A Three-Step Synthesis of Benzoyl Peroxide

ERIC Educational Resources Information Center

Her, Brenda; Jones, Alexandra; Wollack, James W.

2014-01-01

Benzoyl peroxide is used as a bleaching agent for flour and whey processing, a polymerization initiator in the synthesis of plastics, and the active component of acne medication. Because of its simplicity and wide application, benzoyl peroxide is a target molecule of interest. It can be affordably synthesized in three steps from bromobenzene using…

From N-triisopropylsilylpyrrole to an optically active C-4 substituted pyroglutamic acid: total synthesis of penmacric acid.

PubMed

Berini, Christophe; Pelloux-Léon, Nadia; Minassian, Frédéric; Denis, Jean-Noël

2009-11-07

The stereoselective synthesis of penmacric acid, an optically active C-4 substituted pyroglutamic acid, has been efficiently achieved through an unusual 11-step sequence starting from simple N-triisopropylsilylpyrrole. The key-steps are the initial addition of the pyrrole nucleus onto a chiral nitrone and the obtention of the pyroglutamic acid moiety by reductive hydrogenation of the pyrrole followed by oxidation of the corresponding pyrrolidine into pyrrolidinone.

Ligand-accelerated activation of strong C-H bonds of alkanes by a (salen)ruthenium(VI)-nitrido complex.

PubMed

Man, Wai-Lun; Lam, William W Y; Kwong, Hoi-Ki; Yiu, Shek-Man; Lau, Tai-Chu

2012-09-03

Kinetic and mechanistic studies on the intermolecular activation of strong C-H bonds of alkanes by a (salen)ruthenium(VI) nitride were performed. The initial, rate-limiting step, the hydrogen atom transfer (HAT) from the alkane to Ru(VI)≡N, generates Ru(V)=NH and RC·HCH(2)R. The following steps involve N-rebound and desaturation. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Planning activity for internally generated reward goals in monkey amygdala neurons

PubMed Central

Schultz, Wolfram

2015-01-01

The best rewards are often distant and can only be achieved by planning and decision-making over several steps. We designed a multi-step choice task in which monkeys followed internal plans to save rewards towards self-defined goals. During this self-controlled behavior, amygdala neurons showed future-oriented activity that reflected the animal’s plan to obtain specific rewards several trials ahead. This prospective activity encoded crucial components of the animal’s plan, including value and length of the planned choice sequence. It began on initial trials when a plan would be formed, reappeared step-by-step until reward receipt, and readily updated with a new sequence. It predicted performance, including errors, and typically disappeared during instructed behavior. Such prospective activity could underlie the formation and pursuit of internal plans characteristic for goal-directed behavior. The existence of neuronal planning activity in the amygdala suggests an important role for this structure in guiding behavior towards internally generated, distant goals. PMID:25622146

Coordination of rapid stepping with arm pointing: anticipatory changes and step adaptation.

PubMed

Yiou, Eric; Schneider, Cyril; Roussel, Didier

2007-06-01

The present study explored whether rapid stepping is influenced by the coordination of an arm pointing task. Nine participants were instructed to (a) point the index finger of the dominant arm towards a target from the standing posture, (b) initiate a rapid forward step with the contralateral leg, and (c) synchronize stepping and pointing (combined task). Force plate and ankle muscle electromyography (EMG) recordings were contrasted between (b) and (c). In the combined task, the arm acceleration trace most often peaked around foot-off, coinciding with a 15% increase in the forward acceleration of the center of gravity (CoG). Backward displacement of the center of foot pressure at foot-off, duration of anticipatory postural adjustments (APAs) and ankle muscle EMG activity remained unchanged. In contrast, durations of swing phase and whole step were reduced and step length was smaller in the combined task. A reduction in the swing phase was correlated with an increased CoG forward acceleration at foot-off. Changes in the biomechanics of step initiation during the combined task might be ascribed to the postural dynamics elicited by arm pointing, and not to a modulation of the step APAs programming.

A Coordinated Initialization Process for the Distributed Space Exploration Simulation

NASA Technical Reports Server (NTRS)

Crues, Edwin Z.; Phillips, Robert G.; Dexter, Dan; Hasan, David

2007-01-01

A viewgraph presentation on the federate initialization process for the Distributed Space Exploration Simulation (DSES) is described. The topics include: 1) Background: DSES; 2) Simulation requirements; 3) Nine Step Initialization; 4) Step 1: Create the Federation; 5) Step 2: Publish and Subscribe; 6) Step 3: Create Object Instances; 7) Step 4: Confirm All Federates Have Joined; 8) Step 5: Achieve initialize Synchronization Point; 9) Step 6: Update Object Instances With Initial Data; 10) Step 7: Wait for Object Reflections; 11) Step 8: Set Up Time Management; 12) Step 9: Achieve startup Synchronization Point; and 13) Conclusions

The roles of prefrontal and posterior parietal cortex in algebra problem solving: a case of using cognitive modeling to inform neuroimaging data.

PubMed

Danker, Jared F; Anderson, John R

2007-04-15

In naturalistic algebra problem solving, the cognitive processes of representation and retrieval are typically confounded, in that transformations of the equations typically require retrieval of mathematical facts. Previous work using cognitive modeling has associated activity in the prefrontal cortex with the retrieval demands of algebra problems and activity in the posterior parietal cortex with the transformational demands of algebra problems, but these regions tend to behave similarly in response to task manipulations (Anderson, J.R., Qin, Y., Sohn, M.-H., Stenger, V.A., Carter, C.S., 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261; Qin, Y., Carter, C.S., Silk, E.M., Stenger, A., Fissell, K., Goode, A., Anderson, J.R., 2004. The change of brain activation patterns as children learn algebra equation solving. Proc. Natl. Acad. Sci. 101, 5686-5691). With this study we attempt to isolate activity in these two regions by using a multi-step algebra task in which transformation (parietal) is manipulated in the first step and retrieval (prefrontal) is manipulated in the second step. Counter to our initial predictions, both brain regions were differentially active during both steps. We designed two cognitive models, one encompassing our initial assumptions and one in which both processes were engaged during both steps. The first model provided a poor fit to the behavioral and neural data, while the second model fit both well. This simultaneously emphasizes the strong relationship between retrieval and representation in mathematical reasoning and demonstrates that cognitive modeling can serve as a useful tool for understanding task manipulations in neuroimaging experiments.

Simulation Activity for Initiating Thinking about Year Around School Plans.

ERIC Educational Resources Information Center

Sagness, Richard L.

This document presents a three-step model for providing teachers with basic information on year-round or extended school plans. As a first step, descriptions of basic plans are given. The four used in this paper are Staggered Quarter for All, Full 48-week School Year for All, Voluntary Summer Program, and A Summer Program for Professional…

More realistic power estimation for new user, active comparator studies: an empirical example.

PubMed

Gokhale, Mugdha; Buse, John B; Pate, Virginia; Marquis, M Alison; Stürmer, Til

2016-04-01

Pharmacoepidemiologic studies are often expected to be sufficiently powered to study rare outcomes, but there is sequential loss of power with implementation of study design options minimizing bias. We illustrate this using a study comparing pancreatic cancer incidence after initiating dipeptidyl-peptidase-4 inhibitors (DPP-4i) versus thiazolidinediones or sulfonylureas. We identified Medicare beneficiaries with at least one claim of DPP-4i or comparators during 2007-2009 and then applied the following steps: (i) exclude prevalent users, (ii) require a second prescription of same drug, (iii) exclude prevalent cancers, (iv) exclude patients age <66 years and (v) censor for treatment changes during follow-up. Power to detect hazard ratios (effect measure strongly driven by the number of events) ≥ 2.0 estimated after step 5 was compared with the naïve power estimated prior to step 1. There were 19,388 and 28,846 DPP-4i and thiazolidinedione initiators during 2007-2009. The number of drug initiators dropped most after requiring a second prescription, outcomes dropped most after excluding patients with prevalent cancer and person-time dropped most after requiring a second prescription and as-treated censoring. The naïve power (>99%) was considerably higher than the power obtained after the final step (~75%). In designing new-user active-comparator studies, one should be mindful how steps minimizing bias affect sample-size, number of outcomes and person-time. While actual numbers will depend on specific settings, application of generic losses in percentages will improve estimates of power compared with the naive approach mostly ignoring steps taken to increase validity. Copyright © 2015 John Wiley & Sons, Ltd.

Effectiveness of an Activity Tracker- and Internet-Based Adaptive Walking Program for Adults: A Randomized Controlled Trial.

PubMed

Poirier, Josée; Bennett, Wendy L; Jerome, Gerald J; Shah, Nina G; Lazo, Mariana; Yeh, Hsin-Chieh; Clark, Jeanne M; Cobb, Nathan K

2016-02-09

The benefits of physical activity are well documented, but scalable programs to promote activity are needed. Interventions that assign tailored and dynamically adjusting goals could effect significant increases in physical activity but have not yet been implemented at scale. Our aim was to examine the effectiveness of an open access, Internet-based walking program that assigns daily step goals tailored to each participant. A two-arm, pragmatic randomized controlled trial compared the intervention to no treatment. Participants were recruited from a workplace setting and randomized to a no-treatment control (n=133) or to treatment (n=132). Treatment participants received a free wireless activity tracker and enrolled in the walking program, Walkadoo. Assessments were fully automated: activity tracker recorded primary outcomes (steps) without intervention by the participant or investigators. The two arms were compared on change in steps per day from baseline to follow-up (after 6 weeks of treatment) using a two-tailed independent samples t test. Participants (N=265) were 66.0% (175/265) female with an average age of 39.9 years. Over half of the participants (142/265, 53.6%) were sedentary (<5000 steps/day) and 44.9% (119/265) were low to somewhat active (5000-9999 steps/day). The intervention group significantly increased their steps by 970 steps/day over control (P<.001), with treatment effects observed in sedentary (P=.04) and low-to-somewhat active (P=.004) participants alike. The program is effective in increasing daily steps. Participants benefited from the program regardless of their initial activity level. A tailored, adaptive approach using wireless activity trackers is realistically implementable and scalable. Clinicaltrials.gov NCT02229409, https://clinicaltrials.gov/ct2/show/NCT02229409 (Archived by WebCite at http://www.webcitation.org/6eiWCvBYe).

Effect of growth pressure on the morphology evolution and doping characteristics in nonpolar a-plane GaN

NASA Astrophysics Data System (ADS)

Song, Keun Man; Kim, Jong Min; Kang, Bong Kyun; Shin, Chan Soo; Ko, Chul Gi; Kong, Bo Hyun; Cho, Hyung Koun; Yoon, Dae Ho; Kim, Hogyoung; Hwang, Sung Min

2012-02-01

Nonpolar a-plane GaN layers grown on r-plane sapphire substrates were examined by using a two-step growth process. The higher initial growth pressure for the nucleation layer resulted in the improved crystalline quality with lower density of both threading dislocations and basal stacking faults. This was attributed to the higher degree of initial roughening and recovery time via a growth mode transition from three-dimensional (3D) to quasi two-dimensional (2D) lateral growth. Using Hall-effect measurements, the overgrown Si doped GaN layers grown with higher initial growth pressure were found to have higher mobility. The scattering mechanism due to the dislocations was dominant especially at low temperature (<200 K) for the lower initial growth pressure, which was insignificant for the higher initial growth pressure. The temperature-dependent Hall-effect measurements for the Mg doped GaN with a higher initial growth pressure yielded the activation energy and the acceptor concentration to be 128 meV and 1.2 × 1019 cm-3, respectively, corresponding to about 3.6% of activation at room temperature. Two-step growth scheme with a higher initial growth pressure is suggested as a potential method to improve the performance of nonpolar a-plane GaN based devices.

Foot Placement Characteristics and Plantar Pressure Distribution Patterns during Stepping on Ground in Neonates

PubMed Central

Sylos-Labini, F.; Magnani, S.; Cappellini, G.; La Scaleia, V.; Fabiano, A.; Picone, S.; Paolillo, P.; Di Paolo, A.; Lacquaniti, F.; Ivanenko, Y.

2017-01-01

Stepping on ground can be evoked in human neonates, though it is rather irregular and stereotyped heel-to-toe roll-over pattern is lacking. Such investigations can provide insights into the role of contact- or load-related proprioceptive feedback during early development of locomotion. However, the detailed characteristics of foot placements and their association with motor patterns are still incompletely documented. We elicited stepping in 33 neonates supported on a table. Unilateral limb kinematics, bilateral plantar pressure distribution and EMG activity from up to 11 ipsilateral leg muscles were recorded. Foot placement characteristics in neonates showed a wide variation. In ~25% of steps, the swinging foot stepped onto the contralateral foot due to generally small step width. In the remaining steps with separate foot placements, the stance phase could start with forefoot (28%), midfoot (47%), or heel (25%) touchdowns. Despite forefoot or heel initial contacts, the kinematic and loading patterns markedly differed relatively to toe-walking or adult-like two-peaked vertical force profile. Furthermore, while the general stepping parameters (cycle duration, step length, range of motion of proximal joints) were similar, the initial foot contact was consistently associated with specific center-of-pressure excursion, range of motion in the ankle joint, and the center-of-activity of extensor muscles (being shifted by ~5% of cycle toward the end of stance in the “heel” relative to “forefoot” condition). In sum, we found a variety of footfall patterns in conjunction with associated changes in motor patterns. These findings suggest the potential contribution of load-related proprioceptive feedback and/or the expression of variations in the locomotor program already during early manifestations of stepping on ground in human babies. PMID:29066982

Unprecedented covalently attached ATRP initiator onto OH-functionalized mica surfaces.

PubMed

Lego, Béatrice; Skene, W G; Giasson, Suzanne

2008-01-15

Mica substrates were activated by a plasma method leading to OH-functionalized surfaces to which an atom transfer radical polymerization (ATRP) radical initiator was covalently bound using standard siloxane protocols. The unprecedented covalently immobilized initiator underwent radical polymerization with tert-butyl acrylate, yielding for the first time end-grafted polymer brushes that are covalently linked to mica. The initiator grafting on the mica substrate was confirmed by time-of-flight secondary ion mass spectrometry (TOF-SIMS), while the change in the water contact angle of the OH-activated mica surface was used to follow the change in surface coverage of the initiator on the surface. The polymer brush and initiator film thicknesses relative to the virgin mica were confirmed by atomic force microscopy (AFM). This was done by comparing the atomic step-height difference between a protected area of freshly cleaved mica and a zone exposed to plasma activation, initiator immobilization, and then ATRP.

Observation of incomplete drainage of a branched negative stepped leader system during the initial return stroke, and its implications

NASA Astrophysics Data System (ADS)

Petersen, D.; Beasley, W. H.

2012-12-01

We present high-speed video, taken at 75,000 frames per second, of an anomalous lightning flash that involved two distinct return strokes from different branches of the same branched negative stepped leader system. During the initial return stroke the leader system was incompletely drained, resulting in the continued development of a large side branch. The upper portions of this side branch exhibited a pulse of luminosity during the initial return stroke, but the luminosity did not extend down the branch. The lower portion of the branch continued to develop downward as a negative stepped leader, but at a much slower velocity. Continued stepping activity was observed in this branch as it continued downward at a significantly reduced velocity, finally attaching to the earth 1.8 milliseconds after the main return stroke. The ensuing return stroke was characterized by a slower vertical velocity and weaker luminous pulse. Based on this observation, we coin the term "orphaned branch" to describe a branch of a leader system that is not drained during a return stroke. While our case involves a branch that eventually connected to the ground and produced a return stroke, we also consider the possibility that such branches may also simply cease to progress and effectively deposit large amounts of space charge near their extremities. Such space charge would have a strong influence on subsequent breakdown activity in their vicinity, such as shielding subsequent descending negative stepped leaders or triggering upward positive leaders from earth's surface.

By counteracting gravity, triceps surae sets both kinematics and kinetics of gait

PubMed Central

Honeine, Jean‐Louis; Schieppati, Marco; Gagey, Oliver; Do, Manh‐Cuong

2014-01-01

Abstract In the single‐stance phase of gait, gravity acting on the center of mass (CoM) causes a disequilibrium torque, which generates propulsive force. Triceps surae activity resists gravity by restraining forward tibial rotation thereby tuning CoM momentum. We hypothesized that time and amplitude modulation of triceps surae activity determines the kinematics (step length and cadence) and kinetics of gait. Nineteen young subjects participated in two experiments. In the gait initiation (GI) protocol, subjects deliberately initiated walking at different velocities for the same step length. In the balance‐recovery (BR) protocol, subjects executed steps of different length after being unexpectedly released from an inclined posture. Ground reaction force was recorded by a large force platform and electromyography of soleus, gastrocnemius medialis and lateralis, and tibialis anterior muscles was collected by wireless surface electrodes. In both protocols, the duration of triceps activity was highly correlated with single‐stance duration (GI, R2 = 0.68; BR, R2 = 0.91). In turn, step length was highly correlated with single‐stance duration (BR, R2 = 0.70). Control of CoM momentum was obtained by decelerating the CoM fall via modulation of amplitude of triceps activity. By modulation of triceps activity, the central nervous system (CNS) varied the position of CoM with respect to the center of pressure (CoP). The CoM‐CoP gap in the sagittal plane was determinant for setting the disequilibrium torque and thus walking velocity. Thus, by controlling the gap, CNS‐modified walking velocity (GI, R2 = 0.86; BR, R2 = 0.92). This study is the first to highlight that by merely counteracting gravity, triceps activity sets the kinematics and kinetics of gait. It also provides evidence that the surge in triceps activity during fast walking is due to the increased requirement of braking the fall of CoM in late stance in order to perform a smoother step‐to‐step transition. PMID:24744898

Thigh Muscle Activity, Knee Motion, and Impact Force During Side-Step Pivoting in Agility-Trained Female Basketball Players

PubMed Central

Wilderman, Danielle R; Ross, Scott E; Padua, Darin A

2009-01-01

Context: Improving neuromuscular control of hamstrings muscles might have implications for decreasing anterior cruciate ligament injuries in females. Objective: To examine the effects of a 6-week agility training program on quadriceps and hamstrings muscle activation, knee flexion angles, and peak vertical ground reaction force. Design: Prospective, randomized clinical research trial. Setting: Sports medicine research laboratory. Patients or Other Participants: Thirty female intramural basketball players with no history of knee injury (age  =  21.07 ± 2.82 years, height  =  171.27 ± 4.66 cm, mass  =  66.36 ± 7.41 kg). Intervention(s): Participants were assigned to an agility training group or a control group that did not participate in agility training. Participants in the agility training group trained 4 times per week for 6 weeks. Main Outcome Measure(s): We used surface electromyography to assess muscle activation for the rectus femoris, vastus medialis oblique, medial hamstrings, and lateral hamstrings for 50 milliseconds before initial ground contact and while the foot was in contact with the ground during a side-step pivot maneuver. Knee flexion angles (at initial ground contact, maximum knee flexion, knee flexion displacement) and peak vertical ground reaction force also were assessed during this maneuver. Results: Participants in the training group increased medial hamstrings activation during ground contact after the 6-week agility training program. Both groups decreased their vastus medialis oblique muscle activation during ground contact. Knee flexion angles and peak vertical ground reaction force did not change for either group. Conclusions: Agility training improved medial hamstrings activity in female intramural basketball players during a side-step pivot maneuver. Agility training that improves hamstrings activity might have implications for reducing anterior cruciate ligament sprain injury associated with side-step pivots. PMID:19180214

Combining Fast-Walking Training and a Step Activity Monitoring Program to Improve Daily Walking Activity After Stroke: A Preliminary Study.

