed by perfusion-fixed histology. The method has well-defined steps for easy learning and high success rate. Rabbits are considered a large eye animal model useful in preclinical studies for clinical translation. In this context rabbits are a cost-efficient and perhaps convenient alternative to other large eye animal models. PMID:27684952

  4. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-04-12

    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.

  5. 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

  6. A Novel Multi-carrier Radar for High-speed Wide-bandwidth Stepped-Frequency GPR

    NASA Astrophysics Data System (ADS)

    Kyoo Kim, Dong; Choi, Young Woo; Kang, Do Wook

    2015-04-01

    the paved road. To make it fast, the frequency step or the dwell time can be varied. But, increasing the frequency step affects the scanning time range performance, and decreasing the dwell time reduces SNR. In this paper, we introduce a novel multi-carrier radar technique, the step frequency multi-carrier (SFMC) which sends multiple CW signals simultaneously to speed up the scanning operation, where no reduction of the frequency step and the dwell time is required. In this paper, we apply the orthogonal frequency division multiplexing technique to the simultaneous sending of multiple CW signals. The suggested technique is in the category of the stepped-frequency GPR in that they are based on the frequency domain measurement. They have theoretically almost the same accuracy and SNR. But the scanning time of the suggested technique is incomparably fast than stepped-frequency GPR; hundreds of CW signals can be radiated at one time. To get the nice property, we need to pay additional signal processing process for it. In this paper, we handle the signal processing about impairments such as DC frequency, phase discontinuity, channel estimation, and frequency-edge non-linearity problem. Some simulation and experimental results are shown to address the impairments and performance of the suggested technique.

  7. 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

  8. 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.

  9. The Affective Side: Parenting for Achievement.

    ERIC Educational Resources Information Center

    Strop, Jean

    2003-01-01

    This article describes key steps parents can take to develop an achievement orientation in gifted children: heal the gifted child within the parent; give consistent messages; develop early independence; utilize encouragement; develop multiple self-definitions; set challenging but realistic goals; and model persistence. (Author/CR)

  10. 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…

  11. Cyberbullying among adolescents: the role of affective and cognitive empathy, and gender.

    PubMed

    Ang, Rebecca P; Goh, Dion H

    2010-08-01

    The purpose of the study was to examine the association between affective empathy, cognitive empathy, and gender on cyberbullying among adolescents. Participants were 396 adolescents from Singapore with age ranging from 12 to 18 years. Adolescents responded to a survey with scales measuring both affective and cognitive empathy, and cyberbullying behavior. A three-step hierarchical multiple regression analysis was used with cyberbullying scores as the dependent variable. Gender was dummy coded and both affective and cognitive empathy were centered using the sample mean prior to creating interaction terms and entering them into the regression equations. The testing, probing and interpretation of interaction effects followed established statistical procedures. Results from hierarchical multiple regression analysis indicated a significant three-way interaction. At low affective empathy, both boys and girls who also had low cognitive empathy had higher scores on cyberbullying than those who had high cognitive empathy. This pattern of results was similarly found for boys at high affective empathy. However, for girls, high or low levels of cognitive empathy resulted in similar levels of cyberbullying. Implications of these findings include the need for empathy training and the importance of positive caregiver-child relationships in reducing cyberbullying behavior among adolescents.

  12. Postural instability in Parkinson Disease: to step or not to step.

    PubMed

    Kimmell, Kristopher; Pulusu, Vinay K; Bharucha, Kersi J; Ross, Elliott D

    2015-10-15

    Postural instability is a key feature of Parkinson Disease that is associated with falls and morbidity. We designed a pull apparatus to quantitatively measure the force needed to pull subjects off-balance. Thirteen Controls and eight individuals with Parkinson Disease (PD) were evaluated. All individuals with PD reported subjective symptoms of postural instability and were symptomatic for approximately 9.4years when tested. No significant differences were found between Controls and PD subjects in the magnitude of force required to pull them off-balance. None of the Controls fell and all took a step into the direction of pull to maintain their balance. 59% of the time PD subjects fell because they did not take a step in the direction of pull to maintain their center of mass (COM) over their feet, thus indicating a deficiency in postural reflexes. If they fell on the first pull, PD subjects did not show a learning effect when pulled multiple times in the same direction. The utility of the Pull Test to detect postural instability is related to the subject's behavioral response, not the force needed to pull them off balance. Our findings may also help explain certain features of the PD gait as an attempt by subjects to avoid postural instability by not placing their COM in gravitationally unstable positions.

  13. Step initiation in Parkinson's disease: influence of initial stance conditions.

    PubMed

    Rocchi, Laura; Chiari, Lorenzo; Mancini, Martina; Carlson-Kuhta, Patricia; Gross, Anne; Horak, Fay B

    2006-10-01

    In this study, we investigated how the size of preparatory postural adjustments prior to step initiation, and step length and velocity depend on initial stance width in patients with Parkinson's disease (PD) both in the ON and OFF levodopa states and in healthy elderly subjects. Twenty-one subjects with idiopathic PD and 24 age-matched healthy control subjects took two steps starting with feet on a two-plate force-platform, from either narrow or wide stance width. We measured how the magnitude of anticipatory postural adjustments (APA) and step characteristics scaled with stance width. Results showed that preparation for step initiation from wide stance was associated with a larger lateral and backward center of pressure (CoP) displacement than from narrow stance. Velocity and length of the first step were also sensitive to initial stance conditions, probably in relation with the differences in the corresponding APA. On the contrary, the duration of APA was not significantly affected by initial stance width, but it was longer in PD compared to healthy subjects, and speeded up by levodopa. Although subjects with PD did scale up the size of their APA with stance width, they had much more difficulty initiating a step from a wide stance than from a narrow stance, as shown by the greater differences from control subjects in the magnitude of the APA. Our results support the hypothesis that PD subjects maintain a narrow stance as a compensation for their inability to sufficiently increase the size of their lateral APA to allow fast step initiation in wide stance.

  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. Multiple sclerosis - resources

    MedlinePlus

    Resources - multiple sclerosis ... The following organizations provide information on multiple sclerosis : Multiple Sclerosis Foundation -- www.msfocus.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/multiple_sclerosis National ...