PubMed

Danks, Kelly A; Pohlig, Ryan; Reisman, Darcy S

2016-09-01

To determine preliminary efficacy and to identify baseline characteristics predicting who would benefit most from fast walking training plus a step activity monitoring program (FAST+SAM) compared with fast walking training (FAST) alone in persons with chronic stroke. Randomized controlled trial with blinded assessors. Outpatient clinical research laboratory. Individuals (N=37) >6 months poststroke. Subjects were assigned to either FAST, which was walking training at their fastest possible speed on the treadmill (30min) and overground 3 times per week for 12 weeks, or FAST+SAM. The step activity monitoring program consisted of daily step monitoring with an activity monitor, goal setting, and identification of barriers to activity and strategies to overcome barriers. Daily step activity metrics (steps/day [SPD], time walking per day), walking speed, and 6-minute walk test (6MWT) distance. There was a significant effect of time for both groups, with all outcomes improving from pre- to posttraining (all P values <.05). The FAST+SAM was superior to FAST for 6MWT (P=.018), with a larger increase in the FAST+SAM group. The interventions had differential effectiveness based on baseline step activity. Sequential moderated regression models demonstrated that for subjects with baseline levels of step activity and 6MWT distances that were below the mean, the FAST+SAM intervention was more effective than FAST (1715±1584 vs 254±933 SPD; P<.05 for overall model and ΔR(2) for SPD and 6MWT). The addition of a step activity monitoring program to a fast walking training intervention may be most effective in persons with chronic stroke who have initial low levels of walking endurance and activity. Regardless of baseline performance, the FAST+SAM intervention was more effective for improving walking endurance. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Escherichia coli Ribosomal Protein S1 Unfolds Structured mRNAs Onto the Ribosome for Active Translation Initiation

PubMed Central

Duval, Mélodie; Korepanov, Alexey; Fuchsbauer, Olivier; Fechter, Pierre; Haller, Andrea; Fabbretti, Attilio; Choulier, Laurence; Micura, Ronald; Klaholz, Bruno P.; Romby, Pascale; Springer, Mathias; Marzi, Stefano

2013-01-01

Regulation of translation initiation is well appropriate to adapt cell growth in response to stress and environmental changes. Many bacterial mRNAs adopt structures in their 5′ untranslated regions that modulate the accessibility of the 30S ribosomal subunit. Structured mRNAs interact with the 30S in a two-step process where the docking of a folded mRNA precedes an accommodation step. Here, we used a combination of experimental approaches in vitro (kinetic of mRNA unfolding and binding experiments to analyze mRNA–protein or mRNA–ribosome complexes, toeprinting assays to follow the formation of ribosomal initiation complexes) and in vivo (genetic) to monitor the action of ribosomal protein S1 on the initiation of structured and regulated mRNAs. We demonstrate that r-protein S1 endows the 30S with an RNA chaperone activity that is essential for the docking and the unfolding of structured mRNAs, and for the correct positioning of the initiation codon inside the decoding channel. The first three OB-fold domains of S1 retain all its activities (mRNA and 30S binding, RNA melting activity) on the 30S subunit. S1 is not required for all mRNAs and acts differently on mRNAs according to the signals present at their 5′ ends. This work shows that S1 confers to the ribosome dynamic properties to initiate translation of a large set of mRNAs with diverse structural features. PMID:24339747

Rigid Ankle Foot Orthosis Deteriorates Mediolateral Balance Control and Vertical Braking during Gait Initiation

PubMed Central

Delafontaine, Arnaud; Gagey, Olivier; Colnaghi, Silvia; Do, Manh-Cuong; Honeine, Jean-Louis

2017-01-01

Rigid ankle-foot orthoses (AFO) are commonly used for impeding foot drop during the swing phase of gait. They also reduce pain and improve gait kinematics in patients with weakness or loss of integrity of ankle-foot complex structures due to various pathological conditions. However, this comes at the price of constraining ankle joint mobility, which might affect propulsive force generation and balance control. The present study examined the effects of wearing an AFO on biomechanical variables and electromyographic activity of tibialis anterior (TA) and soleus muscles during gait initiation (GI). Nineteen healthy adults participated in the study. They initiated gait at a self-paced speed with no ankle constraint as well as wearing an AFO on the stance leg, or bilaterally. Constraining the stance leg ankle decreased TA activity ipsilaterally during the anticipatory postural adjustment (APA) of GI, and ipsilateral soleus activity during step execution. In the sagittal plane, the decrease in the stance leg TA activity reduced the backward displacement of the center of pressure (CoP) resulting in a reduction of the forward velocity of the center of mass (CoM) measured at foot contact (FC). In the frontal plane, wearing the AFO reduced the displacement of the CoP in the direction of the swing leg during the APA phase. The mediolateral velocity of the CoM increased during single-stance prompting a larger step width to recover balance. During step execution, the CoM vertical downward velocity is normally reduced in order to lessen the impact of the swing leg with the floor and facilitates the rise of the CoM that occurs during the subsequent double-support phase. The reduction in stance leg soleus activity caused by constraining the ankle weakened the vertical braking of the CoM during step execution. This caused the absolute instantaneous vertical velocity of the CoM at FC to be greater in the constrained conditions with respect to the control condition. From a rehabilitation perspective, passively- or actively-powered assistive AFOs could correct for the reduction in muscle activity and enhance balance control during GI of patients. PMID:28503144

An Initial Look at DoD’s Activities Toward Climate Change Resiliency: An Annotated Bibliography

DTIC Science & Technology

2016-02-01

Draft Working Paper An Initial Look at DoD’s Activities Toward Climate Change Resiliency An Annotated Bibliography Susan A. Resetar and Neil Berg...contribute www.rand.org iii Preface The global effects of climate change could have widespread effects and thus pose concerns for all governments...effects and consider possible responses. Many elements of the Department have taken steps to begin dealing with the implications of climate change

Methodology for the specification of communication activities within the framework of a multi-layered architecture: Toward the definition of a knowledge base

NASA Astrophysics Data System (ADS)

Amyay, Omar

A method defined in terms of synthesis and verification steps is presented. The specification of the services and protocols of communication within a multilayered architecture of the Open Systems Interconnection (OSI) type is an essential issue for the design of computer networks. The aim is to obtain an operational specification of the protocol service couple of a given layer. Planning synthesis and verification steps constitute a specification trajectory. The latter is based on the progressive integration of the 'initial data' constraints and verification of the specification originating from each synthesis step, through validity constraints that characterize an admissible solution. Two types of trajectories are proposed according to the style of the initial specification of the service protocol couple: operational type and service supplier viewpoint; knowledge property oriented type and service viewpoint. Synthesis and verification activities were developed and formalized in terms of labeled transition systems, temporal logic and epistemic logic. The originality of the second specification trajectory and the use of the epistemic logic are shown. An 'artificial intelligence' approach enables a conceptual model to be defined for a knowledge base system for implementing the method proposed. It is structured in three levels of representation of the knowledge relating to the domain, the reasoning characterizing synthesis and verification activities and the planning of the steps of a specification trajectory.

Description of bioremediation of soils using the model of a multistep system of microorganisms

NASA Astrophysics Data System (ADS)

Lubysheva, A. I.; Potashev, K. A.; Sofinskaya, O. A.

2018-01-01

The paper deals with the development of a mathematical model describing the interaction of a multi-step system of microorganisms in soil polluted with oil products. Each step in this system uses products of vital activity of the previous step to feed. Six different models of the multi-step system are considered. The equipping of the models with coefficients was carried out from the condition of minimizing the residual of the calculated and experimental data using an original algorithm based on the Levenberg-Marquardt method in combination with the Monte Carlo method for the initial approximation finding.

Maintenance of lateral stability during standing and walking in the cat.

PubMed

Karayannidou, A; Zelenin, P V; Orlovsky, G N; Sirota, M G; Beloozerova, I N; Deliagina, T G

2009-01-01

During free behaviors animals often experience lateral forces, such as collisions with obstacles or interactions with other animals. We studied postural reactions to lateral pulses of force (pushes) in the cat during standing and walking. During standing, a push applied to the hip region caused a lateral deviation of the caudal trunk, followed by a return to the initial position. The corrective hindlimb electromyographic (EMG) pattern included an initial wave of excitation in most extensors of the hindlimb contralateral to push and inhibition of those in the ipsilateral limb. In cats walking on a treadmill with only hindlimbs, application of force also caused lateral deviation of the caudal trunk, with subsequent return to the initial position. The type of corrective movement depended on the pulse timing relative to the step cycle. If the force was applied at the end of the stance phase of one of the limbs or during its swing phase, a lateral component appeared in the swing trajectory of this limb. The corrective step was directed either inward (when the corrective limb was ipsilateral to force application) or outward (when it was contralateral). The EMG pattern in the corrective limb was characterized by considerable modification of the hip abductor and adductor activity in the perturbed step. Thus the basic mechanisms for balance control in these two forms of behavior are different. They perform a redistribution of muscle activity between symmetrical limbs (in standing) and a reconfiguration of the base of support during a corrective lateral step (in walking).

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease.

PubMed

Alahmari, Ayedh D; Patel, Anant R C; Kowlessar, Beverly S; Mackay, Alex J; Singh, Richa; Wedzicha, Jadwiga A; Donaldson, Gavin C

2014-06-02

During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time.

Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

PubMed

Christiansen, Cory; Moore, Charity; Schenkman, Margaret; Kluger, Benzi; Kohrt, Wendy; Delitto, Anthony; Berman, Brian; Hall, Deborah; Josbeno, Deborah; Poon, Cynthia; Robichaud, Julie; Wellington, Toby; Jain, Samay; Comella, Cynthia; Corcos, Daniel; Melanson, Ed

2017-04-01

Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

Ischemic postconditioning: from receptor to end-effector.

PubMed

Cohen, Michael V; Downey, James M

2011-03-01

Ischemic preconditioning, a robust cardioprotective intervention, has limited clinical efficacy because it must be initiated before myocardial ischemia. Conversely, ischemic postconditioning, repeated brief reocclusions of a coronary artery after release of prolonged coronary occlusion, provides cardioprotection in clinically feasible settings, that is, coronary angioplasty. Ischemic postconditioning's signaling is being investigated to identify pharmacological triggers that could be used without angioplasty. In initial minutes of reperfusion H(+) washes out of previously ischemic cells. pH rises enabling mitochondrial permeability transition pores (MPTPs) to form leading to cessation of ATP production and cell necrosis. Coronary reocclusions maintain sufficient acidosis to keep MPTP closed while signaling is initiated that can generate endogenous antagonists of MPTP formation even after cellular pH normalizes. Reintroduction of oxygen generates reactive oxygen species that activate protein kinase C to increase sensitivity of adenosine A(2b) receptors allowing adenosine released from ischemic cells to bind leading to activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2. Phosphatidylinositol 3-kinase activation results in phosphorylation of Akt promoting activation of nitric oxide synthase and nitric oxide production, which inhibits glycogen synthase kinase-3β, perhaps the final cytosolic signaling step before inhibition of MPTP formation. Interference with MPTP may be the final step that determines cell salvage.

Neural control of visual search by frontal eye field: effects of unexpected target displacement on visual selection and saccade preparation.

PubMed

Murthy, Aditya; Ray, Supriya; Shorter, Stephanie M; Schall, Jeffrey D; Thompson, Kirk G

2009-05-01

The dynamics of visual selection and saccade preparation by the frontal eye field was investigated in macaque monkeys performing a search-step task combining the classic double-step saccade task with visual search. Reward was earned for producing a saccade to a color singleton. On random trials the target and one distractor swapped locations before the saccade and monkeys were rewarded for shifting gaze to the new singleton location. A race model accounts for the probabilities and latencies of saccades to the initial and final singleton locations and provides a measure of the duration of a covert compensation process-target-step reaction time. When the target stepped out of a movement field, noncompensated saccades to the original location were produced when movement-related activity grew rapidly to a threshold. Compensated saccades to the final location were produced when the growth of the original movement-related activity was interrupted within target-step reaction time and was replaced by activation of other neurons producing the compensated saccade. When the target stepped into a receptive field, visual neurons selected the new target location regardless of the monkeys' response. When the target stepped out of a receptive field most visual neurons maintained the representation of the original target location, but a minority of visual neurons showed reduced activity. Chronometric analyses of the neural responses to the target step revealed that the modulation of visually responsive neurons and movement-related neurons occurred early enough to shift attention and saccade preparation from the old to the new target location. These findings indicate that visual activity in the frontal eye field signals the location of targets for orienting, whereas movement-related activity instantiates saccade preparation.

H 2 Desorption from MgH 2 Surfaces with Steps and Catalyst-Dopants

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

Reich, Jason M.; Wang, Lin-Lin; Johnson, Duane D.

2014-03-10

Light-metal hydrides, like MgH 2, remain under scrutiny as prototypes for reversible H-storage materials. For MgH 2, we assess hydrogen desorption/adsorption properties (enthalpy and kinetic barriers) for stepped, catalyst-doped surfaces occurring, e.g., from ball-milling in real samples. Employing density functional theory and simulated annealing in a slab model, we studied initial H 2 desorption from stepped surfaces with(out) titanium (Ti) catalytic dopant. Extensive simulated annealing studies were performed to find the dopant’s site preferences. For the most stable initial and final (possibly magnetic) states, nudged elastic band (NEB) calculations were performed to determine the H 2-desorption activation energy. We usedmore » a moment-transition NEB method to account for the dopant’s transition to the lowest-energy magnetic state at each image along the band. We identify a dopant-related surface-desorption mechanism that reloads via bulk H diffusion. While reproducing the observed bulk enthalpy of desorption, we find a decrease of 0.24 eV (a 14% reduction) in the activation energy on doped stepped surface; together with a 22% reduction on a doped flat surface, this brackets the assessed 18% reduction in kinetic barrier for ball-milled MgH 2 samples with low concentration of Ti from experiment.« less

A kinetic model of the formation of organic monolayers on hydrogen-terminated silicon by hydrosilation of alkenes.

PubMed

Woods, M; Carlsson, S; Hong, Q; Patole, S N; Lie, L H; Houlton, A; Horrocks, B R

2005-12-22

We have analyzed a kinetic model for the formation of organic monolayers based on a previously suggested free radical chain mechanism for the reaction of unsaturated molecules with hydrogen-terminated silicon surfaces (Linford, M. R.; Fenter, P. M.; Chidsey, C. E. D. J. Am. Chem. Soc 1995, 117, 3145). A direct consequence of this mechanism is the nonexponential growth of the monolayer, and this has been observed spectroscopically. In the model, the initiation of silyl radicals on the surface is pseudo first order with rate constant, ki, and the rate of propagation is determined by the concentration of radicals and unreacted Si-H nearest neighbor sites with a rate constant, kp. This propagation step determines the rate at which the monolayer forms by addition of alkene molecules to form a track of molecules that constitute a self-avoiding random walk on the surface. The initiation step describes how frequently new random walks commence. A termination step by which the radicals are destroyed is also included. The solution of the kinetic equations yields the fraction of alkylated surface sites and the mean length of the random walks as a function of time. In mean-field approximation we show that (1) the average length of the random walk is proportional to (kp/ki)1/2, (2) the monolayer surface coverage grows exponentially only after an induction period, (3) the effective first-order rate constant describing the growth of the monolayer and the induction period (kt) is k = (2ki kp)1/2, (4) at long times the effective first-order rate constant drops to ki, and (5) the overall activation energy for the growth kinetics is the mean of the activation energies for the initiation and propagation steps. Monte Carlo simulations of the mechanism produce qualitatively similar kinetic plots, but the mean random walk length (and effective rate constant) is overestimated by the mean field approximation and when kp > ki, we find k approximately ki0.7kp0.3 and Ea = (0.7Ei+ 0.3Ep). However the most striking prediction of the Monte Carlo simulations is that at long times, t > 1/k, the effective first-order rate constant decreases to ki even in the absence of a chemical termination step. Experimental kinetic data for the reaction of undec-1-ene with hydrogen-terminated porous silicon under thermal reflux in toluene and ethylbenzene gave a value of k = 0.06 min(-1) and an activation energy of 107 kJ mol(-1). The activation energy is in reasonable agreement with density functional calculations of the transition state energies for the initiation and propagation steps.

Binge Drinking in Female College Students: The Association of Physical Activity, Weight Concern, and Depressive Symptoms.

ERIC Educational Resources Information Center

Vickers, Kristin S.; Patten, Christi A.; Bronars, Carrie; Lane, Kristi; Stevens, Susanna R.; Croghan, Ivana T.; Schroeder, Darrell R.; Clark, Matthew M.

2004-01-01

As an initial step in building gender-specific binge drinking intervention programs, the authors investigated the relation of potentially modifiable factors (physical activity level, weight concern, and depressive symptoms) to binge drinking while controlling for the effects of previously established correlates of binge drinking (tobacco and…

Towards a New Generation: A Primary Prevention Plan for New Jersey. A Report.

ERIC Educational Resources Information Center

New Jersey Governor's Juvenile Justice and Delinquency Prevention Advisory Committee, Trenton, NJ.

The New Jersey Juvenile Justice and Delinquency Prevention Advisory Committee and its Prevention Subcommittee have developed an interagency plan to promote primary prevention activities statewide. The plan identifies the initial steps which must be undertaken by major sectors of the community to begin to effectively coordinate activities and…

Altering lipase activity and enantioselectivity in organic media using organo-soluble bases: Implication for rate-limiting proton transfer in acylation step.

PubMed

Chen, Chun-Chi; Chen, Teh-Liang; Tsai, Shau-Wei

2006-06-05

With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis-Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators. Copyright 2006 Wiley Periodicals, Inc.

The Impact of a Community-Based Chronic Disease Prevention Initiative: Evaluation Findings from "Steps to Health King County"

ERIC Educational Resources Information Center

Cheadle, Allen; Bourcier, Emily; Krieger, James; Beery, William; Smyser, Michael; Vinh, Diana V.; Lessler, Dan; Alfonsi, Lorrie

2011-01-01

"Steps to Health King County" ("Steps KC"; Seattle, Washington) was one of 40 community-level initiatives funded in 2003 as part of the "Steps to a HealthierUS" initiative. "Steps KC" goals included reducing the impact of chronic diseases through a comprehensive, coordinated approach and reducing health…

Surface Modified Particles By Multi-Step Michael-Type Addition And Process For The Preparation Thereof

DOEpatents

Cook, Ronald Lee; Elliott, Brian John; Luebben, Silvia DeVito; Myers, Andrew William; Smith, Bryan Matthew

2005-05-03

A new class of surface modified particles and a multi-step Michael-type addition surface modification process for the preparation of the same is provided. The multi-step Michael-type addition surface modification process involves two or more reactions to compatibilize particles with various host systems and/or to provide the particles with particular chemical reactivities. The initial step comprises the attachment of a small organic compound to the surface of the inorganic particle. The subsequent steps attach additional compounds to the previously attached organic compounds through reactive organic linking groups. Specifically, these reactive groups are activated carbon—carbon pi bonds and carbon and non-carbon nucleophiles that react via Michael or Michael-type additions.

The Virtual Physiological Human - a European initiative for in silico human modelling -.

PubMed

Viceconti, Marco; Clapworthy, Gordon; Van Sint Jan, Serge

2008-12-01

The Virtual Physiological Human (VPH) is an initiative, strongly supported by the European Commission (EC), that seeks to develop an integrated model of human physiology at multiple scales from the whole body through the organ, tissue, cell and molecular levels to the genomic level. VPH had its beginnings in 2005 with informal discussions amongst like-minded scientists which led to the STEP project, a Coordination Action funded by the EC that began in early 2006. The STEP project greatly accelerated the progress of the VPH and proved to be a catalyst for wide-ranging discussions within Europe and for outreach activities designed to develop a broad international approach to the huge scientific and technological challenges involved in this area. This paper provides an overview of the VPH and the developments it has engendered in the rapidly expanding worldwide activities associated with the physiome. It then uses one particular project, the Living Human Project, to illustrate the type of advances that are taking place to further the aims of the VPH and similar initiatives worldwide.

The New Hampshire Ten Steps to Successful Breastfeeding Collaborative: A Statewide QI Initiative.