  16. Effect of multifocal lens glasses on the stepping patterns of novice wearers.

    PubMed

    Beschorner, Kurt E; Milanowski, Autumn; Tomashek, Dennis; Smith, Roger O

    2013-09-01

    Multifocal lens glasses (MfLs) negatively affect vision, increase falling risk and contribute to gait changes during stepping. Previous studies on the effects of MfLs on gait have focused on experienced wearers. Thus, the initial response of first-time wearers, who may face significant challenges in adapting to these glasses, is not well understood. This study aimed to quantify the effects of MfLs on novice wearers during stepping up and down. Additionally, young adults were compared against a middle-aged adults to determine the validity of convenience sampling in testing novice response to MfLs. Fifteen young adults (18-34 y.o.) and seven middle-aged adults (46-56 y.o.) were recruited to perform stepping trials while wearing progressive MfLs and blank single lens glasses. Participants stepped up and down from a 75 mm and 150 mm step in randomized order. Step placement, minimum toe clearance, lower body kinematics and stepping time were measured during step up. Step placement, minimum heel clearance, vertical forces and stepping time were measured during step down. MfLs significantly increased toe clearance in the lead and trailing legs, hip flexion, knee flexion and stepping time during step up and increased vertical forces and stepping time during step down. Step placement and hip angle explained 17% of the toe clearance variability. Changes during step up suggest a more conservative adaptation while increased forces during step down suggest a reduced level of control. No age group effects were observed, which supports the use of convenience sampling for evaluating the novice response to MfLs. PMID:23770232

  17. 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.

  18. MLREG, stepwise multiple linear regression program

    SciTech Connect

    Carder, J.H.

    1981-09-01

    This program is written in FORTRAN for an IBM computer and performs multiple linear regressions according to a stepwise procedure. The program transforms and combines old variables into new variables, prints input and transformed data, sums, raw sums or squares, residual sum of squares, means and standard deviations, correlation coefficients, regression results at each step, ANOVA at each step, and predicted response results at each step. This package contains an EXEC used to execute the program,sample input data and output listing, source listing, documentation, and card decks containing the EXEC sample input, and FORTRAN source.

  19. 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…

  20. 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,...

  1. 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...

  2. 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,...

  3. 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…

  4. 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.

  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. The 5-Step Method: Principles and Practice

    ERIC Educational Resources Information Center

    Copello, Alex; Templeton, Lorna; Orford, Jim; Velleman, Richard

    2010-01-01

    This article includes a description of the 5-Step Method. First, the origins and theoretical basis of the method are briefly described. This is followed by a discussion of the general principles that guide the delivery of the method. Each step is then described in more detail, including the content and focus of each of the five steps that include:…

  7. 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.

  8. 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 ...

  9. 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 ...

  10. A comparison of the effects of visual deprivation and regular body weight support treadmill training on improving over-ground walking of stroke patients: a multiple baseline single subject design.

    PubMed

    Kim, Jeong-Soo; Kang, Sun-Young; Jeon, Hye-Seon

    2015-01-01

    The body-weight-support treadmill (BWST) is commonly used for gait rehabilitation, but other forms of BWST are in development, such as visual-deprivation BWST (VDBWST). In this study, we compare the effect of VDBWST training and conventional BWST training on spatiotemporal gait parameters for three individuals who had hemiparetic strokes. We used a single-subject experimental design, alternating multiple baselines across the individuals. We recruited three individuals with hemiparesis from stroke; two on the left side and one on the right. For the main outcome measures we assessed spatiotemporal gait parameters using GAITRite, including: gait velocity; cadence; step time of the affected side (STA); step time of the non-affected side (STN); step length of the affected side (SLA); step length of the non-affected side (SLN); step-time asymmetry (ST-asymmetry); and step-length asymmetry (SL-asymmetry). Gait velocity, cadence, SLA, and SLN increased from baseline after both interventions, but STA, ST-asymmetry, and SL-asymmetry decreased from the baseline after the interventions. The VDBWST was significantly more effective than the BWST for increasing gait velocity and cadence and for decreasing ST-asymmetry. VDBWST is more effective than BWST for improving gait performance during the rehabilitation for ground walking.

  11. The discriminant capabilities of stability measures, trunk kinematics, and step kinematics in classifying successful and failed compensatory stepping responses by young adults.

    PubMed

    Crenshaw, Jeremy R; Rosenblatt, Noah J; Hurt, Christopher P; Grabiner, Mark D

    2012-01-01

    This study evaluated the discriminant capability of stability measures, trunk kinematics, and step kinematics to classify successful and failed compensatory stepping responses. In addition, the shared variance between stability measures, step kinematics, and trunk kinematics is reported. The stability measures included the anteroposterior distance (d) between the body center of mass and the stepping limb toe, the margin of stability (MOS), as well as time-to-boundary considering velocity (TTB(v)), velocity and acceleration (TTB(a)), and MOS (TTB(MOS)). Kinematic measures included trunk flexion angle and angular velocity, step length, and the time after disturbance onset of recovery step completion. Fourteen young adults stood on a treadmill that delivered surface accelerations necessitating multiple forward compensatory steps. Thirteen subjects fell from an initial disturbance, but recovered from a second, identical disturbance. Trunk flexion velocity at completion of the first recovery step and trunk flexion angle at completion of the second step had the greatest overall classification of all measures (92.3%). TTB(v) and TTB(a) at completion of both steps had the greatest classification accuracy of all stability measures (80.8%). The length of the first recovery step (r ≤ 0.70) and trunk flexion angle at completion of the second recovery step (r ≤ -0.54) had the largest correlations with stability measures. Although TTB(v) and TTB(a) demonstrated somewhat smaller discriminant capabilities than trunk kinematics, the small correlations between these stability measures and trunk kinematics (|r| ≤ 0.52) suggest that they reflect two important, yet different, aspects of a compensatory stepping response.

  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. Mechanical work performed by individual limbs of transfemoral amputees during step-to-step transitions: Effect of walking velocity.

    PubMed

    Bonnet, Xavier; Villa, Coralie; Fodé, Pascale; Lavaste, Francois; Pillet, Hélène

    2014-01-01

    The greater metabolic demand during the gait of people with a transfemoral amputation limits their autonomy and walking velocity. Major modifications of the kinematic and kinetic patterns of transfemoral amputee gait quantified using gait analysis may explain their greater energy cost. Donelan et al. proposed a method called the individual limb method to explore the relationships between the gait biomechanics and metabolic cost. In the present study, we applied this method to quantify mechanical work performed by the affected and intact limbs of transfemoral amputees. We compared a cohort of six active unilateral transfemoral amputees to a control group of six asymptomatic subjects. Compared to the control group, we found that there was significantly less mechanical work produced by the affected leg and significantly more work performed by the unaffected leg during the step-to-step transition. We also found that this mechanical work increased with walking velocity; the increase was less pronounced for the affected leg and substantial for the unaffected leg. Finally, we observed that the lesser work produced by the affected leg was linked to the increase in the hip flexion moment during the late stance phase, which is necessary for initiating knee flexion in the affected leg. It is possible to quantify the mechanical work performed during gait by people with a transfemoral amputation, using the individual limb method and conventional gait laboratory equipment. The method provides information that is useful for prosthetic fitting and rehabilitation.

  14. 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.

  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. 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.

  17. 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.

  18. Multiple Layers of Stress-Induced Regulation in tRNA Biology

    PubMed Central

    Huang, Hsiao-Yun; Hopper, Anita K.

    2016-01-01

    tRNAs are the fundamental components of the translation machinery as they deliver amino acids to the ribosomes during protein synthesis. Beyond their essential function in translation, tRNAs also function in regulating gene expression, modulating apoptosis and several other biological processes. There are multiple layers of regulatory mechanisms in each step of tRNA biogenesis. For example, tRNA 3′ trailer processing is altered upon nutrient stress; tRNA modification is reprogrammed under various stresses; nuclear accumulation of tRNAs occurs upon nutrient deprivation; tRNA halves accumulate upon oxidative stress. Here we address how environmental stresses can affect nearly every step of tRNA biology and we describe the possible regulatory mechanisms that influence the function or expression of tRNAs under stress conditions. PMID:27023616

  19. A Step-by-Step Teaching Technique for Teachers with Adult Students of Mathematics

    ERIC Educational Resources Information Center

    McDonald, Betty

    2013-01-01

    Step-by-step teaching is a researcher-designed innovative process that takes the adult learner, step-by-step, from his present level of understanding to the required level. The technique is based on well-researched and accepted pedagogical practices set in their psychological, sociological, and andragogical perspectives. Using a convenience sample…

  20. 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

  1. [Multiple agenesis and prosthetic restoration].

    PubMed

    Renault, P

    1990-03-01

    Cases of multiple agenesia present some difficulties in the treatment planing. Three situations may be encountered: limited agenesia, restored by a fixed, bonded or cemented prosthesis, multiple uni- or bimaxillary agenesia without remaining of deciduous teeth, restored by a fixed, bonded or cemented prosthesis or the partial adjacent prosthesis, multiple uni- or bimaxillary agenesia with remaining of deciduous teeth, restored by means of a supra-dental prosthesis. The first two situations have been described in dental literature and are relatively easy to treat. The same is not true for the third situation, where the decision to keep the temporary teeth considerably increases the difficulty of prosthetic restoration. This subject will be illustrated by the presentation of a clinical case of multiple bi-maxillary agenesia. The patient has: on the maxilla: an absence of 9 permanent teeth (18, 15, 14, 12, 22, 23, 24, 25, 28) and the presence of 4 deciduous teeth (62, 63, 64, 65), on the mandible: an absence of all permanent teeth, with the exception of 36 and 46, and the remaining of 4 deciduous teeth (75, 73, 83, 84). The remaining of deciduous teeth and the presence of a very high inter-arch space led to opting for dental coverage so as to keep the deciduous teeth and a proper vertical dimension. The patient wished to solve his "problem" in the maxilla first, and is not wanting to undergo the extraction of his deciduous teeth. The following therapeutic proposal was adapted: On the maxilla, a three-step procedure: first step: building of metal copings on 13, 16 and 26 and metal-ceramic crowns on 11 and 21, second step: building of telescop crowns on 16 and 26 and clasps on 13, 11 and 21, third step: casting of the removable partial denture framework and soldering to the telescop crowns and clasps. On the mandible, a provisional restoration using a supra-dental resin removable partial denture with ceramic occlusal surfaces was adopted. The aesthetic and functional

  2. 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

  3. 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.

  4. On the Performance of Multiple Pulse Multiple Delay UWB Modulation

    SciTech Connect

    Nekoogar, F; Dowla, F U

    2003-05-23

    Multiple access (MA) in UWB communication is an area of active research. In this paper we introduce and study the performance of a new MA scheme in the context of multiple transmitted-reference short duration (nsec) chirp pulses in the presence of additive white Gaussian noise (AWGN). The transmitted-reference (T-R) receiver is extended using multiple orthogonal pulses. The proposed UWB receiver samples the receiver autocorrelation function (ACF) at both zero- and non-zero lags, thus sampling and matching the shape of ACFs rather than just the shape of the received pulses. Sampling of non-zero ACF lags is a significant new approach. The scheme proposed in this paper is a step towards combining the multi-pulse approach and T-R modulation in a multiple access ultra wideband (MA-UWB) communications system. Improved bit error rate performance over a conventional zero-lag receiver (i.e. energy detection receiver) is demonstrated by simulation. Analytical expressions for the system BER are also derived and confirmed through simulations for the system.

  5. Multiple myeloma involving the orbit.

    PubMed

    Fay, A M; Leib, M L; Fountain, K S

    1998-01-01

    Multiple myeloma is a plasma cell malignancy often associated with destructive skeletal lesions. Orbital involvement in multiple myeloma is rare. Risk factors for orbital involvement have not been established, although risk may vary with immunoglobulin subtype. Early detection of orbital plasmacytoma may affect treatment and clinical course. A case is reported of multiple myeloma without elevated serum immunoglobulins that involves the orbit, and the implications of early detection are discussed. The patient was first examined by an ophthalmologist 13 months after multiple myeloma was diagnosed and 5 months after the external appearance of an orbital tumor. Urine protein electrophoresis demonstrated kappa light chains. Hypergammaglobulinemia was not detected. Plain-film roentgenography showed orbital involvement at the time of initial diagnosis. An impressive clinical response to external beam radiation therapy was seen. Attention to immunoprotein characteristics in multiple myeloma may help to identify risk factors for orbital involvement. Early detection may permit safer and equally effective treatment. All patients with multiple myeloma should undergo thorough ophthalmic examination at the time of initial diagnosis.

  6. A Versatile Step-Up/Step-Down Switched-Capacitor-Based DC-DC Converter

    NASA Astrophysics Data System (ADS)

    Wei, Chia-Ling; Wu, Lu-Yao; Yang, Hsiu-Hui; Tsai, Chien-Hung; Liu, Bin-Da; Chang, Soon-Jyh

    For battery-powered electronic products, one way to extend battery life is to use a versatile step-up/step-down DC-DC converter. A new versatile step-up/step-down switched-capacitor-based converter structure is proposed, and its efficiency is analyzed. In the step-down case, the efficiency is the same as, or even better than the efficiency of linear regulators.