PubMed

Whalen, Bonny L; Kelly, Joyce; Holmes, Alison Volpe

2015-06-01

Despite national recognition for their breastfeeding-friendly practices, many New Hampshire hospitals are still not achieving the Ten Steps to Successful Breastfeeding. To increase achievement of the Ten Steps in New Hampshire's birthing hospitals, facilitate Baby-Friendly Hospital Initiative (BFHI) designation for interested hospitals, and improve rates of in-hospital any and exclusive breastfeeding. After a 2010 needs assessment, we conducted 2 statewide workshops targeting 6 of the Ten Steps found to be most deficient among New Hampshire birthing hospitals. Eighteen of 20 hospitals attended at least 1 workshop, and 6 participated in an intensive collaborative. In 2013, we analyzed interval Ten Step achievement and in-hospital breastfeeding trends. Staff education showed the greatest improvement, increasing step 2 achievement from 1 to 6 hospitals (P=.05). Although the number of hospitals implementing step 6 (breast milk only) and step 9 (no artificial nipples) increased, differences were not statistically significant. Intensive collaborative hospitals achieved an average of 1.5 new steps, whereas non-Baby Friendly hospitals lost 0.7 steps (P=.05). In-hospital breastfeeding rates increased in intensive collaborative hospitals and were significantly higher than those in non-Baby Friendly hospitals by the end of the study (any breastfeeding, 89% vs 73%, P=.03; exclusive breastfeeding, 84% vs 61%, P<.001). A statewide improvement collaborative facilitated increases in Ten Step achievement and in-hospital breastfeeding for hospitals participating in an intensive collaborative. Active work in Ten Step implementation, including staff education, appears to be more effective in increasing in-hospital breastfeeding than does BFHI designation alone. Copyright © 2015 by the American Academy of Pediatrics.

Phase-dependent organization of postural adjustments associated with arm movements while walking.

PubMed

Nashner, L M; Forssberg, H

1986-06-01

This study examines the interactions between anteroposterior postural responses and the control of walking in human subjects. In the experimental paradigm, subjects walked upon a treadmill, gripping a rigid handle with one hand. Postural responses at different phases of stepping were elicited by rapid arm pulls or pushes against the handle. During arm movements, EMG's recorded the activity of representative arm, ankle, and thigh segment muscles. Strain gauges in the handle measured the force of the arm movement. A Selspot II system measured kinematics of the stepping movements. The duration of support and swing phases were marked by heel and toe switches in the soles of the subjects' shoes. In the first experiment, subjects were instructed to pull on the handle at their own pace. In these trials all subjects preferred to initiate pulls near heel strikes. Next, when instructed to pull as rapidly as possible in response to tone stimuli, reaction times were similar for all phases of the step cycle. Leg muscle responses associated with arm pulls and pushes, referred to as "postural activations," were directionally specific and preceded arm muscle activity. The temporal order and spatial distribution of postural activations in the muscles of the support leg were similar when arm pull movements occurred while the subject was standing in place and after heel strike while walking. Activations began in the ankle and radiated proximally to the thigh and then the arm. Activations of swing leg muscles were also directionally specific and involved flexion and forward or backward thrust of the limb. When arm movements were initiated during transitions from support by one leg to the other, patterns of postural activations were altered. Alterations usually occurred 10-20 ms before hell strikes and involved changes in the timing and sometimes the spatial structure of postural activations. Postural activation patterns are similar during in-place standing and during the support phase of locomotion. Walking and posture control appear to be separately organized but interrelated activities. Our results also suggest that the stepping generators, not peripheral feedback time locked to heel strikes, modulate postural activation patterns.

Omega-3 Free Fatty Acids Suppress Macrophage Inflammasome Activation by Inhibiting NF-κB Activation and Enhancing Autophagy

PubMed Central

Williams-Bey, Yolanda; Boularan, Cedric; Vural, Ali; Huang, Ning-Na; Hwang, Il-Young; Shan-Shi, Chong; Kehrl, John H.

2014-01-01

The omega-3 (ω3) fatty acid docosahexaenoic acid (DHA) can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR) 4 (also known as GPR120), a G-protein coupled receptor (GPR) known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity. PMID:24911523

PRELIMINARY CHARACTERIZATION OF FOUR 2-CHLOROBENZOATE-DEGRADING ANAEROBIC BACTERIAL CONSORTIA

EPA Science Inventory

Dechlorination was the initial step of 2CB biodegradation in four 2-chlorobenzoate-degrading methanogenic consortia. Selected characteristics of orthoreductive dehalogenation were examined in consortia developed from the highest actively dechlorinating dilutions of the original 2...

Managing Low-Back Pain: Steps To Optimize Function and Hasten Return to Activity.

ERIC Educational Resources Information Center

Drezner, Jonathan A.; Herring, Stanley A.

2001-01-01

Low-back pain (LBP) in active people is common and recurrent. This paper describes: the natural history and clinical course of LBP; anatomy and biomechanics of LBP; what causes pain; diagnosis; initial treatment (e.g., pain and inflammation control, bed rest, and exercises); rehabilitation (e.g., lumbar stabilization exercises, conditioning, and…

Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide*

PubMed Central

Sassa, Akira; Çağlayan, Melike; Dyrkheeva, Nadezhda S.; Beard, William A.; Wilson, Samuel H.

2014-01-01

Cytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA glycosylase (TDG) initiated base excision repair (BER). A further consideration is that guanine in the CpG dinucleotide may become oxidized to 7,8-dihydro-8-oxoguanine (8-oxoG), and this could affect the demethylation process involving TDG-initiated BER. However, little is known about the enzymology of BER of altered in-tandem CpG dinucleotides; e.g. Tp8-oxoG. Here, we investigated interactions between this altered dinucleotide and purified BER enzymes, the DNA glycosylases TDG and 8-oxoG DNA glycosylase 1 (OGG1), apurinic/apyrimidinic (AP) endonuclease 1, DNA polymerase β, and DNA ligases. The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduced. Specifically, TDG and DNA ligase activities are reduced by a 3′-flanking 8-oxoG. In contrast, the OGG1-initiated BER pathway is blocked due to the 5′-flanking T:G mispair; this reduces OGG1, AP endonuclease 1, and DNA polymerase β activities. Furthermore, in TDG-initiated BER, TDG remains bound to its product AP site blocking OGG1 access to the adjacent 8-oxoG. These results reveal BER enzyme specificities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide. PMID:24695738

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

PubMed Central

2014-01-01

Background During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Methods Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. Results The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134–353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030). Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). Conclusions COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. PMID:24885188

Marketing physical activity: lessons learned from a statewide media campaign.

PubMed

Peterson, Michael; Abraham, Avron; Waterfield, Allan

2005-10-01

Steps taken to create, implement, and initially assess a statewide physical activity social marketing campaign targeted to 18-to 30-year-olds are presented. Included is a summary demonstration of the application of the associative group analysis in formative market research and message development. Initial postcampaign questionnaire (n = 363) results indicated that 39.1% of respondents had seen the television ad, of which 31.2% indicated they intended to be more active, and 62.5% of respondents had been exposed to either the television or outdoor media ads. Lessons learned through the social marketing process including media channel effectiveness, message development and assessment, and marketing firm relationships are provided.

A National Cohort Study of U.S. Medical School Students Who Initially Failed Step 1 of the United States Medical Licensing Examination

PubMed Central

Andriole, Dorothy A.; Jeffe, Donna B.

2012-01-01

Purpose To describe educational outcomes for a national cohort of U.S. medical students who initially failed Step 1 of the United States Medical Licensing Examination Method The authors analyzed de-identified, individualized records for the 1993–2000 cohort of U.S. medical school matriculants who both initially failed Step l and were no longer in medical school as of March 2, 2009, using multivariable logistic regression to identify factors associated with attempting, and initially passing, Step 2 Clinical Knowledge (CK). Results Of 6,594 students who failed Step l, 5,985 (90.8%) took Step 2CK. Women and Asian/Pacific Islander students were more likely to attempt Step 2CK; more recent matriculants and students with lower failing Step 1 scores were less likely. Of the 5,985 students who attempted Step 2CK, 4,168 (69.6%) initially passed. Women, students with higher Medical College Admission Test scores, and more recent matriculants were more likely to pass Step 2CK; Asian/Pacific Islander students, underrepresented minority students, older students, and students with lower failing Step 1 scores were less likely. Ninety percent of students in the study sample (5,952/6,594) ultimately graduated from medical school, including 99.5% (4,148/4,168) of those who initially passed, 96.7% (1,757/1,817) of those who initially failed, and 7.7% (47/609) of those who never attempted Step 2CK. Conclusions The authors identified variables associated with educational outcomes among students who failed Step l. These findings can inform medical schools’ efforts to develop tailored interventions to maximize the likelihood that students will take Step 2CK and pass it on the first attempt. PMID:22361789

Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

PubMed Central

Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

2013-01-01

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612

Activation Energy of the Low-pH-Induced Lamellar to Bicontinuous Cubic Phase Transition in Dioleoylphosphatidylserine/Monoolein.

PubMed

Oka, Toshihiko; Saiki, Takahiro; Alam, Jahangir Md; Yamazaki, Masahito

2016-02-09

Electrostatic interaction is an important factor for phase transitions between lamellar liquid-crystalline (Lα) and inverse bicontinuous cubic (QII) phases. We investigated the effect of temperature on the low-pH-induced Lα to double-diamond cubic (QII(D)) phase transition in dioleoylphosphatidylserine (DOPS)/monoolein (MO) using time-resolved small-angle X-ray scattering with a stopped-flow apparatus. Under all conditions of temperature and pH, the Lα phase was directly transformed into an intermediate inverse hexagonal (HII) phase, and subsequently the HII phase slowly converted to the QII(D) phase. We obtained the rate constants of the initial step (i.e., the Lα to HII phase transition) and of the second step (i.e., the HII to QII(D) phase transition) using the non-negative matrix factorization method. The rate constant of the initial step increased with temperature. By analyzing this result, we obtained the values of its apparent activation energy, Ea (Lα → HII), which did not change with temperature but increased with an increase in pH. In contrast, the rate constant of the second step decreased with temperature at pH 2.6, although it increased with temperature at pH 2.7 and 2.8. These results indicate that the value of Ea (HII → QII(D)) at pH 2.6 increased with temperature, but the values of Ea (HII → QII(D)) at pH 2.7 and 2.8 were constant with temperature. The values of Ea (HII → QII(D)) were smaller than those of Ea (Lα → HII) at the same pH. We analyzed these results using a modified quantitative theory on the activation energy of phase transitions of lipid membranes proposed initially by Squires et al. (Squires, A. M.; Conn, C. E.; Seddon, J. M.; Templer, R. H. Soft Matter 2009, 5, 4773). On the basis of these results, we discuss the mechanism of this phase transition.

Apparatus and method for polarizing polarizable nuclear species

DOEpatents

Hersman, F. William; Leuschner, Mark; Carberry, Jeannette

2005-09-27

The present invention is a polarizing process involving a number of steps. The first step requires moving a flowing mixture of gas, the gas at least containing a polarizable nuclear species and vapor of at least one alkali metal, with a transport velocity that is not negligible when compared with the natural velocity of diffusive transport. The second step is propagating laser light in a direction, preferably at least partially through a polarizing cell. The next step is directing the flowing gas along a direction generally opposite to the direction of laser light propagating. The next step is containing the flowing gas mixture in the polarizing cell. The final step is immersing the polarizing cell in a magnetic field. These steps can be initiated in any order, although the flowing gas, the propagating laser and the magnetic field immersion must be concurrently active for polarization to occur.

Highlights from AQMEII Phase 2 & Next Steps

EPA Science Inventory

We present highlights of the results obtained in the second phase of the Air Quality Model Evaluation International Initiative (AQMEII) that was completed in May 2014. Activities in this phase were focused on the application and evaluation of coupled meteorology-chemistry models ...

Anisotropy in Ostwald ripening and step-terraced surface formation on GaAs(0 0 1): Experiment and Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Kazantsev, D. M.; Akhundov, I. O.; Shwartz, N. L.; Alperovich, V. L.; Latyshev, A. V.

2015-12-01

Ostwald ripening and step-terraced morphology formation on the GaAs(0 0 1) surface during annealing in equilibrium conditions are investigated experimentally and by Monte Carlo simulation. Fourier and autocorrelation analyses are used to reveal surface relief anisotropy and provide information about islands and pits shape and their size distribution. Two origins of surface anisotropy are revealed. At the initial stage of surface smoothing, crystallographic anisotropy is observed, which is caused presumably by the anisotropy of surface diffusion at GaAs(0 0 1). A difference of diffusion activation energies along [1 1 0] and [1 1 bar 0] axes of the (0 0 1) face is estimated as ΔEd ≈ 0.1 eV from the comparison of experimental results and simulation. At later stages of surface smoothing the anisotropy of the surface relief is determined by the vicinal steps direction. At the initial stage of step-terraced morphology formation the kinetics of monatomic islands and pits growth agrees with the Ostwald ripening theory. At the final stage the size of islands and pits decreases due to their incorporation into the forming vicinal steps.

Errors in Postural Preparation Lead to Increased Choice Reaction Times for Step Initiation in Older Adults

PubMed Central

Nutt, John G.; Horak, Fay B.

2011-01-01

Background. This study asked whether older adults were more likely than younger adults to err in the initial direction of their anticipatory postural adjustment (APA) prior to a step (indicating a motor program error), whether initial motor program errors accounted for reaction time differences for step initiation, and whether initial motor program errors were linked to inhibitory failure. Methods. In a stepping task with choice reaction time and simple reaction time conditions, we measured forces under the feet to quantify APA onset and step latency and we used body kinematics to quantify forward movement of center of mass and length of first step. Results. Trials with APA errors were almost three times as common for older adults as for younger adults, and they were nine times more likely in choice reaction time trials than in simple reaction time trials. In trials with APA errors, step latency was delayed, correlation between APA onset and step latency was diminished, and forward motion of the center of mass prior to the step was increased. Participants with more APA errors tended to have worse Stroop interference scores, regardless of age. Conclusions. The results support the hypothesis that findings of slow choice reaction time step initiation in older adults are attributable to inclusion of trials with incorrect initial motor preparation and that these errors are caused by deficits in response inhibition. By extension, the results also suggest that mixing of trials with correct and incorrect initial motor preparation might explain apparent choice reaction time slowing with age in upper limb tasks. PMID:21498431

Trunk Exercises Improve Gait Symmetry in Parkinson Disease: A Blind Phase II Randomized Controlled Trial.

PubMed

Hubble, Ryan P; Naughton, Geraldine; Silburn, Peter A; Cole, Michael H

2018-03-01

Deficits in step-to-step symmetry and trunk muscle activations have been linked to falls in Parkinson disease. Given such symptoms are poorly managed with anti-parkinsonian medications, alternate therapies are needed. This blind phase II randomized controlled trial sought to establish whether exercise can improve step-to-step symmetry in Parkinson disease. Twenty-four Parkinson disease patients with a falls history completed baseline assessments of symptom severity, balance confidence, mobility, and quality of life. Step-to-step symmetry was assessed by deriving harmonic ratios from three-dimensional accelerations collected for the head and trunk. Patients were randomly assigned to either 12 wks of exercise and falls prevention education or falls prevention education only. Both groups repeated the baseline tests 12 and 24 wks after the initial assessment. The Australian and New Zealand Clinical Trials Registry number is ACTRN12613001175763. At 12 wks, the exercise group had statistically significant and clinically relevant improvements in anterior-posterior step-to-step trunk symmetry. In contrast, the education group recorded statistically significant and clinically meaningful reductions in medial-lateral and vertical step-to-step trunk symmetry at 12 wks. Given that step-to-step symmetry improved for the exercise group and declined for the education group after intervention, active interventions seem more suited to increasing independence and quality of life for people with Parkinson disease. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to do the following: (1) Describe the effect deficits in trunk muscle function have on gait in individuals with Parkinson disease; (2) Identify the benefits of targeted trunk exercises on step-to-step symmetry; and (3) Discuss the benefits of improving step-to-step symmetry in individuals with Parkinson disease. Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The initial step in the archaeal aspartate biosynthetic pathway catalyzed by a monofunctional aspartokinase

PubMed Central

Faehnle, Christopher R.; Liu, Xuying; Pavlovsky, Alexander; Viola, Ronald E.

2006-01-01

The activation of the β-carboxyl group of aspartate catalyzed by aspartokinase is the commitment step to amino-acid biosynthesis in the aspartate pathway. The first structure of a microbial aspartokinase, that from Methanococcus jannaschii, has been determined in the presence of the amino-acid substrate l-­aspartic acid and the nucleotide product MgADP. The enzyme assembles into a dimer of dimers, with the interfaces mediated by both the N- and C-terminal domains. The active-site functional groups responsible for substrate binding and specificity have been identified and roles have been proposed for putative catalytic functional groups. PMID:17012784

Investigation of infrared radiation in rubidium vapor upon two-photon and step-by-step excitations of the initial level

NASA Astrophysics Data System (ADS)

Bimagambetov, T. S.

2011-12-01

Stimulated infrared (IR) 5.231-μm line radiation is obtained upon two-photon and step-by-step excitations of the initial level. Dependences of the line power on the concentration of atoms and laser frequency are investigated. The mechanism of initial level occupation is explained.

A dynamic dual role of IL-2 signaling in the two-step differentiation process of adaptive regulatory T cells.

PubMed

Guo, Zhiyong; Khattar, Mithun; Schroder, Paul M; Miyahara, Yoshihiro; Wang, Guohua; He, Xiaoshung; Chen, Wenhao; Stepkowski, Stanislaw M

2013-04-01

The molecular mechanism of the extrathymic generation of adaptive, or inducible, CD4(+)Foxp3(+) regulatory T cells (iTregs) remains incompletely defined. We show that exposure of splenic CD4(+)CD25(+)Foxp3(-) cells to IL-2, but not other common γ-chain cytokines, resulted in Stat5 phosphorylation and induced Foxp3 expression in ∼10% of the cells. Thus, IL-2/Stat5 signaling may be critical for Foxp3 induction in peripheral CD4(+)CD25(+)Foxp3(-) iTreg precursors. In this study, to further define the role of IL-2 in the formation of iTreg precursors as well as their subsequent Foxp3 expression, we designed a two-step iTreg differentiation model. During the initial "conditioning" step, CD4(+)CD25(-)Foxp3(-) naive T cells were activated by TCR stimulation. Inhibition of IL-2 signaling via Jak3-Stat5 was required during this step to generate CD4(+)CD25(+)Foxp3(-) cells containing iTreg precursors. During the subsequent Foxp3-induction step driven by cytokines, IL-2 was the most potent cytokine to induce Foxp3 expression in these iTreg precursors. This two-step method generated a large number of iTregs with relatively stable expression of Foxp3, which were able to prevent CD4(+)CD45RB(high) cell-mediated colitis in Rag1(-/-) mice. In consideration of this information, whereas initial inhibition of IL-2 signaling upon T cell priming generates iTreg precursors, subsequent activation of IL-2 signaling in these precursors induces the expression of Foxp3. These findings advance the understanding of iTreg differentiation and may facilitate the therapeutic use of iTregs in immune disorders.

Healthy Eating and Physical Activity in Schools in Europe: A Toolkit for Policy Development and Its Implementation

ERIC Educational Resources Information Center

Simovska, Venka; Dadaczynski, Kevin; Woynarowska, Barbara

2012-01-01

Purpose: The purpose of this paper is to introduce the HEPS project ("H"ealthy "E"ating and "P"hysical Activity in "S"chools) and discuss initial steps of the project implementation within EU countries. On the basis of the Health Promoting School approach as a conceptual foundation for the project, HEPS…

The development of a new three-step protocol to determine the efficacy of disinfectant wipes on surfaces contaminated with Staphylococcus aureus.

PubMed

Williams, G J; Denyer, S P; Hosein, I K; Hill, D W; Maillard, J-Y

2007-12-01

We developed a three-step protocol to quantify the efficacy of disinfectant wipes, their ability to remove and prevent microbial transfer from surfaces and their overall antimicrobial activity. Meticillin-resistant (MRSA) or -susceptible (MSSA) Staphylococcus aureus (6-7 log(10)cfu) were inoculated onto stainless steel discs with or without organic load and dried. Grapefruit extract-containing test wipes and unmedicated control wipes were used. In step 1, wipes were mechanically rotated against surfaces for 10s at 60rpm, exerting a weight of 100+/-5g. Bacterial removal was assessed by transferring the steel discs to neutraliser, resuspending and counting remaining bacteria. In step 2, bacterial transfer from wipes was assessed by eight consecutive mechanical adpression transfers to agar/neutraliser plates. Step 3 was the measurement of antimicrobial activity by direct inoculation of the wipes for 10s followed by neutralisation and enumeration. Test wipes achieved a significantly higher bacterial cell removal than control wipes on all surfaces (P<0.05). The low bactericidal activity of the wipes (<1 log(10) reduction when directly inoculated) and the subsequent survival of bacteria on the wipes, however, led to repeated microbial transfer when initially high contamination levels were present. There were no differences between MRSA and MSSA in removal, transfer or antimicrobial activity. The three-step method is a useful tool for developing future guidelines to assess the ability of wipes to disinfect surfaces.

Postural adjustment errors during lateral step initiation in older and younger adults

PubMed Central

Sparto, Patrick J.; Fuhrman, Susan I.; Redfern, Mark S.; Perera, Subashan; Jennings, J. Richard; Furman, Joseph M.

2016-01-01

The purpose was to examine age differences and varying levels of step response inhibition on the performance of a voluntary lateral step initiation task. Seventy older adults (70 – 94 y) and twenty younger adults (21 – 58 y) performed visually-cued step initiation conditions based on direction and spatial location of arrows, ranging from a simple choice reaction time task to a perceptual inhibition task that included incongruous cues about which direction to step (e.g. a left pointing arrow appearing on the right side of a monitor). Evidence of postural adjustment errors and step latencies were recorded from vertical ground reaction forces exerted by the stepping leg. Compared with younger adults, older adults demonstrated greater variability in step behavior, generated more postural adjustment errors during conditions requiring inhibition, and had greater step initiation latencies that increased more than younger adults as the inhibition requirements of the condition became greater. Step task performance was related to clinical balance test performance more than executive function task performance. PMID:25595953

Postural adjustment errors during lateral step initiation in older and younger adults

PubMed Central

Sparto, Patrick J.; Fuhrman, Susan I.; Redfern, Mark S.; Perera, Subashan; Jennings, J. Richard; Furman, Joseph M.

2014-01-01

The purpose was to examine age differences and varying levels of step response inhibition on the performance of a voluntary lateral step initiation task. Seventy older adults (70 – 94 y) and twenty younger adults (21 – 58 y) performed visually-cued step initiation conditions based on direction and spatial location of arrows, ranging from a simple choice reaction time task to a perceptual inhibition task that included incongruous cues about which direction to step (e.g. a left pointing arrow appearing on the right side of a monitor). Evidence of postural adjustment errors and step latencies were recorded from vertical ground reaction forces exerted by the stepping leg. Compared with younger adults, older adults demonstrated greater variability in step behavior, generated more postural adjustment errors during conditions requiring inhibition, and had greater step initiation latencies that increased more than younger adults as the inhibition requirements of the condition became greater. Step task performance was related to clinical balance test performance more than executive function task performance. PMID:25183162

Preclinic group education sessions reduce waiting times and costs at public pain medicine units.

PubMed

Davies, Stephanie; Quintner, John; Parsons, Richard; Parkitny, Luke; Knight, Paul; Forrester, Elizabeth; Roberts, Mary; Graham, Carl; Visser, Eric; Antill, Tracy; Packer, Tanya; Schug, Stephan A

2011-01-01

To assess the effects of preclinic group education sessions and system redesign on tertiary pain medicine units and patient outcomes. Prospective cohort study. Two public hospital multidisciplinary pain medicine units. People with persistent pain. A system redesign from a "traditional" model (initial individual medical appointments) to a model that delivers group education sessions prior to individual appointments. Based on Patient Triage Questionnaires patients were scheduled to attend Self-Training Educative Pain Sessions (STEPS), a two day eight hour group education program, followed by optional patient-initiated clinic appointments. Number of patients completing STEPS who subsequently requested individual outpatient clinic appointment(s); wait-times; unit cost per new patient referred; recurrent health care utilization; patient satisfaction; Global Perceived Impression of Change (GPIC); and utilized pain management strategies. Following STEPS 48% of attendees requested individual outpatient appointments. Wait times reduced from 105.6 to 16.1 weeks at one pain unit and 37.3 to 15.2 weeks at the second. Unit cost per new patient appointed reduced from $1,805 Australian Dollars (AUD) to AUD$541 (for STEPS). At 3 months, patients scored their satisfaction with "the treatment received for their pain" more positively than at baseline (change score=0.88; P=0.0003), GPIC improved (change score=0.46; P<0.0001) and mean number of active strategies utilized increased by 4.12 per patient (P=0.0004). The introduction of STEPS was associated with reduced wait-times and costs at public pain medicine units and increased both the use of active pain management strategies and patient satisfaction. Wiley Periodicals, Inc.

Conversion of Cn-Unsaturated into Cn-2-Saturated LCFA Can Occur Uncoupled from Methanogenesis in Anaerobic Bioreactors.

PubMed

Cavaleiro, Ana J; Pereira, Maria Alcina; Guedes, Ana P; Stams, Alfons J M; Alves, M Madalena; Sousa, Diana Z

2016-03-15

Fat, oils, and grease present in complex wastewater can be readily converted to methane, but the energy potential of these compounds is not always recyclable, due to incomplete degradation of long chain fatty acids (LCFA) released during lipids hydrolysis. Oleate (C18:1) is generally the dominant LCFA in lipid-containing wastewater, and its conversion in anaerobic bioreactors results in palmitate (C16:0) accumulation. The reason why oleate is continuously converted to palmitate without further degradation via β-oxidation is still unknown. In this work, the influence of methanogenic activity in the initial conversion steps of unsaturated LCFA was studied in 10 bioreactors continuously operated with saturated or unsaturated C16- and C18-LCFA, in the presence or absence of the methanogenic inhibitor bromoethanesulfonate (BrES). Saturated Cn-2-LCFA accumulated both in the presence and absence of BrES during the degradation of unsaturated Cn-LCFA, and represented more than 50% of total LCFA. In the presence of BrES further conversion of saturated intermediates did not proceed, not even when prolonged batch incubation was applied. As the initial steps of unsaturated LCFA degradation proceed uncoupled from methanogenesis, accumulation of saturated LCFA can be expected. Analysis of the active microbial communities suggests a role for facultative anaerobic bacteria in the initial steps of unsaturated LCFA biodegradation. Understanding this role is now imperative to optimize methane production from LCFA.

Factors associated with high levels of physical activity among adults with intellectual disability.

PubMed

Temple, Viviene A

2009-03-01

The aim was to identify factors associated with physical activity participation among active (i.e. more than or equal to 10,000 steps per day) individuals with intellectual disability. Staff at day program and supported employment organizations were asked to identify individuals they believed were physically active. To verify participants were active, 7-day pedometer data were collected. Using these data, 13 participants met the inclusion criterion of 10,000 steps per day from 37 individuals identified by staff. Participants (n=13) ranged in age from 18 to 46 years (mean=34, SD= 8) and seven were male. In-depth semistructured interviews were conducted to explore the environmental and social supports for these high levels of physical activity. Three major themes were identified from content and thematic analyses. Key individuals and organizations were important in fostering initial interests and the development of skills. Coaches, staff and parents were important in 'showing them how.' For example, how to vacuum or stack produce, how to bowl, how to use weight training equipment or helping to plan a safe walking route. Motivation for initial and ongoing participation was associated with friendship and social connection. Practical support was needed for continued participation. In particular, transportation and affordable activities were very important. Fostering practical skills, supporting the social aspects of physical activity and keeping activities low cost are important enabling and reinforcing factors for physical activity among active persons with intellectual disability.

Two-step membrane binding by the bacterial SRP receptor enable efficient and accurate Co-translational protein targeting.

PubMed

Hwang Fu, Yu-Hsien; Huang, William Y C; Shen, Kuang; Groves, Jay T; Miller, Thomas; Shan, Shu-Ou

2017-07-28

The signal recognition particle (SRP) delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum, or the bacterial plasma membrane. The precise mechanism by which the bacterial SRP receptor, FtsY, interacts with and is regulated at the target membrane remain unclear. Here, quantitative analysis of FtsY-lipid interactions at single-molecule resolution revealed a two-step mechanism in which FtsY initially contacts membrane via a Dynamic mode, followed by an SRP-induced conformational transition to a Stable mode that activates FtsY for downstream steps. Importantly, mutational analyses revealed extensive auto-inhibitory mechanisms that prevent free FtsY from engaging membrane in the Stable mode; an engineered FtsY pre-organized into the Stable mode led to indiscriminate targeting in vitro and disrupted FtsY function in vivo. Our results show that the two-step lipid-binding mechanism uncouples the membrane association of FtsY from its conformational activation, thus optimizing the balance between the efficiency and fidelity of co-translational protein targeting.

Development of an mHealth Intervention (iSTEP) to Promote Physical Activity among People Living with HIV.

PubMed

Montoya, Jessica L; Wing, David; Knight, Adam; Moore, David J; Henry, Brook L

2015-01-01

A randomized controlled trial is being conducted in the United States to test the efficacy of a personalized interactive mobile health intervention (iSTEP) designed to increase physical activity (PA) and improve neurocognitive functioning among HIV-positive persons. This article describes an initial qualitative study performed to develop iSTEP for the HIV-positive population, including assessment of PA barriers and facilitators. Two focus groups, with 9 and 12 unique HIV-positive individuals, respectively, were administered to evaluate barriers limiting PA and potential iSTEP content created to encourage greater PA. Group discussions revealed prominent PA barriers, including HIV symptoms (neuropathy, lipoatrophy), antiretroviral medication effects, and fatigue; significant PA facilitators included self-monitoring and family support. Participants provided feedback on strategies to increase PA and expressed positive support for a mobile intervention adapted to personal priorities. These findings will assist the development of novel PA interventions focused on treating the epidemic of HIV-associated neurocognitive disorders. © The Author(s) 2015.

Step-to-step spatiotemporal variables and ground reaction forces of intra-individual fastest sprinting in a single session.

PubMed

Nagahara, Ryu; Mizutani, Mirai; Matsuo, Akifumi; Kanehisa, Hiroaki; Fukunaga, Tetsuo

2018-06-01

We aimed to investigate the step-to-step spatiotemporal variables and ground reaction forces during the acceleration phase for characterising intra-individual fastest sprinting within a single session. Step-to-step spatiotemporal variables and ground reaction forces produced by 15 male athletes were measured over a 50-m distance during repeated (three to five) 60-m sprints using a long force platform system. Differences in measured variables between the fastest and slowest trials were examined at each step until the 22nd step using a magnitude-based inferences approach. There were possibly-most likely higher running speed and step frequency (2nd to 22nd steps) and shorter support time (all steps) in the fastest trial than in the slowest trial. Moreover, for the fastest trial there were likely-very likely greater mean propulsive force during the initial four steps and possibly-very likely larger mean net anterior-posterior force until the 17th step. The current results demonstrate that better sprinting performance within a single session is probably achieved by 1) a high step frequency (except the initial step) with short support time at all steps, 2) exerting a greater mean propulsive force during initial acceleration, and 3) producing a greater mean net anterior-posterior force during initial and middle acceleration.

Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol.

PubMed

Cencic, Regina; Carrier, Marilyn; Galicia-Vázquez, Gabriela; Bordeleau, Marie-Eve; Sukarieh, Rami; Bourdeau, Annie; Brem, Brigitte; Teodoro, Jose G; Greger, Harald; Tremblay, Michel L; Porco, John A; Pelletier, Jerry

2009-01-01

Flavaglines are a family of natural products from the genus Aglaia that exhibit anti-cancer activity in vitro and in vivo and inhibit translation initiation. They have been shown to modulate the activity of eIF4A, the DEAD-box RNA helicase subunit of the eukaryotic initiation factor (eIF) 4F complex, a complex that stimulates ribosome recruitment during translation initiation. One flavagline, silvestrol, is capable of modulating chemosensitivity in a mechanism-based mouse model. Among a number of flavagline family members tested herein, we find that silvestrol is the more potent translation inhibitor among these. We find that silvestrol impairs the ribosome recruitment step of translation initiation by affecting the composition of the eukaryotic initiation factor (eIF) 4F complex. We show that silvestrol exhibits significant anticancer activity in human breast and prostate cancer xenograft models, and that this is associated with increased apoptosis, decreased proliferation, and inhibition of angiogenesis. We demonstrate that targeting translation by silvestrol results in preferential inhibition of weakly initiating mRNAs. Our results indicate that silvestrol is a potent anti-cancer compound in vivo that exerts its activity by affecting survival pathways as well as angiogenesis. We propose that silvestrol mediates its effects by preferentially inhibiting translation of malignancy-related mRNAs. Silvestrol appears to be well tolerated in animals.

Neural mechanisms of single corrective steps evoked in the standing rabbit

PubMed Central

Hsu, L.-J.; Zelenin, P. V.; Lyalka, V. F.; Vemula, M. G.; Orlovsky, G. N.; Deliagina, T. G.

2017-01-01

Single steps in different directions are often used for postural corrections. However, our knowledge about the neural mechanisms underlying their generation is scarce. This study was aimed to characterize the corrective steps generated in response to disturbances of the basic body configuration caused by forward, backward or outward displacement of the hindlimb, as well as to reveal location in the CNS of the corrective step generating mechanisms. Video recording of the motor response to translation of the supporting surface under the hindlimb along with contact forces and activity of back and limb muscles was performed in freely standing intact and in fixed postmammillary rabbits. In intact rabbits, displacement of the hindlimb in any direction caused a lateral trunk movement towards the contralateral hindlimb, and then a corrective step in the direction opposite to the initial displacement. The time difference between onsets of these two events varied considerably. The EMG pattern in the supporting hindlimb was similar for all directions of corrective steps. It caused the increase in the limb stiffness. EMG pattern in the stepping limb differed in steps with different directions. In postmammillary rabbits the corrective stepping movements, as well as EMG patterns in both stepping and standing hindlimbs were similar to those observed in intact rabbits. This study demonstrates that the corrective trunk and limb movements are generated by separate mechanisms activated by sensory signals from the deviated limb. The neuronal networks generating postural corrective steps reside in the brainstem, cerebellum, and spinal cord. PMID:28215990

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

PubMed

Hofstoetter, Ursula S; Krenn, Matthias; Danner, Simon M; Hofer, Christian; Kern, Helmut; McKay, William B; Mayr, Winfried; Minassian, Karen

2015-10-01

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

UV-induced photocatalytic degradation of aqueous acetaminophen: the role of adsorption and reaction kinetics.

PubMed

Basha, Shaik; Keane, David; Nolan, Kieran; Oelgemöller, Michael; Lawler, Jenny; Tobin, John M; Morrissey, Anne

2015-02-01

Nanostructured titania supported on activated carbon (AC), termed as integrated photocatalytic adsorbents (IPCAs), were prepared by ultrasonication and investigated for the photocatalytic degradation of acetaminophen (AMP), a common analgesic and antipyretic drug. The IPCAs showed high affinity towards AMP (in dark adsorption studies), with the amount adsorbed proportional to the TiO2 content; the highest adsorption was at 10 wt% TiO2. Equilibrium isotherm studies showed that the adsorption followed the Langmuir model, indicating the dependence of the reaction on an initial adsorption step, with maximum adsorption capacity of 28.4 mg/g for 10 % TiO2 IPCA. The effects of initial pH, catalyst amount and initial AMP concentration on the photocatalytic degradation rates were studied. Generally, the AMP photodegradation activity of the IPCAs was better than that of bare TiO2. Kinetic studies on the photocatalytic degradation of AMP under UV suggest that the degradation followed Langmuir-Hinshelwood (L-H) kinetics, with an adsorption rate constant (K) that was considerably higher than the photocatalytic rate constant (k r), indicating that the photocatalysis of AMP is the rate-determining step during the adsorption/photocatalysis process.

Flow diverter value and flow diversion method

NASA Technical Reports Server (NTRS)

Arline, S. B.; Carlson, R. L. (Inventor)

1964-01-01

A flow diverter valve applicable to any fluid flow system requiring rapid bleed or bypass is disclosed. Examples of application of the flow diverter valve to a liquid rocket and a turbojet aircraft engine are given. Features of the valve include: (1) an independent fluid source is used to activate the flow diverter valve toward its closed position during its initial stage of travel; (2) the flow diverter port area and size is unlimited and the valve travel is unlimited; and (3) the valve housing is fabricated such that the valve can be a one step valve, a two step valve, or include as many steps as are found desirable.

Antioncogenes.

ERIC Educational Resources Information Center

Oppenheimer, Steven B.

1988-01-01

Discusses one mechanism proposed for the two-step initiation/promotion scenario of the development of cancer called oncogenes and a possible alternate mechanism that may prevent tumors from developing. Uses the example of retinoblastoma to illustrate the mechanisms. States that these mechanisms may not be caused by the activation of oncogenes. (CW)

Performance monitoring and response conflict resolution associated with choice stepping reaction tasks.

PubMed

Watanabe, Tatsunori; Tsutou, Kotaro; Saito, Kotaro; Ishida, Kazuto; Tanabe, Shigeo; Nojima, Ippei

2016-11-01

Choice reaction requires response conflict resolution, and the resolution processes that occur during a choice stepping reaction task undertaken in a standing position, which requires maintenance of balance, may be different to those processes occurring during a choice reaction task performed in a seated position. The study purpose was to investigate the resolution processes during a choice stepping reaction task at the cortical level using electroencephalography and compare the results with a control task involving ankle dorsiflexion responses. Twelve young adults either stepped forward or dorsiflexed the ankle in response to a visual imperative stimulus presented on a computer screen. We used the Simon task and examined the error-related negativity (ERN) that follows an incorrect response and the correct-response negativity (CRN) that follows a correct response. Error was defined as an incorrect initial weight transfer for the stepping task and as an incorrect initial tibialis anterior activation for the control task. Results revealed that ERN and CRN amplitudes were similar in size for the stepping task, whereas the amplitude of ERN was larger than that of CRN for the control task. The ERN amplitude was also larger in the stepping task than the control task. These observations suggest that a choice stepping reaction task involves a strategy emphasizing post-response conflict and general performance monitoring of actual and required responses and also requires greater cognitive load than a choice dorsiflexion reaction. The response conflict resolution processes appear to be different for stepping tasks and reaction tasks performed in a seated position.

Spring-Loaded Model Revisited: Paramyxovirus Fusion Requires Engagement of a Receptor Binding Protein beyond Initial Triggering of the Fusion Protein▿

PubMed Central

Porotto, Matteo; DeVito, Ilaria; Palmer, Samantha G.; Jurgens, Eric M.; Yee, Jia L.; Yokoyama, Christine C.; Pessi, Antonello; Moscona, Anne

2011-01-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry. PMID:21976650

Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein.

PubMed

Porotto, Matteo; Devito, Ilaria; Palmer, Samantha G; Jurgens, Eric M; Yee, Jia L; Yokoyama, Christine C; Pessi, Antonello; Moscona, Anne

2011-12-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry.

Anticipatory Postural Adjustment During Self-Initiated, Cued, and Compensatory Stepping in Healthy Older Adults and Patients With Parkinson Disease.

PubMed

Schlenstedt, Christian; Mancini, Martina; Horak, Fay; Peterson, Daniel

2017-07-01

To characterize anticipatory postural adjustments (APAs) across a variety of step initiation tasks in people with Parkinson disease (PD) and healthy subjects. Cross-sectional study. Step initiation was analyzed during self-initiated gait, perceptual cued gait, and compensatory forward stepping after platform perturbation. People with PD were assessed on and off levodopa. University research laboratory. People (N=31) with PD (n=19) and healthy aged-matched subjects (n=12). Not applicable. Mediolateral (ML) size of APAs (calculated from center of pressure recordings), step kinematics, and body alignment. With respect to self-initiated gait, the ML size of APAs was significantly larger during the cued condition and significantly smaller during the compensatory condition (P<.001). Healthy subjects and patients with PD did not differ in body alignment during the stance phase prior to stepping. No significant group effect was found for ML size of APAs between healthy subjects and patients with PD. However, the reduction in APA size from cued to compensatory stepping was significantly less pronounced in PD off medication compared with healthy subjects, as indicated by a significant group by condition interaction effect (P<.01). No significant differences were found comparing patients with PD on and off medications. Specific stepping conditions had a significant effect on the preparation and execution of step initiation. Therefore, APA size should be interpreted with respect to the specific stepping condition. Across-task changes in people with PD were less pronounced compared with healthy subjects. Antiparkinsonian medication did not significantly improve step initiation in this mildly affected PD cohort. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Activation Thermodynamics and H/D Kinetic Isotope Effect of the Hox to HredH+ Transition in [FeFe] Hydrogenase.