  7. 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.

  8. 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.

  9. 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.

  10. [Familial multiple cavernomatosis].

    PubMed

    Terriza, F; Amrani, Y; Asencio, J J; Goberna, E; Casado, A; Peralta, J I

    1997-04-01

    We present a family study of multiple cavernomatosis which affected a boy of six, his mother and two brothers. It was seen clinically as epileptic crises, focal neurological defects and frequent headaches. In our case, the condition started as a syndrome of intracranial hypertension with progressive headache and vomiting. During the illness, localizing neurological signs due to bleeding were seen. Amongst these were acute left hemiparesia and paralysis of vertical gaze. Other members of the family remain symptom-free. In a search for angiomas at other sites none were found in the patient or his family. Recently the gene giving rise to the familial cerebral cavernosa malformation has been found to be a locus on chromosome 7. We discuss the findings on neuro-imaging, emphasizing the importance of magnetic resonance (MR) both in diagnosis and finding affected asymptomatic family members, because of its great sensitivity and specificity. Angiography is not a suitable technique for this since they behave as hidden malformations. We also point out its importance as a way of following-up the illness and for evaluation of possible complications due to progressive growth or sudden haemorrhage, which may indicate the need for treatment. Finally we emphasize the different characteristics of MR signals in this type of lesion since cavernomatasa malformations are dynamic lesions. PMID:9172920

  11. A vibrators alternation stepping ultrasonic motor.

    PubMed

    Jin, Jiamei; Zhao, Chunsheng

    2006-12-22

    A new concept of a vibrators alternation stepping ultrasonic motor, based on longitudinal vibrations of rectangular Langevin resonators, is presented. The new motor fed by a single-phase resource without feedback is capable of bi-directions step displacements without accumulative displacement error. The step angle is 1.44 degrees, when the 150 grooves on the rotor are used in positioning. The average rotation speed without load in one step is 16.49-14.65 rad/s, and the braking torque is 0.071-0.088 Nm in operating frequency 30 kHz and operation voltage 200 V.

  12. 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.

  13. 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.

  14. 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.

  15. Information theory and phenomenology of multiple hadronic production

    SciTech Connect

    Wilk, G. ); Wlodarczyk, Z. )

    1991-02-01

    Multiple hadronic production is usually visualized as a two-step process: the formation of some well-defined intermediate objects such as strings or fireballs and their subsequent hadronization (decays). It is shown how information theory provides us with a model-independent tool in dealing with the hadronization step for which the most plausible distributions of hadrons are formed.

  16. Schizophrenic reasoning about affect-laden material.

    PubMed

    Chapman, L J; Chapman, J P

    1975-10-01

    Drug-free schizophrenic patients (N equals 74) and nonpsychotic subjects (N equals 206) were given a test of affect-laden and affectively neutral multiple choice analogy items. The two subtests were matched on several psychometric characteristics that determine the power of the test to distinguish the more able from the less able normal subjects. Neither newly admitted schizophrenic nor long-term chronic schizophrenic patients performed differently on the affective subtest than on the neutral subtest. The many published findings of a cognitive deficit in schizophrenia in response to affect-laden stimuli can probably be attributed to the inappropriate use of unmatched tested. PMID:1180657

  17. Multiple-grid acceleration of Lax-Wendroff algorithms

    NASA Technical Reports Server (NTRS)

    Johnson, G. M.

    1982-01-01

    A technique for accelerating the convergence of a one-step Lax-Wendroff method to a steady-state solution is discussed and its applicability extended to the more general class of two-step Lax-Wendroff methods. Several two-step methods which lead to quite efficient multiple grid algorithms are discussed. Computational results are presented using the full two dimensional Euler equations for both subcritical and shocked supercritical flows. Extensions and generalizations are mentioned.

  18. 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…

  19. [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

  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.

  1. Stepping back from the property line: a perspective from regulatory theory.

    PubMed

    Dent, Chris

    2013-12-01

    There are multiple populations affected by issues associated with the excision and use of human tissue, each with different interests. There are also multiple subject matters for regulation; multiple regulatory goals that inform the system; and multiple strategies that may contribute to the attainment of those goals. This article outlines a range of regulatory mechanisms and suggests that a property regime is only one method of regulation in this area. Others may need to be considered to take account of the interests of all who may be affected, PMID:24597381

  2. Stepping back from the property line: a perspective from regulatory theory.

    PubMed

    Dent, Chris

    2013-12-01

    There are multiple populations affected by issues associated with the excision and use of human tissue, each with different interests. There are also multiple subject matters for regulation; multiple regulatory goals that inform the system; and multiple strategies that may contribute to the attainment of those goals. This article outlines a range of regulatory mechanisms and suggests that a property regime is only one method of regulation in this area. Others may need to be considered to take account of the interests of all who may be affected,

  3. 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.

  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. 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.

  6. 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.

  7. Executive function is necessary for the regulation of the stepping activity when stepping in place in older adults.

    PubMed

    Dalton, Christopher; Sciadas, Ria; Nantel, Julie

    2016-10-01

    To determine the effect of age on stepping performance and to compare the cognitive demand required to regulate repetitive stepping between older and younger adults while performing a stepping in place task (SIP). Fourteen younger (25.4 ± 6.5) and 15 older adults (71.0 ± 9.0) participated in this study. They performed a seated category fluency task and Stroop test, followed by a 60 s SIP task. Following this, both the cognitive and motor tasks were performed simultaneously. We assessed cognitive performance, SIP cycle duration, asymmetry, and arrhythmicity. Compared to younger adults, older adults had larger SIP arrhythmicity both as a single task and when combined with the Category (p < 0.001) and Stroop (p < 0.01) tasks. Older adults also had larger arrhythmicity when dual tasking compared to SIP alone (p < 0.001). Older adults showed greater SIP asymmetry when combined with Category (p = 0.006) and Stroop (p = 0.06) tasks. Finally, they had lower cognitive performance than younger adults in both single and dual tasks (p < 0.01). Age and type of cognitive task performed with the motor task affected different components of stepping. While SIP arrhythmicity was larger for all conditions in older compared to younger adults, cycle duration was not different, and asymmetry tended to be larger during SIP when paired with a verbal fluency task. SIP does not require a high level of control for dynamic stability, therefore demonstrating that higher-level executive function is necessary for the regulation of stepping activity independently of the regulation of postural balance. Furthermore, older adults may lack the cognitive resources needed to adequately regulate stepping activity while performing a cognitive task relying on the executive function.