PubMed

Ratzloff, Michael W; Wilker, Molly B; Mulder, David W; Lubner, Carolyn E; Hamby, Hayden; Brown, Katherine A; Dukovic, Gordana; King, Paul W

2017-09-20

Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe. The H ox →H red H + reduction step measured by Fourier-transform infrared spectroscopy showed an enthalpy of activation of 19 kJ mol -1 and a ∼2.5-fold kinetic isotope effect. Overall, these results support electron injection from CdSe into CaI involving F-clusters, and that the H ox →H red H + step of catalytic proton reduction in CaI proceeds by a proton-dependent process.

A New Route for High-Purity Organic Materials: High-Pressure-Ramp-Induced Ultrafast Polymerization of 2-(Hydroxyethyl)Methacrylate

NASA Astrophysics Data System (ADS)

Evlyukhin, E.; Museur, L.; Traore, M.; Perruchot, C.; Zerr, A.; Kanaev, A.

2015-12-01

The synthesis of highly biocompatible polymers is important for modern biotechnologies and medicine. Here, we report a unique process based on a two-step high-pressure ramp (HPR) for the ultrafast and efficient bulk polymerization of 2-(hydroxyethyl)methacrylate (HEMA) at room temperature without photo- and thermal activation or addition of initiator. The HEMA monomers are first activated during the compression step but their reactivity is hindered by the dense glass-like environment. The rapid polymerization occurs in only the second step upon decompression to the liquid state. The conversion yield was found to exceed 90% in the recovered samples. The gel permeation chromatography evidences the overriding role of HEMA2•• biradicals in the polymerization mechanism. The HPR process extends the application field of HP-induced polymerization, beyond the family of crystallized monomers considered up today. It is also an appealing alternative to typical photo- or thermal activation, allowing the efficient synthesis of highly pure organic materials.

Theoretical study of water-gas shift reaction on the silver nanocluster

NASA Astrophysics Data System (ADS)

Arab, Ali; Sharafie, Darioush; Fazli, Mostafa

2017-10-01

The kinetics of water gas shift reaction (WGSR) on the silver nanocluster was investigated using density functional theory according to the carboxyl associative mechanism. The hybrid B3PW91 functional along with the 6-31+G* and LANL2DZ basis sets were used throughout the calculations. It was observed that CO and H2O molecules adsorb physically on the Ag5 cluster without energy barrier as the initial steps of WGSR. The next three steps including H2Oads dissociation, carboxyl (OCOHads) formation, and CO2(ads) formation were accompanied by activation barrier. Transition states, as well as energy profiles of these three steps, were determined and analyzed. Our results revealed that the carboxyl and CO2(ads) formation were fast steps whereas H2Oads dissociation was the slowest step of WGSR.

3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships.

PubMed

Dhar, T G Murali; Shen, Zhongqi; Gu, Henry H; Chen, Ping; Norris, Derek; Watterson, Scott H; Ballentine, Shelley K; Fleener, Catherine A; Rouleau, Katherine A; Barrish, Joel C; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

2003-10-20

A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.

"There's so Much More to It than What I Initially Thought": Stepping into Researchers' Shoes with a Class Activity in a First Year Psychology Survey Course

ERIC Educational Resources Information Center

Tatlow-Golden, Mimi

2015-01-01

In psychology, it is widely agreed that research methods, although central to the discipline, are particularly challenging to learn and teach, particularly at introductory level. This pilot study explored the potential of embedding a student-conducted research activity in a one-semester undergraduate "Introduction to Psychology" survey…

A double-blind randomized discontinuation phase II study of sorafenib (BAY 43-9006) in previously treated non-small cell lung cancer patients: Eastern Cooperative Oncology Group study E2501

PubMed Central

Wakelee, Heather A.; Lee, Ju-Whei; Hanna, Nasser H.; Traynor, Anne M.; Carbone, David P.; Schiller, Joan H.

2012-01-01

Introduction Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase II study in heavily pretreated non-small cell lung cancer (NSCLC) patients (≥ two prior therapies) utilized a randomized discontinuation design. Methods Patients received 400 mg of sorafenib orally twice daily for two cycles (two months) (Step 1). Responding patients on Step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (Step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease two months after randomization. Results : There were 299 patients evaluated for Step 1 with 81 eligible patients randomized on Step 2 who received sorafenib (n=50) or placebo (n=31). The two-month disease control rates following randomization were 54% and 23% for patients initially receiving sorafenib and placebo respectively, p=0.005. The hazard ratio for progression on Step 2 was 0.51 (95% CI 0.30, 0.87, p=0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), HR 0.67 (95% CI 0.40-1.11), p=0.117. A dispensing error occurred which resulted in unblinding of some patients, but not before completion of the 8 week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions : The results of this randomized discontinuation trial suggest that sorafenib has single agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC. PMID:22982658

Clinical grade isolation of regulatory T cells from G-CSF mobilized peripheral blood improves with initial depletion of monocytes

PubMed Central

Patel, Pritesh; Mahmud, Dolores; Park, Youngmin; Yoshinaga, Kazumi; Mahmud, Nadim; Rondelli, Damiano

2015-01-01

Clinical isolation of circulating CD4+CD25+ regulatory T cells (Tregs) from peripheral blood mononuclear cells is usually performed by CD4+ cell negative selection followed by CD25+ cell positive selection. Although G-CSF mobilized peripheral blood (G-PBSC) contains a high number of Tregs, a high number of monocytes in G-PBSC limits Treg isolation. Using a small scale device (MidiMACS, Miltenyi) we initially demonstrated that an initial depletion of monocytes would be necessary to obtaina separation of CD4+CD25+FoxP3+CD127- cells from G-PBSC (G-Tregs) with a consistent purity >70% and inhibitory activity of T cell alloreactivity in-vitro. We then validated the same approach in a clinical scale setting by separating G-Tregs with clinically available antibodies to perform a CD8+CD19+CD14+ cell depletion followed by CD25+ cell selection (2-step process) or by adding an initial CD14+ cell depletion (3-step process) using a CliniMACS column. The 3-step approach resulted in a better purity (81±12% vs. 35±33%) and yield (66% vs. 39%). Clinically isolated G-Tregs were also FoxP3+CD127dim and functionally suppressive in-vitro. Our findings suggest that a better and more consistent purity of Tregs can be achieved from G-PBSC by an initial single depletion of monocytes prior to selection of CD4+CD25+ cells. PMID:27069755

School-Business Partnerships: Trojan Horse or Manna from Heaven?

ERIC Educational Resources Information Center

Burke, Michael A.

1986-01-01

Recent national initiatives have renewed interest in the development of cooperative programs involving participation by businesses in school activities. This article reviews potential problems and benefits in school-business partnerships and identifies six steps that must be followed if such partnerships are to be successful. (PGD)

[Comparison between one-step and two-step space closing methods of sliding mechanics using three-dimensional finite element].

PubMed

Han, Yaohui; Mou, Lan; Xu, Gengchi; Yang, Yiqiang; Ge, Zhenlin

2015-03-01

To construct a three-dimensional finite element model comparing between one-step and two-step methods in torque control of anterior teeth during space closure. Dicom image data including maxilla and upper teeth were obtained though cone-beam CT. A three-dimensional model was set up and the maxilla, upper teeth and periodontium were separated using Mimics software. The models were instantiated using Pro/Engineer software, and Abaqus finite element analysis software was used to simulate the sliding mechanics by loading 1.47 Nforce on traction hooks with different heights (2, 4, 6, 8, 10, 12 and 14 mm, respectively) in order to compare the initial displacement between six maxillary anterior teeth (one-step method) and four maxillary anterior teeth (two-step method). When moving anterior teeth bodily, initial displacements of central incisors in two-step method and in one-step method were 29.26 × 10⁻⁶ mm and 15.75 × 10⁻⁶ mm, respectively. The initial displacements of lateral incisors in two-step method and in one-step method were 46.76 × 10(-6) mm and 23.18 × 10(-6) mm, respectively. Under the same amount of light force, the initial displacement of anterior teeth in two-step method was doubled compared with that in one-step method. The root and crown of the canine couldn't obtain the same amount of displacement in one-step method. Two-step method could produce more initial displacement than one-step method. Therefore, two-step method was easier to achieve torque control of the anterior teeth during space closure.

Training Rapid Stepping Responses in an Individual With Stroke

PubMed Central

Inness, Elizabeth L.; Komar, Janice; Biasin, Louis; Brunton, Karen; Lakhani, Bimal; McIlroy, William E.

2011-01-01

Background and Purpose Compensatory stepping reactions are important responses to prevent a fall following a postural perturbation. People with hemiparesis following a stroke show delayed initiation and execution of stepping reactions and often are found to be unable to initiate these steps with the more-affected limb. This case report describes a targeted training program involving repeated postural perturbations to improve control of compensatory stepping in an individual with stroke. Case Description Compensatory stepping reactions of a 68-year-old man were examined 52 days after left hemorrhagic stroke. He required assistance to prevent a fall in all trials administered during his initial examination because he showed weight-bearing asymmetry (with more weight borne on the more-affected right side), was unable to initiate stepping with the right leg (despite blocking of the left leg in some trials), and demonstrated delayed response times. The patient completed 6 perturbation training sessions (30–60 minutes per session) that aimed to improve preperturbation weight-bearing symmetry, to encourage stepping with the right limb, and to reduce step initiation and completion times. Outcomes Improved efficacy of compensatory stepping reactions with training and reduced reliance on assistance to prevent falling were observed. Improvements were noted in preperturbation asymmetry and step timing. Blocking the left foot was effective in encouraging stepping with the more-affected right foot. Discussion This case report demonstrates potential short-term adaptations in compensatory stepping reactions following perturbation training in an individual with stroke. Future work should investigate the links between improved compensatory step characteristics and fall risk in this vulnerable population. PMID:21511992

Continuous Activity Monitoring During Concurrent Chemoradiotherapy

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

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Kabarriti, Rafi; Bodner, William R.

Purpose: To perform a prospective trial testing the feasibility and utility of acquiring activity data as a measure of health status during concurrent chemoradiotherapy. Methods and Materials: Ambulatory patients who were planned for treatment with concurrent chemoradiotherapy with curative intent for cancers of the head and neck, lung, or gastrointestinal tract were provided with activity monitors before treatment initiation. Patients were asked to wear the devices continuously throughout the radiation therapy course. Step count data were downloaded weekly during radiation therapy and 2 and 4 weeks after radiation therapy completion. The primary objective was to demonstrate feasibility, defined as collection ofmore » step counts for 80% of the days during study subjects' radiation therapy courses. Secondary objectives included establishing step count as a dynamic predictor of unplanned hospitalization risk. Results: Thirty-eight enrolled patients were treated with concurrent chemoradiotherapy. Primary diagnoses included head and neck cancer (n=11), lung cancer (n=13), and a variety of gastrointestinal cancers (n=14). Step data were collected for 1524 of 1613 days (94%) during patients' radiation therapy courses. Fourteen patients were hospitalized during radiation therapy or within 4 weeks of radiation therapy completion. Cox regression modeling demonstrated a significant association between recent step counts (3-day average) and hospitalization risk, with a 38% reduction in the risk of hospitalization for every 1000 steps taken each day (hazard ratio 0.62, 95% confidence interval 0.46-0.83, P=.002). Inferior quality of life scores and impaired performance status were not associated with increased hospitalization risk. Conclusion: Continuous activity monitoring during concurrent chemoradiotherapy is feasible and well-tolerated. Step counts may serve as powerful, objective, and dynamic indicators of hospitalization risk.« less

Extracellular annexins and dynamin are important for sequential steps in myoblast fusion

PubMed Central

Leikina, Evgenia; Melikov, Kamran; Sanyal, Sarmistha; Verma, Santosh K.; Eun, Bokkee; Gebert, Claudia; Pfeifer, Karl; Lizunov, Vladimir A.; Kozlov, Michael M.

2013-01-01

Myoblast fusion into multinucleated myotubes is a crucial step in skeletal muscle development and regeneration. Here, we accumulated murine myoblasts at the ready-to-fuse stage by blocking formation of early fusion intermediates with lysophosphatidylcholine. Lifting the block allowed us to explore a largely synchronized fusion. We found that initial merger of two cell membranes detected as lipid mixing involved extracellular annexins A1 and A5 acting in a functionally redundant manner. Subsequent stages of myoblast fusion depended on dynamin activity, phosphatidylinositol(4,5)bisphosphate content, and cell metabolism. Uncoupling fusion from preceding stages of myogenesis will help in the analysis of the interplay between protein machines that initiate and complete cell unification and in the identification of additional protein players controlling different fusion stages. PMID:23277424

Automatic 3D kidney segmentation based on shape constrained GC-OAAM

NASA Astrophysics Data System (ADS)

Chen, Xinjian; Summers, Ronald M.; Yao, Jianhua

2011-03-01

The kidney can be classified into three main tissue types: renal cortex, renal medulla and renal pelvis (or collecting system). Dysfunction of different renal tissue types may cause different kidney diseases. Therefore, accurate and efficient segmentation of kidney into different tissue types plays a very important role in clinical research. In this paper, we propose an automatic 3D kidney segmentation method which segments the kidney into the three different tissue types: renal cortex, medulla and pelvis. The proposed method synergistically combines active appearance model (AAM), live wire (LW) and graph cut (GC) methods, GC-OAAM for short. Our method consists of two main steps. First, a pseudo 3D segmentation method is employed for kidney initialization in which the segmentation is performed slice-by-slice via a multi-object oriented active appearance model (OAAM) method. An improved iterative model refinement algorithm is proposed for the AAM optimization, which synergistically combines the AAM and LW method. Multi-object strategy is applied to help the object initialization. The 3D model constraints are applied to the initialization result. Second, the object shape information generated from the initialization step is integrated into the GC cost computation. A multi-label GC method is used to segment the kidney into cortex, medulla and pelvis. The proposed method was tested on 19 clinical arterial phase CT data sets. The preliminary results showed the feasibility and efficiency of the proposed method.

The amino terminal extension of mammalian mitochondrial RNA polymerase ensures promoter specific transcription initiation

PubMed Central

Posse, Viktor; Hoberg, Emily; Dierckx, Anke; Shahzad, Saba; Koolmeister, Camilla; Larsson, Nils-Göran; Wilhelmsson, L. Marcus; Hällberg, B. Martin; Gustafsson, Claes M.

2014-01-01

Mammalian mitochondrial transcription is executed by a single subunit mitochondrial RNA polymerase (Polrmt) and its two accessory factors, mitochondrial transcription factors A and B2 (Tfam and Tfb2m). Polrmt is structurally related to single-subunit phage RNA polymerases, but it also contains a unique N-terminal extension (NTE) of unknown function. We here demonstrate that the NTE functions together with Tfam to ensure promoter-specific transcription. When the NTE is deleted, Polrmt can initiate transcription in the absence of Tfam, both from promoters and non-specific DNA sequences. Additionally, when in presence of Tfam and a mitochondrial promoter, the NTE-deleted mutant has an even higher transcription activity than wild-type polymerase, indicating that the NTE functions as an inhibitory domain. Our studies lead to a model according to which Tfam specifically recruits wild-type Polrmt to promoter sequences, relieving the inhibitory effect of the NTE, as a first step in transcription initiation. In the second step, Tfb2m is recruited into the complex and transcription is initiated. PMID:24445803

Land Ecology Essay I: The siren song of the finish line

USDA-ARS?s Scientific Manuscript database

As the National Cooperative Soils Survey nears the completion of initial mapping and description activities, the options for next steps are being considered. One option is to deploy new and emerging mapping technologies for existing and refined concepts of soil behavior to create more precise maps ...

Real time detection of ESKAPE pathogens by a nitroreductase-triggered fluorescence turn-on probe.

PubMed

Xu, Shengnan; Wang, Qinghua; Zhang, Qingyang; Zhang, Leilei; Zuo, Limin; Jiang, Jian-Dong; Hu, Hai-Yu

2017-10-18

The identification of bacterial pathogens is the critical first step in conquering infection diseases. A novel turn-on fluorescent probe for the selective sensing of nitroreductase (NTR) activity and its initial applications in rapid, real-time detection and identification of ESKAPE pathogens have been reported.

Stoichiometric network constraints on xylose metabolism by recombinant Saccharomyces cerevisiae

Treesearch

Yong-Su Jin; Thomas W. Jeffries

2004-01-01

Metabolic pathway engineering is constrained by the thermodynamic and stoichiometric feasibility of enzymatic activities of introduced genes. Engineering of xylose metabolism in Saccharomyces cerevisiae has focused on introducing genes for the initial xylose assimilation steps from Pichia stipitis, a xylose-fermenting yeast, into S. cerevisiae, a yeast raditionally...

Metatranscriptome of an Anaerobic Benzene-Degrading, Nitrate-Reducing Enrichment Culture Reveals Involvement of Carboxylation in Benzene Ring Activation

PubMed Central

Luo, Fei; Gitiafroz, Roya; Devine, Cheryl E.; Gong, Yunchen; Hug, Laura A.; Raskin, Lutgarde

2014-01-01

The enzymes involved in the initial steps of anaerobic benzene catabolism are not known. To try to elucidate this critical step, a metatranscriptomic analysis was conducted to compare the genes transcribed during the metabolism of benzene and benzoate by an anaerobic benzene-degrading, nitrate-reducing enrichment culture. RNA was extracted from the mixed culture and sequenced without prior mRNA enrichment, allowing simultaneous examination of the active community composition and the differential gene expression between the two treatments. Ribosomal and mRNA sequences attributed to a member of the family Peptococcaceae from the order Clostridiales were essentially only detected in the benzene-amended culture samples, implicating this group in the initial catabolism of benzene. Genes similar to each of two subunits of a proposed benzene-carboxylating enzyme were transcribed when the culture was amended with benzene. Anaerobic benzoate degradation genes from strict anaerobes were transcribed only when the culture was amended with benzene. Genes for other benzoate catabolic enzymes and for nitrate respiration were transcribed in both samples, with those attributed to an Azoarcus species being most abundant. These findings indicate that the mineralization of benzene starts with its activation by a strict anaerobe belonging to the Peptococcaceae, involving a carboxylation step to form benzoate. These data confirm the previously hypothesized syntrophic association between a benzene-degrading Peptococcaceae strain and a benzoate-degrading denitrifying Azoarcus strain for the complete catabolism of benzene with nitrate as the terminal electron acceptor. PMID:24795366

Evaluating Machine Learning–Based Automated Personalized Daily Step Goals Delivered Through a Mobile Phone App: Randomized Controlled Trial

PubMed Central

Zhou, Mo; Fukuoka, Yoshimi; Mintz, Yonatan; Goldberg, Ken; Kaminsky, Philip; Flowers, Elena

2018-01-01

Background Growing evidence shows that fixed, nonpersonalized daily step goals can discourage individuals, resulting in unchanged or even reduced physical activity. Objective The aim of this randomized controlled trial (RCT) was to evaluate the efficacy of an automated mobile phone–based personalized and adaptive goal-setting intervention using machine learning as compared with an active control with steady daily step goals of 10,000. Methods In this 10-week RCT, 64 participants were recruited via email announcements and were required to attend an initial in-person session. The participants were randomized into either the intervention or active control group with a one-to-one ratio after a run-in period for data collection. A study-developed mobile phone app (which delivers daily step goals using push notifications and allows real-time physical activity monitoring) was installed on each participant’s mobile phone, and participants were asked to keep their phone in a pocket throughout the entire day. Through the app, the intervention group received fully automated adaptively personalized daily step goals, and the control group received constant step goals of 10,000 steps per day. Daily step count was objectively measured by the study-developed mobile phone app. Results The mean (SD) age of participants was 41.1 (11.3) years, and 83% (53/64) of participants were female. The baseline demographics between the 2 groups were similar (P>.05). Participants in the intervention group (n=34) had a decrease in mean (SD) daily step count of 390 (490) steps between run-in and 10 weeks, compared with a decrease of 1350 (420) steps among control participants (n=30; P=.03). The net difference in daily steps between the groups was 960 steps (95% CI 90-1830 steps). Both groups had a decrease in daily step count between run-in and 10 weeks because interventions were also provided during run-in and no natural baseline was collected. Conclusions The results showed the short-term efficacy of this intervention, which should be formally evaluated in a full-scale RCT with a longer follow-up period. Trial Registration ClinicalTrials.gov: NCT02886871; https://clinicaltrials.gov/ct2/show/NCT02886871 (Archived by WebCite at http://www.webcitation.org/6wM1Be1Ng). PMID:29371177

Rapid Two-Step Procedure for Large-Scale Purification of Pediocin-Like Bacteriocins and Other Cationic Antimicrobial Peptides from Complex Culture Medium

PubMed Central

Uteng, Marianne; Hauge, Håvard Hildeng; Brondz, Ilia; Nissen-Meyer, Jon; Fimland, Gunnar

2002-01-01

A rapid and simple two-step procedure suitable for both small- and large-scale purification of pediocin-like bacteriocins and other cationic peptides has been developed. In the first step, the bacterial culture was applied directly on a cation-exchange column (1-ml cation exchanger per 100-ml cell culture). Bacteria and anionic compounds passed through the column, and cationic bacteriocins were subsequently eluted with 1 M NaCl. In the second step, the bacteriocin fraction was applied on a low-pressure, reverse-phase column and the bacteriocins were detected as major optical density peaks upon elution with propanol. More than 80% of the activity that was initially in the culture supernatant was recovered in both purification steps, and the final bacteriocin preparation was more than 90% pure as judged by analytical reverse-phase chromatography and capillary electrophoresis. PMID:11823243

Preliminary efficacy of prize-based contingency management to increase activity levels in healthy adults.

PubMed

Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L

2014-01-01

An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity. © Society for the Experimental Analysis of Behavior.

Antitumor Activity and Mechanism of Action of the Cyclopenta[b]benzofuran, Silvestrol

PubMed Central

Cencic, Regina; Carrier, Marilyn; Galicia-Vázquez, Gabriela; Bordeleau, Marie-Eve; Sukarieh, Rami; Bourdeau, Annie; Brem, Brigitte; Teodoro, Jose G.; Greger, Harald; Tremblay, Michel L.; Porco, John A.; Pelletier, Jerry

2009-01-01

Background Flavaglines are a family of natural products from the genus Aglaia that exhibit anti-cancer activity in vitro and in vivo and inhibit translation initiation. They have been shown to modulate the activity of eIF4A, the DEAD-box RNA helicase subunit of the eukaryotic initiation factor (eIF) 4F complex, a complex that stimulates ribosome recruitment during translation initiation. One flavagline, silvestrol, is capable of modulating chemosensitivity in a mechanism-based mouse model. Methodology/Principal Findings Among a number of flavagline family members tested herein, we find that silvestrol is the more potent translation inhibitor among these. We find that silvestrol impairs the ribosome recruitment step of translation initiation by affecting the composition of the eukaryotic initiation factor (eIF) 4F complex. We show that silvestrol exhibits significant anticancer activity in human breast and prostate cancer xenograft models, and that this is associated with increased apoptosis, decreased proliferation, and inhibition of angiogenesis. We demonstrate that targeting translation by silvestrol results in preferential inhibition of weakly initiating mRNAs. Conclusions/Significance Our results indicate that silvestrol is a potent anti-cancer compound in vivo that exerts its activity by affecting survival pathways as well as angiogenesis. We propose that silvestrol mediates its effects by preferentially inhibiting translation of malignancy-related mRNAs. Silvestrol appears to be well tolerated in animals. PMID:19401772

Phospholipase A2 from Bothrops alternatus (víbora de la cruz) venom. Purification and some characteristic properties.

PubMed

Nisenbom, H E; Seki, C; Vidal, J C

1986-01-01

One single protein species with phospholipase activity has been isolated from Bothrops alternatus venom by a procedure involving gel-filtration on Sephadex G-50 (Step 1), chromatography on SP-Sephadex C-50 (Step 2) and gel-filtration on Sephadex G-75 (Step 3). The purified sample behaved as a homogeneous, monodisperse protein with a molecular weight of 15,000 and isoelectric point of 5.04. The yield in enzyme activity was 48% of the starting material and the apparent purification was 51-fold. When assayed on 1,2-diheptanoyl- or 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine, fatty acids and lysolecithins were the only reaction products, in accordance with the predicted stoichiometry. Studies on positional specificity suggested that the enzyme is a phospholipase A2. The enzyme requires Ca2+ ions for activity and exhibited stereochemical specificity, since the enantiomeric 2, 3-diheptanoyl-sn-glycero-1-phosphorylcholine was not hydrolyzed. Under the experimental conditions employed, reaction products representative of either phospholipase B or C activities could not be detected. After Step 1, the phospholipase activity recovered was higher than the total activity in the crude venom sample, which is explained by the separation of an inhibitor during enzyme purification. The inhibitor was responsible for the initial lag period that characterized the kinetics of the enzyme reaction with crude venom acting on aggregated substrates (lipoprotein, vesicles or micelles), while the rate of hydrolysis of monomeric lecithins was not affected.

11-Step Total Synthesis of (−)-Maoecrystal V

PubMed Central

2016-01-01

An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (−)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product. PMID:27457680

Initiation of movement from quiet stance: comparison of gait and stepping in elderly subjects of different levels of functional ability.

PubMed

Brunt, Denis; Santos, Valeria; Kim, Hyeong Dong; Light, Kathye; Levy, Charles

2005-04-01

This study describes how elderly subjects initiate gait, and step from a position of quiet stance. Based on scores from selected standardized tests subjects were placed in either a high (HFL) or low functional level (LFL) group and were asked to initiate gait, step onto a 10 cm high, 1.22 m wide curb and step over a 10 cm high, 9 cm wide obstacle at a self paced speed. Stepping conditions affected the velocity of movement. It was clear that all subjects decreased initiation velocity for both curb and obstacle compared to gait initiation. Swing and stance limb acceleration ground reaction forces and EMG amplitude were modulated according to initiation velocity. Toe clearance was greater for obstacle than curb and gait initiation. Swing toe-off was significantly earlier and there was a trend for obstacle clearance to be greater for the HFL group. Those in the LFL group appear to be at a greater risk for falling due to the possible effect of slower rate of toe-off that could influence toe clearance over the obstacle.

Basic Skills Resource Center: A Descriptive Study of Learning Strategy Applications by English-as a-Second-Langage Students and Teachers in the Army

DTIC Science & Technology

1985-05-01

collection activity is presented in Table 1. Initial classroom observation of ESL classes was undertaken to familiarize researchers with the DLI curriculum...initiative. However, no student was observed asking another for information or clarification. Only in one classroom observation were the soldiers...one classroom observation where the soldiers were required to perform the steps involved in caring for and maintaining a gas mask was enlightening, for

Assessing NLRP3 Inflammasome Activation by Nanoparticles.

PubMed

Sharma, Bhawna; McLeland, Christopher B; Potter, Timothy M; Stern, Stephan T; Adiseshaiah, Pavan P

2018-01-01

NLRP3 inflammasome activation is one of the initial steps in an inflammatory cascade against pathogen/danger-associated molecular patterns (PAMPs/DAMPs), such as those arising from environmental toxins or nanoparticles, and is essential for innate immune response. NLRP3 inflammasome activation in cells can lead to the release of IL-1β cytokine via caspase-1, which is required for inflammatory-induced programmed cell death (pyroptosis). Nanoparticles are commonly used as vaccine adjuvants and drug delivery vehicles to improve the efficacy and reduce the toxicity of chemotherapeutic agents. Several studies indicate that different nanoparticles (e.g., liposomes, polymer-based nanoparticles) can induce NLRP3 inflammasome activation. Generation of a pro-inflammatory response is beneficial for vaccine delivery to provide adaptive immunity, a necessary step for successful vaccination. However, similar immune responses for intravenously injected, drug-containing nanoparticles can result in immunotoxicity (e.g., silica nanoparticles). Evaluation of NLRP3-mediated inflammasome activation by nanoparticles may predict pro-inflammatory responses in order to determine if these effects may be mitigated for drug delivery or optimized for vaccine development. In this protocol, we outline steps to monitor the release of IL-1β using PMA-primed THP-1 cells, a human monocytic leukemia cell line, as a model system. IL-1β release is used as a marker of NLRP3 inflammasome activation.

mHealth Physical Activity Intervention: A Randomized Pilot Study in Physically Inactive Pregnant Women.

PubMed

Choi, JiWon; Lee, Ji Hyeon; Vittinghoff, Eric; Fukuoka, Yoshimi

2016-05-01

Physical inactivity is prevalent in pregnant women, and innovative strategies to promote physical activity are strongly needed. The purpose of the study was to test a 12-week mobile health (mHealth) physical activity intervention for feasibility and potential efficacy. Participants were recruited between December 2012 and February 2014 using diverse recruitment methods. Thirty pregnant women between 10 and 20 weeks of gestation were randomized to an intervention (mobile phone app plus Fitbit) or a control (Fitbit) group. Both conditions targeted gradual increases in physical activity. The mHealth intervention included daily messages and a mobile phone activity diary with automated feedback and self-monitoring systems. On monthly average, 4 women were screened for initial eligibility by telephone and 2.5 were randomized. Intervention participants had a 1096 ± 1898 step increase in daily steps compared to an increase of 259 ± 1604 steps in control participants at 12 weeks. The change between groups in weekly mean steps per day during the 12-week study period was not statistically significant (p = 0.38). The intervention group reported lower perceived barrier to being active, lack of energy, than the control group at 12-week visit (p = 0.02). The rates of responding to daily messages and using the daily diary through the mobile app declined during the 12 week study period. It was difficult to recruit and randomize inactive women who wanted to increase physical activity during pregnancy. Pregnant women who were motivated to increase physical activity might find using mobile technologies in assessing and promoting PA acceptable. Possible reasons for the non-significant treatment effect of the mHealth intervention on physical activity are discussed. Public awareness of safety and benefits of physical activity during pregnancy should be promoted. Clinicaltrials.Gov Identifier NCT01461707.

KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps

NASA Astrophysics Data System (ADS)

Barro-Soria, Rene; Rebolledo, Santiago; Liin, Sara I.; Perez, Marta E.; Sampson, Kevin J.; Kass, Robert S.; Larsson, H. Peter

2014-04-01

The functional properties of KCNQ1 channels are highly dependent on associated KCNE-β subunits. Mutations in KCNQ1 or KCNE subunits can cause congenital channelopathies, such as deafness, cardiac arrhythmias and epilepsy. The mechanism by which KCNE1-β subunits slow the kinetics of KCNQ1 channels is a matter of current controversy. Here we show that KCNQ1/KCNE1 channel activation occurs in two steps: first, mutually independent voltage sensor movements in the four KCNQ1 subunits generate the main gating charge movement and underlie the initial delay in the activation time course of KCNQ1/KCNE1 currents. Second, a slower and concerted conformational change of all four voltage sensors and the gate, which opens the KCNQ1/KCNE1 channel. Our data show that KCNE1 divides the voltage sensor movement into two steps with widely different voltage dependences and kinetics. The two voltage sensor steps in KCNQ1/KCNE1 channels can be pharmacologically isolated and further separated by a disease-causing mutation.

Thermal denaturation of β-glucosidase B from Paenibacillus polymyxa proceeds through a Lumry-Eyring mechanism.

PubMed

Camarillo-Cadena, Menandro; Garza-Ramos, Georgina; Peimbert, Mariana; Pérez-Hernández, Gerardo; Zubillaga, Rafael A

2011-06-01

β-glucosidase B (BglB), 1,4-β-D: -glucanohydrolase, is an enzyme with various technological applications for which some thermostable mutants have been obtained. Because BglB denatures irreversibly with heating, the stabilities of these mutants are assessed kinetically. It, therefore, becomes relevant to determine whether the measured rate constants reflect one or several elementary kinetic steps. We have analyzed the kinetics of heat denaturation of BglB from Paenibacillus polymyxa under various conditions by following the loss of secondary structure and enzymatic activity. The denaturation is accompanied by aggregation and an initial reversible step at low temperatures. At T ≥ T ( m ), the process follows a two-state irreversible mechanism for which the kinetics does not depend on the enzyme concentration. This behavior can be explained by a Lumry-Eyring model in which the difference between the rates of the irreversible and the renaturation steps increases with temperature. Accordingly, at high scan rates (≥1 °C min(-1)) or temperatures (T ≥ T ( m )), the measurable activation energy involves only the elementary step of denaturation.

Complete Report on the Development of Welding Parameters for Irradiated Materials

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

Frederick, Greg; Sutton, Benjamin J.; Tatman, Jonathan K.

The advanced welding facility at the Radiochemical Engineering Development Center of Oak Ridge National Laboratory, which was conceived to enable research and development of weld repair techniques for nuclear power plant life extension, is now operational. The development of the facility and its advanced welding capabilities, along with the model materials for initial welding trials, were funded jointly by the U.S. Department of Energy, Office of Nuclear Energy, Light Water Reactor Sustainability Program, the Electric Power Research Institute, Long Term Operations Program and the Welding and Repair Technology Center, with additional support from Oak Ridge National Laboratory. Welding of irradiatedmore » materials was initiated on November 17, 2017, which marked a significant step in the development of the facility and the beginning of extensive welding research and development campaigns on irradiated materials that will eventually produce validated techniques and guidelines for weld repair activities carried out to extend the operational lifetimes of nuclear power plants beyond 60 years. This report summarizes the final steps that were required to complete weld process development, initial irradiated materials welding activities, near-term plans for irradiated materials welding, and plans for post-weld analyses that will be carried out to assess the ability of the advanced welding processes to make repairs on irradiated materials.« less

Frontal Joint Dynamics when Initiating Stair Ascent from a Walk versus a Stand

PubMed Central

Vallabhajosula, Srikant; Yentes, Jennifer M.; Stergiou, Nicholas

2011-01-01

Ascending stairs is a challenging activity of daily living for many populations. Frontal plane joint dynamics are critical to understand the mechanisms involved in stair ascension as they contribute to both propulsion and medio-lateral stability. However, previous research is limited to understanding these dynamics while initiating stair ascent from a stand. We investigated if initiating stair ascent from a walk with a comfortable self-selected speed could affect the frontal plane lower-extremity joint moments and powers as compared to initiating stair ascent from a stand and if this difference would exist at consecutive ipsilateral steps on the stairs. Kinematics data using a 3-D motion capture system and kinetics data using two force platforms on the first and third stair treads were recorded simultaneously as ten healthy young adults ascended a custom-built staircase. Data were collected from two starting conditions of stair ascent, from a walk (speed: 1.42±0.21m/s) and from a stand. Results showed that subjects generated greater peak knee abductor moment and greater peak hip abductor moment when initiating stair ascent from a walk. Greater peak joint moments and powers at all joints were also seen while ascending the second ipsilateral step. Particularly, greater peak hip abductor moment was needed to avoid contact of the contralateral limb with the intermediate step by counteracting the pelvic drop on the contralateral side. This could be important for therapists using stair climbing as a testing/training tool to evaluate hip strength in individuals with documented frontal plane abnormalities (i.e. knee and hip osteoarthritis, ACL injury). PMID:22172606

Accessory stimulus modulates executive function during stepping task

PubMed Central

Watanabe, Tatsunori; Koyama, Soichiro; Tanabe, Shigeo

2015-01-01

When multiple sensory modalities are simultaneously presented, reaction time can be reduced while interference enlarges. The purpose of this research was to examine the effects of task-irrelevant acoustic accessory stimuli simultaneously presented with visual imperative stimuli on executive function during stepping. Executive functions were assessed by analyzing temporal events and errors in the initial weight transfer of the postural responses prior to a step (anticipatory postural adjustment errors). Eleven healthy young adults stepped forward in response to a visual stimulus. We applied a choice reaction time task and the Simon task, which consisted of congruent and incongruent conditions. Accessory stimuli were randomly presented with the visual stimuli. Compared with trials without accessory stimuli, the anticipatory postural adjustment error rates were higher in trials with accessory stimuli in the incongruent condition and the reaction times were shorter in trials with accessory stimuli in all the task conditions. Analyses after division of trials according to whether anticipatory postural adjustment error occurred or not revealed that the reaction times of trials with anticipatory postural adjustment errors were reduced more than those of trials without anticipatory postural adjustment errors in the incongruent condition. These results suggest that accessory stimuli modulate the initial motor programming of stepping by lowering decision threshold and exclusively under spatial incompatibility facilitate automatic response activation. The present findings advance the knowledge of intersensory judgment processes during stepping and may aid in the development of intervention and evaluation tools for individuals at risk of falls. PMID:25925321

Activation Thermodynamics and H/D Kinetic Isotope Effect of the H ox to H red H + Transition in [FeFe] Hydrogenase

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

Ratzloff, Michael W.; Wilker, Molly B.; Mulder, David W.

Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here in this paper we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe. The H ox→H redH + reduction step measured by Fourier-transform infrared spectroscopy showed an enthalpy of activation of 19 kJ mol -1 and a ~2.5-foldmore » kinetic isotope effect. Overall these results support electron injection from CdSe into CaI involving F-clusters, and that the H ox→H redH + step of catalytic proton reduction in CaI proceeds by a proton-dependent process.« less

Activation Thermodynamics and H/D Kinetic Isotope Effect of the H ox to H red H + Transition in [FeFe] Hydrogenase

DOE PAGES

Ratzloff, Michael W.; Wilker, Molly B.; Mulder, David W.; ...

2017-08-29

Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here in this paper we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe. The H ox→H redH + reduction step measured by Fourier-transform infrared spectroscopy showed an enthalpy of activation of 19 kJ mol -1 and a ~2.5-foldmore » kinetic isotope effect. Overall these results support electron injection from CdSe into CaI involving F-clusters, and that the H ox→H redH + step of catalytic proton reduction in CaI proceeds by a proton-dependent process.« less

Extravehicular Activity Systems Education and Public Outreach in Support of NASA's STEM Initiatives

NASA Technical Reports Server (NTRS)

Paul, Heather L.

2011-01-01

The exploration activities associated with NASA?s goals to return to the Moon, travel to Mars, or explore Near Earth Objects (NEOs) will involve the need for human-supported space and surface extravehicular activities (EVAs). The technology development and human element associated with these exploration missions provide fantastic content to promote science, technology, engineering, and math (STEM). As NASA Administrator Charles F. Bolden remarked on December 9, 2009, "We....need to provide the educational and experiential stepping-stones to inspire the next generation of scientists, engineers, and leaders in STEM fields." The EVA Systems Project actively supports this initiative by providing subject matter experts and hands-on, interactive presentations to educate students, educators, and the general public about the design challenges encountered as NASA develops EVA hardware for these missions. This paper summarizes these education and public efforts.

The Southwest Oregon Research Project: Strengthening Coquille Sovereignty with Archival Research and Gift Giving

ERIC Educational Resources Information Center

Younker, Jason

2005-01-01

A personal and tribal history outlining the steps that the Coquille took to strengthen the claim to tribal sovereignty through investment in tribal education, active participation in academic research, and the reestablishment of relationships through gift giving is presented. Coquille scholars initiated the tribe's most successful endeavors, the…

Mother-Infant Activities: The Initial Step in Language Development in the Deaf-Blind Child.