  8. 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.

  9. Toilet Training: Children Step Up to Independence.

    ERIC Educational Resources Information Center

    Stephens, Karen

    1999-01-01

    Suggests that mastering the toilet is a significant step for young children, and one of childhood's earliest rites of passage. Suggests that in learning to control body functions, toddlers step toward independence, self-reliance and personal responsibility. Urges child care workers to work with parents to identify a child's readiness and to agree…

  10. 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 ...

  11. 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...

  12. 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...

  13. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  14. 15 CFR 732.1 - Steps overview.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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, 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...

  16. 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…

  17. Stepped-Pin Clevis Resists Jamming

    NASA Technical Reports Server (NTRS)

    Killgrove, T. O.

    1985-01-01

    Pin modification allows pyrotechnic release devices to operate more smoothly. New clevis pin has stepped diameters to prevent bending as it exits yoke. In contrast, conventional unstepped clevis pin bends and jams as it is withdrawn. Stepped pin design suitable for explosive and possible hammer driven pin sullers.

  18. 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

  19. 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...

  20. 15 CFR 732.3 - Steps regarding the ten general prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  1. 15 CFR 732.3 - Steps regarding the ten general prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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...

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. Step length estimation using handheld inertial sensors.

    PubMed

    Renaudin, Valérie; Susi, Melania; Lachapelle, Gérard

    2012-01-01

    In this paper a novel step length model using a handheld Micro Electrical Mechanical System (MEMS) is presented. It combines the user's step frequency and height with a set of three parameters for estimating step length. The model has been developed and trained using 12 different subjects: six men and six women. For reliable estimation of the step frequency with a handheld device, the frequency content of the handheld sensor's signal is extracted by applying the Short Time Fourier Transform (STFT) independently from the step detection process. The relationship between step and hand frequencies is analyzed for different hand's motions and sensor carrying modes. For this purpose, the frequency content of synchronized signals collected with two sensors placed in the hand and on the foot of a pedestrian has been extracted. Performance of the proposed step length model is assessed with several field tests involving 10 test subjects different from the above 12. The percentages of error over the travelled distance using universal parameters and a set of parameters calibrated for each subject are compared. The fitted solutions show an error between 2.5 and 5% of the travelled distance, which is comparable with that achieved by models proposed in the literature for body fixed sensors only.

  7. Single adatom dynamics at monatomic steps of free-standing few-layer reduced graphene

    PubMed Central

    Chang, Haixin; Saito, Mitsuhiro; Nagai, Takuro; Liang, Yunye; Kawazoe, Yoshiyuki; Wang, Zhongchang; Wu, Hongkai; Kimoto, Koji; Ikuhara, Yuichi

    2014-01-01

    Steps and their associated adatoms extensively exist and play prominent roles in affecting surface properties of materials. Such impacts should be especially pronounced in two-dimensional, atomically-thin membranes like graphene. However, how single adatom behaves at monatomic steps of few-layer graphene is still illusive. Here, we report dynamics of individual adatom at monatomic steps of free-standing few-layer reduced graphene under the electron beam radiations, and demonstrate the prevalent existence of monatomic steps even down to unexpectedly ultrasmall lateral size of a circular diameter of ~5 Å. Single adatom prefers to stay at the edges of the atomic steps of few-layer reduced graphene and evolve with the steps. Moreover, we also find that how the single adatom behaves at atomic step edges can be remarkably influenced by the type of adatoms and step edges. Such single adatoms at monatomic steps and ultrasmall atomic steps open up a new window for surface physics and chemistry for graphene-based as well as other two-dimensional materials. PMID:25113125

  8. 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).

  9. One-Step Model of Photoemission for Nonlocal Potentials

    NASA Astrophysics Data System (ADS)

    Potthoff, M.; Lachnitt, J.; Nolting, W.; Braun, J.

    1997-10-01

    The one-step model of valence-band photoemission and inverse photoemission from single-crystal surfaces is reformulated for generalized (nonlocal, complex and energy-dependent) potentials. Thereby, it becomes possible to account for self-energy corrections taken from many-body electronic-structure calculations. The original formulation due to Pendry and coworkers employs the KKR multiple-scattering theory for the calculation of the initial state. This prevents a straightforward generalization of the one-step model to nonlocal potentials. We therefore consider the Dyson equation which is set up within a muffin-tin-orbital representation as an alternative to obtain the initial-state Green function. This approach requires a revision of the transition-matrix elements which is carried out in detail. The final state is considered as a time-reversed LEED state as usual. The proposed generalization of the one-step model allows to distinguish between the bare photocurrent reflecting the (quasi-particle) band structure and the secondary effects due to the (dipole) selection rules and due to the wave-vector and energy dependence of the transition-matrix elements.

  10. Two-step FRET as a structural tool.

    PubMed

    Watrob, Heather M; Pan, Chia-Pin; Barkley, Mary D

    2003-06-18

    The power of FRET to study molecular complexes is expanded by the use of two or more donor/acceptor pairs. A general theoretical framework for distance measurements in three-chromophore systems is presented. Three energy transfer schemes applicable to many diverse situations are considered: (I) two-step FRET relay with FRET between the first and second chromophores and between the second and third, (II) FRET from a single donor to two different acceptors, and (III) two-step FRET relay with FRET also between the first and third chromophores. Equations for the efficiencies involving multiple energy transfer steps are derived for both donor quenching and sensitized emission measurements. The theory is supported by experimental data on model systems of known structure using steady-state donor quenching, lifetime quenching, and sensitized emission. The distances measured in the three-chromophore systems agree with those in two-chromophore systems and molecular models. Finally, labeling requirements for diagnosis of the energy transfer scheme and subsequent distance measurements are discussed.

  11. Multi-step dielectrophoresis for separation of particles.

    PubMed

    Aldaeus, Fredrik; Lin, Yuan; Amberg, Gustav; Roeraade, Johan

    2006-10-27

    A new concept for separation of particles based on repetitive dielectrophoretic trapping and release in a flow system is proposed. Calculations using the finite element method have been performed to envision the particle behavior and the separation effectiveness of the proposed method. As a model system, polystyrene beads in deionized water and a micro-flow channel with arrays of interdigited electrodes have been used. Results show that the resolution increases as a direct function of the number of trap-and-release steps, and that a difference in size will have a larger influence on the separation than a difference in other dielectrophoretic properties. About 200 trap-and-release steps would be required to separate particles with a size difference of 0.2%. The enhanced separation power of dielectrophoresis with multiple steps could be of great importance, not only for fractionation of particles with small differences in size, but also for measuring changes in surface conductivity, or for separations based on combinations of difference in size and dielectric properties.