ERIC Educational Resources Information Center

Vitagliano, James; Purdy, Susan

1987-01-01

The exploratory study examined the effectiveness of the Van Dijk method of developing language skills with four deaf-blind infants and their mothers over a two-month period. Findings indicated increased expressive/elocutionary communicative output with concomitant reduction in self-stimulatory, abusive, and tantrum-like behaviors. (DB)

A Wandering Mind Does Not Stray Far from Home: The Value of Metacognition in Distant Search

PubMed Central

Kudesia, Ravi S.; Baer, Markus; Elfenbein, Hillary Anger

2015-01-01

When faced with a problem, how do individuals search for potential solutions? In this article, we explore the cognitive processes that lead to local search (i.e., identifying options closest to existing solutions) and distant search (i.e., identifying options of a qualitatively different nature than existing solutions). We suggest that mind wandering is likely to lead to local search because it operates by spreading activation from initial ideas to closely associated ideas. This reduces the likelihood of accessing a qualitatively different solution. However, instead of getting lost in thought, individuals can also step back and monitor their thoughts from a detached perspective. Such mindful metacognition, we suggest, is likely to lead to distant search because it redistributes activation away from initial ideas to other, less strongly associated, ideas. This hypothesis was confirmed across two studies. Thus, getting lost in thoughts is helpful when one is on the right track and needs only a local search whereas stepping back from thoughts is helpful when one needs distant search to produce a change in perspective. PMID:25974164

Slipping during side-step cutting: anticipatory effects and familiarization.

PubMed

Oliveira, Anderson Souza Castelo; Silva, Priscila Brito; Lund, Morten Enemark; Farina, Dario; Kersting, Uwe Gustav

2014-04-01

The aim of the present study was to verify whether the expectation of perturbations while performing side-step cutting manoeuvres influences lower limb EMG activity, heel kinematics and ground reaction forces. Eighteen healthy men performed two sets of 90° side-step cutting manoeuvres. In the first set, 10 unperturbed trials (Base) were performed while stepping over a moveable force platform. In the second set, subjects were informed about the random possibility of perturbations to balance throughout 32 trials, of which eight were perturbed (Pert, 10cm translation triggered at initial contact), and the others were "catch" trials (Catch). Center of mass velocity (CoMVEL), heel acceleration (HAC), ground reaction forces (GRF) and surface electromyography (EMG) from lower limb and trunk muscles were recorded for each trial. Surface EMG was analyzed prior to initial contact (PRE), during load acceptance (LA) and propulsion (PRP) periods of the stance phase. In addition, hamstrings-quadriceps co-contraction ratios (CCR) were calculated for these time-windows. The results showed no changes in CoMVEL, HAC, peak GRF and surface EMG PRE among conditions. However, during LA, there were increases in tibialis anterior EMG (30-50%) concomitant to reduced EMG for quadriceps muscles, gluteus and rectus abdominis for Catch and Pert conditions (15-40%). In addition, quadriceps EMG was still reduced during PRP (p<.05). Consequently, CCR was greater for Catch and Pert in comparison to Base (p<.05). These results suggest that there is modulation of muscle activity towards anticipating potential instability in the lower limb joints and assure safety to complete the task. Copyright © 2014. Published by Elsevier B.V.

Genetic inactivation of Nrf2 prevents clonal expansion of initiated cells in a nutritional model of rat hepatocarcinogenesis.

PubMed

Orrù, Claudia; Szydlowska, Marta; Taguchi, Keiko; Zavattari, Patrizia; Perra, Andrea; Yamamoto, Masayuki; Columbano, Amedeo

2018-06-21

Dysregulation of the Keap1-Nrf2 pathway has been observed in experimental and human tumors, suggesting possible roles of the pathway in cancer development. Herein, we examined whether Nrf2 (Nfe2l2) activation occurs at early steps of rat hepatocarcinogenesis, to assess critical contributions of Nrf2 to the onset of hepatocellular carcinoma (HCC). We used wild-type (WT) and Nrf2 knockout (Nrf2KO) rats treated with a single injection of diethylnitrosamine (DENA) followed by choline-devoid methionine-deficient (CMD) diet. This experimental model causes massive fatty liver and steatohepatitis with fibrosis and enables identification of early stages of hepatocarcinogenesis. We found that Nrf2 activation takes place in early preneoplastic lesions identified by the marker glutathione S-transferase placental form (GSTP). Nrf2 missense mutations, known to disrupt the Keap1-Nrf2 binding, were present in 65.7% of GSTP-positive foci. Nrf2KO rats were used to directly investigate whether Nrf2 is critical for initiation and/or clonal expansion of DENA-damaged hepatocytes. While Nrf2 genetic inactivation did not alter DENA-induced initiation, it led to increased liver injury and chronic compensatory hepatocyte regeneration when rats were fed a CMD diet. However, in spite of such a permissive environment, the livers of Nrf2KO rats did not display any preneoplastic lesion unlike those of WT rats. These results demonstrate that, in a model of hepatocarcinogenesis resembling human non-alcoholic fatty liver disease: i) Nrf2 is activated at early steps of the tumorigenic process and ii) Nrf2 is mandatory for the clonal expansion of initiated cells, indicating that Nrf2 is critical in the onset of HCC. Dysregulation of the Keap1-Nrf2 molecular pathway has been observed in human tumors. In a nutritional model of hepatocarcinogenesis, the protein Nrf2 is frequently mutated/activated at early steps of the tumorigenic process. Herein, we show that Nrf2 is mandatory for the development of preneoplastic lesions. These results suggest that Nrf2 has a critical role in the onset of hepatocellular carcinoma. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

PubMed Central

Noordermeer, Daan; Leleu, Marion; Schorderet, Patrick; Joye, Elisabeth; Chabaud, Fabienne; Duboule, Denis

2014-01-01

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels. DOI: http://dx.doi.org/10.7554/eLife.02557.001 PMID:24843030

International Space Station (ISS) Risk Reduction Activities

NASA Technical Reports Server (NTRS)

Fodroci, Michael

2011-01-01

As the assembly of the ISS nears completion, it is worthwhile to step back and review some of the actions pursued by the Program in recent years to reduce risk and enhance the safety and health of ISS crewmembers, visitors, and space flight participants. While the ISS requirements and initial design were intended to provide the best practicable levels of safety, it is always possible to reduce risk -- given the determination and commitment to do so. The following is a summary of some of the steps taken by the ISS Program Manager, by our International Partners, by hardware and software designers, by operational specialists, and by safety personnel to continuously enhance the safety of the ISS. While decades of work went into developing the ISS requirements, there are many things in a Program like the ISS that can only be learned through actual operational experience. These risk reduction activities can be divided into roughly three categories: (1) Areas that were initially noncompliant which have subsequently been brought into compliance or near compliance (i.e., Micrometeoroid and Orbital Debris [MMOD] protection, acoustics) (2) Areas where initial design requirements were eventually considered inadequate and were subsequently augmented (i.e., Toxicity Level 4 materials, emergency hardware and procedures) (3) Areas where risks were initially underestimated, and have subsequently been addressed through additional mitigation (i.e., Extravehicular Activity [EVA] sharp edges, plasma shock hazards) Due to the hard work and cooperation of many parties working together across the span of nearly a decade, the ISS is now a safer and healthier environment for our crew, in many cases exceeding the risk reduction targets inherent in the intent of the original design. It will provide a safe and stable platform for utilization and discovery.

EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step

PubMed Central

Ninagawa, Satoshi; Okada, Tetsuya; Sumitomo, Yoshiki; Kamiya, Yukiko; Kato, Koichi; Horimoto, Satoshi; Ishikawa, Tokiro; Takeda, Shunichi; Sakuma, Tetsushi; Yamamoto, Takashi

2014-01-01

Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease–mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2. PMID:25092655

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics.

PubMed

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-07-21

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics

PubMed Central

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-01-01

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format. PMID:23685876

Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase.

PubMed

Lõoke, Marko; Maloney, Michael F; Bell, Stephen P

2017-02-01

Activation of the Mcm2-7 replicative DNA helicase is the committed step in eukaryotic DNA replication initiation. Although Mcm2-7 activation requires binding of the helicase-activating proteins Cdc45 and GINS (forming the CMG complex), an additional protein, Mcm10, drives initial origin DNA unwinding by an unknown mechanism. We show that Mcm10 binds a conserved motif located between the oligonucleotide/oligosaccharide fold (OB-fold) and A subdomain of Mcm2. Although buried in the interface between these domains in Mcm2-7 structures, mutations predicted to separate the domains and expose this motif restore growth to conditional-lethal MCM10 mutant cells. We found that, in addition to stimulating initial DNA unwinding, Mcm10 stabilizes Cdc45 and GINS association with Mcm2-7 and stimulates replication elongation in vivo and in vitro. Furthermore, we identified a lethal allele of MCM10 that stimulates initial DNA unwinding but is defective in replication elongation and CMG binding. Our findings expand the roles of Mcm10 during DNA replication and suggest a new model for Mcm10 function as an activator of the CMG complex throughout DNA replication. © 2017 Lõoke et al.; Published by Cold Spring Harbor Laboratory Press.

Physical activity intensity and health status perception of breast cancer patients undergoing adjuvant chemotherapy.

PubMed

Tonosaki, Akiko; Ishikawa, Miharu

2014-04-01

The aim was to evaluate the physical activity intensity (PAI) of patients receiving adjuvant chemotherapy and investigate the relationship between health status perception and PAI in Japan. Consenting participants of this prospective, descriptive, repeated measures design were 28 women aged 20-64 with stage I-IIIA initial breast cancer whose regimen included anthracycline. Participants wore a triaxial accelerometer and their PAI was measured for a 14-day period at the beginning of chemotherapy. The SF-36 Survey and Cancer Fatigue Scale were administered. The accelerometer was used to calculate the number of steps, physical activity level (PAL) and total minutes of PAI levels of under 1.5 Mets, 1.5-2.9 Mets, and more than 3.0 Mets during the first half (FH; days 2-7) and second half (SH; days 8-14) of the study. Data were analyzed using Pearson's correlation coefficient and multiple regression analysis. During FH, the mean number of steps was 3841.1 steps/day and mean PAL was 1.43; during SH, the mean number of steps was 4058.4 steps/day, mean PAL was 1.43; participants spent over 70% of the day working quietly in a sitting position. PAL during SH was significantly associated with mean time spent during activities of 1.5-2.9 Mets (β = 0.880, p < 0.0001) and 3.0 Mets (β = 0.268, p < 0.0001). Patients receiving adjuvant chemotherapy had extremely low physical activity. They should be provided useful information of appropriate physical movement and be supported in resolving physical and psychological distress. Copyright © 2013 Elsevier Ltd. All rights reserved.

A kinematic analysis of the rapid step test in balance-impaired and unimpaired older women.

PubMed

Schulz, Brian W; Ashton-Miller, James A; Alexander, Neil B

2007-04-01

Little is known about the kinematic and kinetic determinants that might explain age and balance-impairment alterations in the results of volitional stepping performance tests. Maximal unipedal stance time (UST) was used to distinguish "balance-impaired" old (BI, UST<10s, N=15, mean age=76 years) from unimpaired old (O, UST>30s, N=12, mean age=71 years) before they and healthy young females (Y, UST>30s, N=13, mean age=23 years) performed the rapid step test (RST). The RST evaluates the time required to take volitional front, side, and back steps of at least 80% maximum step length in response to verbal commands. Kinematic and kinetic data were recorded during the RST. The results indicate that the initiation phase of the step was the major source of age- and balance impairment-related delays. The delays in BI were primarily caused by increased postural adjustments prior to step initiation, as measured by center-of-pressure (COP) path length (p<0.003). The Step landing phase showed similar, but non-significant, temporal trends. Step length and peak center-of-mass (COM) deceleration during the Step-Out landing decreased in O by 18% (p=0.0002) and 24% (p=0.001), respectively, and a further 12% (p=0.04) and 18% (p=0.08) in BI. We conclude that the delay in BI step initiation was due to the increase in their postural adjustments prior to step initiation.

Variability of Anticipatory Postural Adjustments During Gait Initiation in Individuals With Parkinson Disease.

PubMed

Lin, Cheng-Chieh; Creath, Robert A; Rogers, Mark W

2016-01-01

In people with Parkinson disease (PD), difficulties with initiating stepping may be related to impairments of anticipatory postural adjustments (APAs). Increased variability in step length and step time has been observed in gait initiation in individuals with PD. In this study, we investigated whether the ability to generate consistent APAs during gait initiation is compromised in these individuals. Fifteen subjects with PD and 8 healthy control subjects were instructed to take rapid forward steps after a verbal cue. The changes in vertical force and ankle marker position were recorded via force platforms and a 3-dimensional motion capture system, respectively. Means, standard deviations, and coefficients of variation of both timing and magnitude of vertical force, as well as stepping variables, were calculated. During the postural phase of gait initiation the interval was longer and the force modulation was smaller in subjects with PD. Both the variability of timing and force modulation were larger in subjects with PD. Individuals with PD also had a longer time to complete the first step, but no significant differences were found for the variability of step time, length, and speed between groups. The increased variability of APAs during gait initiation in subjects with PD could affect posture-locomotion coupling, and lead to start hesitation, and even falls. Future studies are needed to investigate the effect of rehabilitation interventions on the variability of APAs during gait initiation in individuals with PD.Video abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A119).

Evaluating Machine Learning-Based Automated Personalized Daily Step Goals Delivered Through a Mobile Phone App: Randomized Controlled Trial.

PubMed

Zhou, Mo; Fukuoka, Yoshimi; Mintz, Yonatan; Goldberg, Ken; Kaminsky, Philip; Flowers, Elena; Aswani, Anil

2018-01-25

Growing evidence shows that fixed, nonpersonalized daily step goals can discourage individuals, resulting in unchanged or even reduced physical activity. The aim of this randomized controlled trial (RCT) was to evaluate the efficacy of an automated mobile phone-based personalized and adaptive goal-setting intervention using machine learning as compared with an active control with steady daily step goals of 10,000. In this 10-week RCT, 64 participants were recruited via email announcements and were required to attend an initial in-person session. The participants were randomized into either the intervention or active control group with a one-to-one ratio after a run-in period for data collection. A study-developed mobile phone app (which delivers daily step goals using push notifications and allows real-time physical activity monitoring) was installed on each participant's mobile phone, and participants were asked to keep their phone in a pocket throughout the entire day. Through the app, the intervention group received fully automated adaptively personalized daily step goals, and the control group received constant step goals of 10,000 steps per day. Daily step count was objectively measured by the study-developed mobile phone app. The mean (SD) age of participants was 41.1 (11.3) years, and 83% (53/64) of participants were female. The baseline demographics between the 2 groups were similar (P>.05). Participants in the intervention group (n=34) had a decrease in mean (SD) daily step count of 390 (490) steps between run-in and 10 weeks, compared with a decrease of 1350 (420) steps among control participants (n=30; P=.03). The net difference in daily steps between the groups was 960 steps (95% CI 90-1830 steps). Both groups had a decrease in daily step count between run-in and 10 weeks because interventions were also provided during run-in and no natural baseline was collected. The results showed the short-term efficacy of this intervention, which should be formally evaluated in a full-scale RCT with a longer follow-up period. ClinicalTrials.gov: NCT02886871; https://clinicaltrials.gov/ct2/show/NCT02886871 (Archived by WebCite at http://www.webcitation.org/6wM1Be1Ng). ©Mo Zhou, Yoshimi Fukuoka, Yonatan Mintz, Ken Goldberg, Philip Kaminsky, Elena Flowers, Anil Aswani. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 25.01.2018.

Accelerometer-based step initiation control for gait-assist neuroprostheses.

PubMed

Foglyano, Kevin M; Schnellenberger, John R; Kobetic, Rudi; Lombardo, Lisa; Pinault, Gilles; Selkirk, Stephen; Makowski, Nathaniel S; Triolo, Ronald J

2016-01-01

Electrical activation of paralyzed musculature can generate or augment joint movements required for walking after central nervous system trauma. Proper timing of stimulation relative to residual volitional control is critical to usefully affecting ambulation. This study evaluates three-dimensional accelerometers and customized algorithms to detect the intent to step from voluntary movements to trigger stimulation during walking in individuals with significantly different etiologies, mobility limitations, manual dexterities, and walking aids. Three individuals with poststroke hemiplegia or partial spinal cord injury exhibiting varying gait deficits were implanted with multichannel pulse generators to provide joint motions at the hip, knee, and ankle. An accelerometer integrated into the external control unit was used to detect heel strike or walker movement, and wireless accelerometers were used to detect crutch strike. Algorithms were developed for each sensor location to detect intent to step to progress through individualized stimulation patterns. Testing these algorithms produced detection accuracies of at least 90% on both level ground and uneven terrain. All participants use their accelerometer-triggered implanted gait systems in the community; the validation/system testing was completed in the hospital. The results demonstrated that safe, reliable, and convenient accelerometer-based step initiation can be achieved regardless of specific gait deficits, manual dexterities, and walking aids.

A two-step mechanism for stem cell activation during hair regeneration.

PubMed

Greco, Valentina; Chen, Ting; Rendl, Michael; Schober, Markus; Pasolli, H Amalia; Stokes, Nicole; Dela Cruz-Racelis, June; Fuchs, Elaine

2009-02-06

Hair follicles (HFs) undergo cyclic bouts of degeneration, rest, and regeneration. During rest (telogen), the hair germ (HG) appears as a small cell cluster between the slow-cycling bulge and dermal papilla (DP). Here we show that HG cells are derived from bulge stem cells (SCs) but become responsive quicker to DP-promoting signals. In vitro, HG cells also proliferate sooner but display shorter-lived potential than bulge cells. Molecularly, they more closely resemble activated bulge rather than transit-amplifying (matrix) cells. Transcriptional profiling reveals precocious activity of both HG and DP in late telogen, accompanied by Wnt signaling in HG and elevated FGFs and BMP inhibitors in DP. FGFs and BMP inhibitors participate with Wnts in exerting selective and potent stimuli to the HG both in vivo and in vitro. Our findings suggest a model where HG cells fuel initial steps in hair regeneration, while the bulge is the engine maintaining the process.

Asymmetric Total Synthesis of (-)-(3 R)-Inthomycin C.

PubMed

Balcells, Sandra; Haughey, Maxwell B; Walker, Johannes C L; Josa-Culleré, Laia; Towers, Christopher; Donohoe, Timothy J

2018-06-04

A short (10 step) and efficient (15% overall yield) synthesis of the natural product (-)-(3 R)-inthomycin C is reported. The key steps comprise three C-C bond-forming reactions: (i) a vinylogous Mukaiyama aldol, (ii) an olefin cross-metathesis reaction, and (iii) an asymmetric Mukaiyama-Kiyooka aldol. This route is notable for its brevity and has the advantage of lacking stoichiometric tin-promoted cross-coupling reactions present in previous approaches. Initial investigations on the biological activity of (-)-(3 R)-inthomycin C and structural analogues on human cancer cell lines are also described for the first time.

Stochastic model of template-directed elongation processes in biology.

PubMed

Schilstra, Maria J; Nehaniv, Chrystopher L

2010-10-01

We present a novel modular, stochastic model for biological template-based linear chain elongation processes. In this model, elongation complexes (ECs; DNA polymerase, RNA polymerase, or ribosomes associated with nascent chains) that span a finite number of template units step along the template, one after another, with semaphore constructs preventing overtaking. The central elongation module is readily extended with modules that represent initiation and termination processes. The model was used to explore the effect of EC span on motor velocity and dispersion, and the effect of initiation activator and repressor binding kinetics on the overall elongation dynamics. The results demonstrate that (1) motors that move smoothly are able to travel at a greater velocity and closer together than motors that move more erratically, and (2) the rate at which completed chains are released is proportional to the occupancy or vacancy of activator or repressor binding sites only when initiation or activator/repressor dissociation is slow in comparison with elongation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy

NASA Astrophysics Data System (ADS)

Rao, Yijian; Perna, Marco G.; Hofmann, Benjamin; Beier, Viola; Wollert, Thomas

2016-01-01

Autophagosomes are double-membrane vesicles that sequester cytoplasmic material for lysosomal degradation. Their biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. This process depends on the regulated activation of the Atg1-kinase complex. However, the underlying molecular mechanism remains unclear. Here we reconstitute this early step in autophagy from purified components in vitro. We find that on assembly from its cytoplasmic subcomplexes, the Atg1-kinase complex becomes activated, enabling it to recruit and tether Atg9-vesicles. The scaffolding protein Atg17 targets the Atg1-kinase complex to autophagic membranes by specifically recognizing the membrane protein Atg9. This interaction is inhibited by the two regulatory subunits Atg31 and Atg29. Engagement of the Atg1-Atg13 subcomplex restores the Atg9-binding and membrane-tethering activity of Atg17. Our data help to unravel the mechanism that controls Atg17-mediated tethering of Atg9-vesicles, providing the molecular basis to understand initiation of autophagosome-biogenesis.