  12. 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.

  13. 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.

  14. Stepping up, stepping back, stepping forward: Student nurses' experiences as peer mentors in a pre-nursing scholarship.

    PubMed

    Smith, Annetta; Beattie, Michelle; Kyle, Richard G

    2015-11-01

    Mentorship is an essential part of the registered nurse's role, yet few opportunities exist for student nurses to mentor others during pre-registration programmes. This paper reports student nurses' experiences of mentoring school pupils during a pre-nursing scholarship. Focus groups were conducted with fifteen final year student nurses (14 female, 1 male) in two university campuses in Scotland. Discussions were audio recorded and transcribed verbatim, and data analysed thematically. Three interconnected themes emerged: 1) stepping up; 2) stepping back; 3) stepping forward. 'Stepping up' was a process through which student nurses rapidly assumed responsibility for mentoring pupils, facilitated through the attitudes and actions of students' mentors and students' control over pupils' practice experiences. 'Stepping back' encapsulated attitudes and behaviours that enabled student nurses to mentor pupils that involved considerable judgement around how unfolding events in practice could provide learning and development opportunities, and emotional acuity to support pupils through, sometimes challenging, practice situations. 'Stepping forward' described how students' mentoring experience allowed them to appraise and affirm nursing knowledge and skills, and gain greater appreciation of the reality and complexity of mentorship in clinical practice. Peer mentoring may prepare student nurses for future mentoring roles and aid their transition into clinical practice.

  15. 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.

  16. 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…

  17. Organizing Community-Wide Dialogue for Action and Change: A Step-by-Step Guide.

    ERIC Educational Resources Information Center

    Campbell, Sarah vL.; Malick, Amy; Landesman, John; Barrett, Molly Holme; Leighninger, Matt; McCoy, Martha L.; Scully, Patrick L.

    This document is a step-by-step guide to organizing a study circle program to serve as a vehicle to achieve communitywide dialogue for action and change. Part 1 provides an overview of communitywide study circle programs, with special emphasis on their operation and impact. Part 2 details the following steps in organizing a communitywide study…

  18. Vocational Power Letters. Step-by-Step Procedures in Writing a Letter to a Legislator.

    ERIC Educational Resources Information Center

    Palladino, Dolores

    This packet for vocational educators contains information and materials on writing a letter to a state legislator. A step-by-step procedure is outlined and informative materials that expand upon the various steps are then provided. These materials include a sample Mailgram, a flowchart on how an idea becomes a state law, common sense rules for…

  19. Effects of age and step length on joint kinetics during stepping task.

    PubMed

    Bieryla, Kathleen A; Buffinton, Christine

    2015-07-16

    Following a balance perturbation, a stepping response is commonly used to regain support, and the distance of the recovery step can vary. To date, no other studies have examined joint kinetics in young and old adults during increasing step distances, when participants are required to bring their rear foot forward. Therefore, the purpose of this study was to examine age-related differences in joint kinetics with increasing step distance. Twenty young and 20 old adults completed the study. Participants completed a step starting from double support, at an initial distance equal to the individual's average step length. The distance was increased by 10% body height until an unsuccessful attempt. A one-way, repeated measures ANOVA was used to determine the effects of age on joint kinetics during the maximum step distance. A two-way, repeated measures, mixed model ANOVA was used to determine the effects of age, step distance, and their interaction on joint kinetics during the first three step distances for all participants. Young adults completed a significantly longer step than old adults. During the maximum step, in general, kinetic measures were greater in the young than in the old. As step distance increased, all but one kinetic measure increased for both young and old adults. This study has shown the ability to discriminate between young and old adults, and could potentially be used in the future to distinguish between fallers and non-fallers.

  20. 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…

  1. 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

  2. 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…

  3. Chronic variable stress exposure in male Wistar rats affects the first step of olfactory detection.

    PubMed

    Raynaud, Aurélien; Meunier, Nicolas; Acquistapace, Adrien; Bombail, Vincent

    2015-09-15

    For most animal species, olfaction plays a paramount role in their perception of the environment. Odours are initially detected in neurons located in the olfactory mucosa. This tissue is regulated by several physiological signals and can be altered in pathology. A number of clinical studies suggest an association between depressive disorders and olfactory sensory loss. In rodents, depressive-like states can be observed in models of chronic stress. We tested the hypothesis that olfactory function might be altered in a rat model of depression, induced by chronic variable stress (CVS). While CVS rats exhibited several symptoms consistent with chronic stress exposure and depressive-like states (increased sucrose intake in sucrose preference test, increased immobility in forced swim test, hyperlocomotion), their odorant responses recorded at the olfactory mucosa level by electro-olfactogram were decreased. In addition we observed increased apoptosis markers in the olfactory mucosa using Western Blot. Our data are consistent with reduced olfactory capacities in a laboratory rat model of chronic stress and depression, in agreement with human clinical data; this warrants further mechanistic studies. Furthermore, this works raises the possibility that altered olfactory function might be a confounding factor in the behavioural testing of chronically stressed or depressed rats.

  4. 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

    2016-09-07

    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.

  5. 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…

  6. 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

  7. 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

  8. Metabolic parameters for ramp versus step incremental cycle ergometer tests.

    PubMed

    Zuniga, Jorge M; Housh, Terry J; Camic, Clayton L; Bergstrom, Haley C; Traylor, Daniel A; Schmidt, Richard J; Johnson, Glen O

    2012-12-01

    The purpose of this study was to examine mean differences and the patterns of responses for oxygen uptake ([Formula: see text]O(2)), heart rate (HR), and rating of perceived exertion (RPE) for ramp (15 W·min(-1)) versus step (30 W increments every 2 min) incremental cycle ergometer tests. Fourteen subjects (age and body mass of 23.2 ± 3.1 (mean ± SD ) years and 71.1 ± 10.1 kg, respectively) visited the laboratory on separate occasions. Two-way repeated measures ANOVAs with appropriate follow-up procedures, as well as paired t tests, were used to analyze the data. In addition, polynomial regression analyses were used to determine the patterns of responses for each dependent variable for the ramp and step tests. The ramp protocol resulted in lower mean [Formula: see text]O(2) and HR values at the common power outputs than the step protocol with no differences in RPE. The increased amount of work performed during the step (total work = 75.83 kJ) versus ramp (total work = 65.60 kJ) tests at the common power outputs may have contributed to the greater [Formula: see text]O(2) and HR values. The polynomial regression analyses showed that most subjects had the same patterns of responses for the ramp and step incremental tests for HR (86%) and RPE (93%) but different patterns for [Formula: see text]O(2) (71%). The findings from the present study suggested that the protocol selection for an incremental cycle ergometer test can affect the mean values for [Formula: see text]O(2) and HR, as well as the [Formula: see text]O(2) - power output relationship.

  9. 5 CFR 838.1016 - Receipt of multiple court orders.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Receipt of multiple court orders. 838... REGULATIONS (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Affecting Civil Service Retirement Benefits § 838.1016 Receipt of multiple court orders. In the event that OPM receives two or...

  10. 5 CFR 838.1016 - Receipt of multiple court orders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Receipt of multiple court orders. 838... REGULATIONS (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Affecting Civil Service Retirement Benefits § 838.1016 Receipt of multiple court orders. In the event that OPM receives two or...

  11. 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

  12. 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.

  13. One-step multiplexed detection of foodborne pathogens: Combining a quantum dot-mediated reverse assaying strategy and magnetic separation.

    PubMed

    Yin, Binfeng; Wang, Yu; Dong, Mingling; Wu, Jing; Ran, Bei; Xie, Mengxia; Joo, Sang Woo; Chen, Yiping

    2016-12-15

    A rapid and multiplexed immunosensor was developed based on a quantum dot (QD)-reverse assaying strategy (RAS) and immuno-magnetic beads (IMBs) for one-step and simultaneous detection of Escherichia coli O157: H7 and Salmonella. In a conventional QD-based immunosensor, the fluorescence signal of the "IMBs-target-QD" immunoconjugate is directly used as the assaying readout. However, the fluorescence signal is affected by IMBs due to light scattering and the "IMBs-target-QD" immunoconjugate needs multiple washing and re-suspension steps. To address these problems, we use the surplus QD-antibody conjugate as signal readout in the RAS, which prevents interference from the IMBs, increases the fluorescence signal, and avoids complex operations. Compared with conventional QD-based immunosensor, the sensitivity of QD-RSA immunosensor for detection of Escherichia coli O157: H7 has been improved fifty-fold, and whole analysis procedure can be finished within 1h. Therefore, this RSA strategy is promising for improving the performance of QD-based immunosensors and could greatly broaden their applications.

  14. One-step multiplexed detection of foodborne pathogens: Combining a quantum dot-mediated reverse assaying strategy and magnetic separation.

    PubMed

    Yin, Binfeng; Wang, Yu; Dong, Mingling; Wu, Jing; Ran, Bei; Xie, Mengxia; Joo, Sang Woo; Chen, Yiping

    2016-12-15

    A rapid and multiplexed immunosensor was developed based on a quantum dot (QD)-reverse assaying strategy (RAS) and immuno-magnetic beads (IMBs) for one-step and simultaneous detection of Escherichia coli O157: H7 and Salmonella. In a conventional QD-based immunosensor, the fluorescence signal of the "IMBs-target-QD" immunoconjugate is directly used as the assaying readout. However, the fluorescence signal is affected by IMBs due to light scattering and the "IMBs-target-QD" immunoconjugate needs multiple washing and re-suspension steps. To address these problems, we use the surplus QD-antibody conjugate as signal readout in the RAS, which prevents interference from the IMBs, increases the fluorescence signal, and avoids complex operations. Compared with conventional QD-based immunosensor, the sensitivity of QD-RSA immunosensor for detection of Escherichia coli O157: H7 has been improved fifty-fold, and whole analysis procedure can be finished within 1h. Therefore, this RSA strategy is promising for improving the performance of QD-based immunosensors and could greatly broaden their applications. PMID:27498327

  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. Optimal time step for incompressible SPH

    NASA Astrophysics Data System (ADS)

    Violeau, Damien; Leroy, Agnès

    2015-05-01

    A classical incompressible algorithm for Smoothed Particle Hydrodynamics (ISPH) is analyzed in terms of critical time step for numerical stability. For this purpose, a theoretical linear stability analysis is conducted for unbounded homogeneous flows, leading to an analytical formula for the maximum CFL (Courant-Friedrichs-Lewy) number as a function of the Fourier number. This gives the maximum time step as a function of the fluid viscosity, the flow velocity scale and the SPH discretization size (kernel standard deviation). Importantly, the maximum CFL number at large Reynolds number appears twice smaller than with the traditional Weakly Compressible (WCSPH) approach. As a consequence, the optimal time step for ISPH is only five times larger than with WCSPH. The theory agrees very well with numerical data for two usual kernels in a 2-D periodic flow. On the other hand, numerical experiments in a plane Poiseuille flow show that the theory overestimates the maximum allowed time step for small Reynolds numbers.

  17. 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.

  18. Nine Steps to a Successful Lighting Retrofit.

    ERIC Educational Resources Information Center

    Ries, Jack

    1998-01-01

    Presents the steps needed to successfully design a lighting retrofit of school classrooms. Tips cover budgeting, technology, financing, contractor selection, assessing area function, and choosing a light source. (GR)

  19. 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 ...

  20. High-torque precision stepping drive

    NASA Technical Reports Server (NTRS)

    Kaspareck, W. E.

    1968-01-01

    Stepping drive has been designed for precise incremental angular positioning of scale models of spacecraft about a horizontal axis in order to accurately measure antenna receiving and transmitting characteristics. Positioning is insured by spring-loaded, self-locking plungers.

  1. 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:

  2. 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 ...

  3. 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)

  4. 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

  5. Five basic steps to problem trending

    NASA Technical Reports Server (NTRS)

    Bombara, Elwood L.

    1990-01-01

    Five basic steps to problem trending evolved from experience in trending problems on Space Shuttle hardware are discussed: extracting data; constructing a Pareto chart of all failure modes; constructing normalized subsystem, component, and failure-mode trend charts; identifying trend direction; and providing a summary assessment. The five-step method has been useful for identifying failure modes of concern, evaluating the effectiveness of corrective actions, and determining funding allocation.

  6. Multiple-Ring Digital Communication Network

    NASA Technical Reports Server (NTRS)

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  7. Lower limb loading in step aerobic dance.

    PubMed

    Wu, H-W; Hsieh, H-M; Chang, Y-W; Wang, L-H

    2012-11-01

    Participation in aerobic dance is associated with a number of lower extremity injuries, and abnormal joint loading seems to be a factor in these. However, information on joint loading is limited. The purpose of this study was to investigate the kinetics of the lower extremity in step aerobic dance and to compare the differences of high-impact and low-impact step aerobic dance in 4 aerobic movements (mambo, kick, L step and leg curl). 18 subjects were recruited for this study. High-impact aerobic dance requires a significantly greater range of motion, joint force and joint moment than low-impact step aerobic dance. The peak joint forces and moments in high-impact step aerobic dance were found to be 1.4 times higher than in low-impact step aerobic dance. Understanding the nature of joint loading may help choreographers develop dance combinations that are less injury-prone. Furthermore, increased knowledge about joint loading may be helpful in lowering the risk of injuries in aerobic dance instructors and students.

  8. Visual accessibility of ramps and steps.

    PubMed

    Legge, Gordon E; Yu, Deyue; Kallie, Christopher S; Bochsler, Tiana M; Gage, Rachel

    2010-01-01

    The visual accessibility of a space refers to the effectiveness with which vision can be used to travel safely through the space. For people with low vision, the detection of steps and ramps is an important component of visual accessibility. We used ramps and steps as visual targets to examine the interacting effects of lighting, object geometry, contrast, viewing distance, and spatial resolution. Wooden staging was used to construct a sidewalk with transitions to ramps or steps. Forty-eight normally sighted subjects viewed the sidewalk monocularly through acuity-reducing goggles and made recognition judgments about the presence of the ramps or steps. The effects of variation in lighting were milder than expected. Performance declined for the largest viewing distance but exhibited a surprising reversal for nearer viewing. Of relevance to pedestrian safety, the step up was more visible than the step down. We developed a probabilistic cue model to explain the pattern of target confusions. Cues determined by discontinuities in the edge contours of the sidewalk at the transition to the targets were vulnerable to changes in viewing conditions. Cues associated with the height in the picture plane of the targets were more robust.

  9. Steps in the Bacterial Flagellar Motor

    PubMed Central

    Mora, Thierry; Yu, Howard; Sowa, Yoshiyuki; Wingreen, Ned S.

    2009-01-01

    The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps. Here we propose a simple physical model, based on the storage of energy in protein springs, that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. We also predict a sublinear speed versus torque relationship for fixed load at low torque, and a peak in rotor diffusion as a function of torque. Our model provides a comprehensive framework for understanding and analyzing stepping behavior in the bacterial flagellar motor and proposes novel, testable predictions. More broadly, the storage of energy in protein springs by the flagellar motor may provide useful general insights into the design of highly efficient molecular machines. PMID:19851449

  10. Free energy of steps using atomistic simulations

    NASA Astrophysics Data System (ADS)

    Freitas, Rodrigo; Frolov, Timofey; Asta, Mark

    The properties of solid-liquid interfaces are known to play critical roles in solidification processes. Particularly special importance is given to thermodynamic quantities that describe the equilibrium state of these surfaces. For example, on the solid-liquid-vapor heteroepitaxial growth of semiconductor nanowires the crystal nucleation process on the faceted solid-liquid interface is influenced by the solid-liquid and vapor-solid interfacial free energies, and also by the free energies of associated steps at these faceted interfaces. Crystal-growth theories and mesoscale simulation methods depend on quantitative information about these properties, which are often poorly characterized from experimental measurements. In this work we propose an extension of the capillary fluctuation method for calculation of the free energy of steps on faceted crystal surfaces. From equilibrium atomistic simulations of steps on (111) surfaces of Copper we computed accurately the step free energy for different step orientations. We show that the step free energy remains finite at all temperature up to the melting point and that the results obtained agree with the more well established method of thermodynamic integration if finite size effects are taken into account. The research of RF and MA at UC Berkeley were supported by the US National Science Foundation (Grant No. DMR-1105409). TF acknowledges support through a postdoctoral fellowship from the Miller Institute for Basic Research in Science.

  11. 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.

  12. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  13. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  14. Fatigue and Multiple Sclerosis

    MedlinePlus

    Fatigue - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area ... help* daily life for: positive-mom* The National MS Society is Here to Help Need More Information? ...

  15. What Is Multiple Myeloma?

    MedlinePlus

    ... other tissues. If someone has only a single plasma cell tumor, the disease is called an isolated (or solitary ) plasmacytoma . If someone has more than one plasmacytoma, they have multiple myeloma . Multiple myeloma is ...

  16. Challenges of Parenting Multiples

    MedlinePlus

    ... Parenting Multiples There are many psychological, social, and economic issues associated with multiple pregnancies. These issues should ... births can also be helpful during difficult times. ECONOMIC ISSUES • The health care cost for delivery and ...

  17. MultipleColposcopyJCO

    Cancer.gov

    Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

  18. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by ... This Article Generic Name Select Brand Names corticotropin H.P. ACTHAR GEL epinephrine ADRENALIN Multiple Endocrine Neoplasia ...

  19. Managing Multiple Tasks in Complex, Dynamic Environments

    NASA Technical Reports Server (NTRS)

    Freed, Michael; Null, Cynthia H. (Technical Monitor)

    1998-01-01

    Sketchy planners are designed to achieve goals in realistically complex, time-pressured, and uncertain task environments. However, the ability to manage multiple, potentially interacting tasks in such environments requires extensions to the functionality these systems typically provide. This paper identifies a number of factors affecting how interacting tasks should be prioritized, interrupted, and resumed, and then describes a sketchy planner called APEX that takes account of these factors when managing multiple tasks.

  20. Thermal sensation and thermophysiological responses to metabolic step-changes

    NASA Astrophysics Data System (ADS)

    Goto, T.; Toftum, J.; de Dear, R.; Fanger, P. O.

    2006-05-01

    This study investigated the effect on thermal perception and thermophysiological variables of controlled metabolic excursions of various intensities and durations. Twenty-four subjects were alternately seated on a chair or exercised by walking on a treadmill at a temperature predicted to be neutral at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise or decline immediately (within 1 min) after a change of activity, which means that even moderate activity changes of short duration affect thermal perceptions of humans. After approximately 15 20 min under constant activity, subjective thermal responses approximated the steady-state response. The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative average metabolic rate with varying activity levels, e.g. for the prediction of thermal sensation by steady-state comfort models. The activity during the most recent 5 min should be weighted 65%, during the prior 10 5 min 25% and during the prior 20 10 min 10%.