It just doesn't speak to me: mid-aged men's reactions to '10,000 Steps a Day'.

PubMed

Burton, Nicola W; Walsh, Anthony; Brown, Wendy J

2008-04-01

The evaluation of an earlier 10,000 Steps community-based intervention program indicated that men were less likely than women to have used a pedometer or increased their physical activity (PA). This study aimed to explore men's reactions to the 10,000 Steps a Day message, the use of pedometers, and other strategies for increasing PA. Five focus groups were conducted with 39 men aged 45-65 years. Although many were familiar with the 10,000 Steps message, the majority of men did not like it. Pedometers were seen as useful for assessing PA in the short term, but not for ongoing use. Participants were generally aware of PA recommendations. Walking was considered a good option for this age group, but there was varying interest in this type of activity. Weight and stress management were commonly identified benefits of PA. Common barriers to PA were lack of time and motivation, health and weight restrictions, cost, and disinterest. Suggestions of how to promote PA to mid-aged men included workplace initiatives, making PA "fun", and creating opportunities for men to do PA with their family or same-aged peers. PA promotion using the 10,000 Steps message, walking, and pedometers may not appeal to mid-aged men.

Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation.

PubMed

Richard, Aliénor; Van Hamme, Angèle; Drevelle, Xavier; Golmard, Jean-Louis; Meunier, Sabine; Welter, Marie-Laure

2017-09-01

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Preventing Tooth Decay: A Guide for Implementing Self-Applied Fluoride in Schools.

ERIC Educational Resources Information Center

National Inst. of Dental Research (NIH), Bethesda, MD.

This guidebook was developed to assist citizens in initiating programs to prevent tooth decay in young children through the use of fluoridation. It contains outlines for determining the needs of the school and community for fluoride in drinking water, and presents the various steps and activities that are necessary for developing and implementing…

76 FR 51391 - Commercial Wind Lease Issuance and Site Characterization Activities on the Atlantic Outer...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... Environmental Assessment. SUMMARY: This notice is being published as an initial step for the purpose of... areas, in accordance with the DOI and the Council on Environmental Quality (CEQ) regulations implementing the provisions of the National Environmental Policy Act (NEPA) of 1969 as amended (42 U.S.C. 4321...

Understanding the barriers to crystal growth: dynamical simulation of the dissolution and growth of urea from aqueous solution.

PubMed

Piana, Stefano; Gale, Julian D

2005-02-16

Both the dissolution and growth of a molecular crystalline material, urea, has been studied using dynamical atomistic simulation. The kinetic steps of dissolution and growth are clearly identified, and the activation energies for each possible step are calculated. Our molecular dynamics simulations indicate that crystal growth on the [001] face is characterized by a nucleation and growth mechanism. Nucleation on the [001] urea crystal face is predicted to occur at a very high rate, followed by rapid propagation of the steps. The rate-limiting step for crystallization is actually found to be the removal of surface defects, rather than the initial formation of the next surface layer. Through kinetic Monte Carlo modeling of the surface growth, it is found that this crystal face evolves via a rough surface topography, rather than a clean layer-by-layer mechanism.

Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori.

PubMed

Tsugawa, Hitoshi; Suzuki, Hidekazu; Muraoka, Hiroe; Ikeda, Fumiaki; Hirata, Kenro; Matsuzaki, Juntaro; Saito, Yoshimasa; Hibi, Toshifumi

2011-01-14

Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori. Copyright © 2010 Elsevier Inc. All rights reserved.

An Initial Evaluation of the Impact of Pokémon GO on Physical Activity.

PubMed

Xian, Ying; Xu, Hanzhang; Xu, Haolin; Liang, Li; Hernandez, Adrian F; Wang, Tracy Y; Peterson, Eric D

2017-05-16

Pokémon GO is a location-based augmented reality game. Using GPS and the camera on a smartphone, the game requires players to travel in real world to capture animated creatures, called Pokémon. We examined the impact of Pokémon GO on physical activity (PA). A pre-post observational study of 167 Pokémon GO players who were self-enrolled through recruitment flyers or online social media was performed. Participants were instructed to provide screenshots of their step counts recorded by the iPhone Health app between June 15 and July 31, 2016, which was 3 weeks before and 3 weeks after the Pokémon GO release date. Of 167 participants, the median age was 25 years (interquartile range, 21-29 years). The daily average steps of participants at baseline was 5678 (SD, 2833; median, 5718 [interquartile range, 3675-7279]). After initiation of Pokémon GO, daily activity rose to 7654 steps (SD, 3616; median, 7232 [interquartile range, 5041-9744], pre-post change: 1976; 95% CI, 1494-2458, or a 34.8% relative increase [ P <0.001]). On average, 10 000 "XP" points (a measure of game progression) was associated with 2134 additional steps per day (95% CI, 1673-2595), suggesting a potential dose-response relationship. The number of participants achieving a goal of 10 000+ steps per day increased from 15.3% before to 27.5% after (odds ratio, 2.06; 95% CI, 1.70-2.50). Increased PA was also observed in subgroups, with the largest increases seen in participants who spent more time playing Pokémon GO, those who were overweight/obese, or those with a lower baseline PA level. Pokémon GO participation was associated with a significant increase in PA among young adults. Incorporating PA into gameplay may provide an alternative way to promote PA in persons who are attracted to the game. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02888314. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Sequence-dependent base pair stepping dynamics in XPD helicase unwinding

PubMed Central

Qi, Zhi; Pugh, Robert A; Spies, Maria; Chemla, Yann R

2013-01-01

Helicases couple the chemical energy of ATP hydrolysis to directional translocation along nucleic acids and transient duplex separation. Understanding helicase mechanism requires that the basic physicochemical process of base pair separation be understood. This necessitates monitoring helicase activity directly, at high spatio-temporal resolution. Using optical tweezers with single base pair (bp) resolution, we analyzed DNA unwinding by XPD helicase, a Superfamily 2 (SF2) DNA helicase involved in DNA repair and transcription initiation. We show that monomeric XPD unwinds duplex DNA in 1-bp steps, yet exhibits frequent backsteps and undergoes conformational transitions manifested in 5-bp backward and forward steps. Quantifying the sequence dependence of XPD stepping dynamics with near base pair resolution, we provide the strongest and most direct evidence thus far that forward, single-base pair stepping of a helicase utilizes the spontaneous opening of the duplex. The proposed unwinding mechanism may be a universal feature of DNA helicases that move along DNA phosphodiester backbones. DOI: http://dx.doi.org/10.7554/eLife.00334.001 PMID:23741615

The effect of pedometer use on physical activity and body weight in obese women.

PubMed

Cayir, Yasemin; Aslan, Secil Menekse; Akturk, Zekeriya

2015-01-01

Physical activity and healthy eating are of the utmost importance in treatment of obesity. However obese generally tend to have a sedentary lifestyle. Walking is a form of physical activity that is both simple and can be performed by everyone, but it requires an objective measurement. Number of steps taken during tracking can be recorded with the pedometer, a device used to measure the level of physical activity. We aimed to investigate whether or not using pedometers as a motivational technique to increase the level of physical activity in obese women has an impact on weight loss. Eighty-four obese women who are similar age referring to Ataturk University Faculty of Medicine Healthy Living Clinic, Turkey were randomly divided into two groups. Intervention group were given pedometers, and control group were prescribed similar diet and physical activity with a three-month follow-up plan without pedometers. Mean weight in pedometer group initially was 88.9 ± 8.4 kg, which decreased to 80.2 ± 8.7 kg after the programme. Mean weight in control group was 86.1 ± 9.2 kg at the beginning, and it decreased to 84.7 ± 8.8 kg after three months. It was observed in pedometer group that the mean number of steps 8817 ± 2725 steps/day at the beginning increased to mean 9716 ± 2811 steps/day at the end of the study. Weight, body mass index, body fat percentage and waist circumference measurements decreased more greatly in the pedometer when compared to the control group (p < 0.001). Pedometers may be recommended to obese patients to monitor and increase the level of physical activity and to promote weight loss.

Absence of equifinality of hand position in a double-step unloading task.

PubMed

Norouzi-Gheidari, Nahid; Archambault, Philippe

2010-08-01

Equifinality, during arm reaching movements, relates to the capacity of the neuromuscular system to attain the same final position in the presence or absence of transient perturbations. There have been several controversies regarding equifinality in the literature. A brief elastic perturbation, applied during a fast arm movement or just before its initiation, typically does not affect final arm position. On the other hand, several experiments have shown that velocity-dependent perturbations, such as Coriolis force or negative damping, while transient in nature, have a significant effect on final arm position when compared to unperturbed movements. In this study, an unloading paradigm was used to study the role of reflexes with respect to equifinality. The effects on final arm position of suddenly decreasing a static load maintained by fourteen subjects were analyzed. Subjects maintained an initial load produced by a double-joint manipulandum moving in the horizontal plane. The load was suddenly decreased, either in one or in two successive steps with different time intervals, resulting in a rapid reflex-mediated change in arm position. Unloading led to short-latency changes in the activity of shoulder and elbow muscles and significant variations in tonic activity. It was found that the final hand position was shorter for double- versus single-step unloading if the time between two successive changes in load was greater than 100 ms. With a shorter time interval, the final hand positions were the same. This difference in final hand positions was inversely proportional to the hand velocity at the time of the second change in load. Further, agonist/antagonist co-activation increased in double-step unloading. Thus, the change in both the load and the movement velocity may influence the magnitude of the unloading reflex. This may be indicative of a dependence of stretch reflexes on velocity. Perturbation may cause a reflex-mediated increase in joint stiffness, which could explain why equifinality is not preserved after some perturbations, such as velocity-dependant external forces.

Frontal joint dynamics when initiating stair ascent from a walk versus a stand.

PubMed

Vallabhajosula, Srikant; Yentes, Jennifer M; Stergiou, Nicholas

2012-02-02

Ascending stairs is a challenging activity of daily living for many populations. Frontal plane joint dynamics are critical to understand the mechanisms involved in stair ascension as they contribute to both propulsion and medio-lateral stability. However, previous research is limited to understanding these dynamics while initiating stair ascent from a stand. We investigated if initiating stair ascent from a walk with a comfortable self-selected speed could affect the frontal plane lower-extremity joint moments and powers as compared to initiating stair ascent from a stand and if this difference would exist at consecutive ipsilateral steps on the stairs. Kinematics data using a 3-D motion capture system and kinetics data using two force platforms on the first and third stair treads were recorded simultaneously as ten healthy young adults ascended a custom-built staircase. Data were collected from two starting conditions of stair ascent, from a walk (speed: 1.42 ± 0.21 m/s) and from a stand. Results showed that subjects generated greater peak knee abductor moment and greater peak hip abductor moment when initiating stair ascent from a walk. Greater peak joint moments and powers at all joints were also seen while ascending the second ipsilateral step. Particularly, greater peak hip abductor moment was needed to avoid contact of the contralateral limb with the intermediate step by counteracting the pelvic drop on the contralateral side. This could be important for therapists using stair climbing as a testing/training tool to evaluate hip strength in individuals with documented frontal plane abnormalities (i.e. knee and hip osteoarthritis, ACL injury). Copyright © 2011 Elsevier Ltd. All rights reserved.

Mesoporous-activated carbon prepared from chitosan flakes via single-step sodium hydroxide activation for the adsorption of methylene blue.

PubMed

Marrakchi, F; Ahmed, M J; Khanday, W A; Asif, M; Hameed, B H

2017-05-01

In this work, mesoporous-activated carbon (CSAC) was prepared from chitosan flakes (CS) via single-step sodium hydroxide activation for the adsorption of methylene blue (MB). CSAC was prepared using different impregnation ratios of NaOH:CS (1:1, 2:1, 3:1, and 4:1) at 800°C for 90min. The adsorption performance of CSAC was evaluated for MB at different adsorption variables, such MB initial concentrations (25-400mg/L), solution pH (3-11), and temperature (30-50°C). The adsorption isotherm data of CSAC-MB were well fitted to Langmuir model with a maximum adsorption capacity 143.53mg/g at 50°C. Best representation of kinetic data was obtained by the pseudo-second order model. CSAC exhibited excellent adsorption uptake for MB and can potentially be used for other cationic dyes. Copyright © 2017 Elsevier B.V. All rights reserved.

Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

PubMed

Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

1995-08-01

Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing.

PubMed

Barakat, Tahsin Stefan; Loos, Friedemann; van Staveren, Selma; Myronova, Elvira; Ghazvini, Mehrnaz; Grootegoed, J Anton; Gribnau, Joost

2014-03-20

X chromosome inactivation (XCI) in female placental mammals is a vital mechanism for dosage compensation between X-linked and autosomal genes. XCI starts with activation of Xist and silencing of the negative regulator Tsix, followed by cis spreading of Xist RNA over the future inactive X chromosome (Xi). Here, we show that XCI does not require physical contact between the two X chromosomes (X-pairing) but is regulated by trans-acting diffusible factors. We found that the X-encoded trans-acting and dose-dependent XCI-activator RNF12 acts in concert with the cis-regulatory region containing Jpx, Ftx, and Xpr to activate Xist and to overcome repression by Tsix. RNF12 acts at two subsequent steps; two active copies of Rnf12 drive initiation of XCI, and one copy needs to remain active to maintain XCI toward establishment of the Xi. This two-step mechanism ensures that XCI is very robust and fine-tuned, preventing XCI of both X chromosomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Dna2 initiates resection at clean DNA double-strand breaks

PubMed Central

Paudyal, Sharad C.; Li, Shan; Yan, Hong; Hunter, Tony

2017-01-01

Abstract Nucleolytic resection of DNA double-strand breaks (DSBs) is essential for both checkpoint activation and homology-mediated repair; however, the precise mechanism of resection, especially the initiation step, remains incompletely understood. Resection of blocked ends with protein or chemical adducts is believed to be initiated by the MRN complex in conjunction with CtIP through internal cleavage of the 5′ strand DNA. However, it is not clear whether resection of clean DSBs with free ends is also initiated by the same mechanism. Using the Xenopus nuclear extract system, here we show that the Dna2 nuclease directly initiates the resection of clean DSBs by cleaving the 5′ strand DNA ∼10–20 nucleotides away from the ends. In the absence of Dna2, MRN together with CtIP mediate an alternative resection initiation pathway where the nuclease activity of MRN apparently directly cleaves the 5′ strand DNA at more distal sites. MRN also facilitates resection initiation by promoting the recruitment of Dna2 and CtIP to the DNA substrate. The ssDNA-binding protein RPA promotes both Dna2- and CtIP–MRN-dependent resection initiation, but a RPA mutant can distinguish between these pathways. Our results strongly suggest that resection of blocked and clean DSBs is initiated via distinct mechanisms. PMID:28981724

Role of the σ 54 Activator Interacting Domain in Bacterial Transcription Initiation

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

Siegel, Alexander R.; Wemmer, David E.

Bacterial sigma factors are subunits of RNA polymerase that direct the holoenzyme to specific sets of promoters in the genome and are a central element of regulating transcription. Most polymerase holoenzymes open the promoter and initiate transcription rapidly after binding. However, polymerase containing the members of the σ 54 family must be acted on by a transcriptional activator before DNA opening and initiation occur. A key domain in these transcriptional activators forms a hexameric AAA + ATPase that acts through conformational changes brought on by ATP hydrolysis. Contacts between the transcriptional activator and σ 54 are primarily made through anmore » N-terminal σ 54 activator interacting domain (AID). To better understand this mechanism of bacterial transcription initiation, we characterized the σ 54 AID by NMR spectroscopy and other biophysical methods and show that it is an intrinsically disordered domain in σ 54 alone. In this paper, we identified a minimal construct of the Aquifex aeolicus σ 54 AID that consists of two predicted helices and retains native-like binding affinity for the transcriptional activator NtrC1. Using the NtrC1 ATPase domain, bound with the non-hydrolyzable ATP analog ADP-beryllium fluoride, we studied the NtrC1–σ 54 AID complex using NMR spectroscopy. We show that the σ 54 AID becomes structured after associating with the core loops of the transcriptional activators in their ATP state and that the primary site of the interaction is the first predicted helix. Finally, understanding this complex, formed as the first step toward initiation, will help unravel the mechanism of σ 54 bacterial transcription initiation.« less

Interfacial adhesion improvement in carbon fiber/carbon nanotube reinforced hybrid composites by the application of a reactive hybrid resin initiated by gamma irradiation

NASA Astrophysics Data System (ADS)

Szebényi, G.; Faragó, D.; Lámfalusi, Cs.; Göbl, R.

2018-04-01

Interfacial adhesion is a key factor in composite materials. The effective co-working of the reinforcing materials and matrix is essential for the proper load transfer between them, and to achieve the desired reinforcing effect. In case of nanocomposites, especially carbon nanotube (CNT) reinforced nanocomposites the adhesion between the CNTs and the polymer matrix is poor. To improve the interfacial adhesion and exploit the reinforcing effect of these nanoparticles a two step curable epoxy (EP)/vinylester (VE) hybrid resin system was developed where the EP is cured using hardener in the first step, during the composite production, and in the second step the curing of the VE is initiated by gamma irradiation, which also activates the reinforcing materials and the cured matrix component. A total of six carbon fiber reinforced composite systems were compared with neat epoxy and EP/VE hybrid matrices with and without chemical initiator and MWCNT nano-reinforcement. The effect of gamma irradiation was investigated at four absorbed dose levels. According to our three point bending and interlaminar shear test results the adhesion has improved between all constituents of the composite system. It was demonstrated that gamma irradiation has beneficial effect on the static mechanical, especially interlaminar properties of both micro- and nanocomposites in terms of modulus, strength and interlaminar shear strength.

Initiale Aktivität und Willkürverhalten bei Tieren

NASA Astrophysics Data System (ADS)

Heisenberg, Martin

1983-02-01

Initiation as a basic property of behavioral activity is functionally analyzed and discussed at the level of voluntary behavior. Fixed action patterns often are not released by stimuli but are generated by the animal itself through brain processes of the Darwinian type. Analogous to mutations, behavioral “subroutines” are brought up by chance and are subjected to selection either by the change in the situation (trial and the elimination of error) or by mental activity suppressing inappropriate behavior even before it is executed.Initiation improves the chance of survival. It is a prerequisite of goal-oriented behavior, an essential constituent of operant conditioning and presumably the first step in the evolution of thought. According to I. Kant a person is free if, by following his own directive, he does what has to be done. This definition meets the two central criteria of initiation: the independence of releasing stimuli and the adaptive value of the behavior generated.

Reactivation of stalled polyribosomes in synaptic plasticity

PubMed Central

Graber, Tyson E.; Hébert-Seropian, Sarah; Khoutorsky, Arkady; David, Alexandre; Yewdell, Jonathan W.; Lacaille, Jean-Claude; Sossin, Wayne S.

2013-01-01

Some forms of synaptic plasticity require rapid, local activation of protein synthesis. Although this is thought to reflect recruitment of mRNAs to free ribosomes, this would limit the speed and magnitude of translational activation. Here we provide compelling in situ evidence supporting an alternative model in which synaptic mRNAs are transported as stably paused polyribosomes. Remarkably, we show that metabotropic glutamate receptor activation allows the synthesis of proteins that lead to a functional long-term depression phenotype even when translation initiation has been greatly reduced. Thus, neurons evolved a unique mechanism to swiftly translate synaptic mRNAs into functional protein upon synaptic signaling using stalled polyribosomes to bypass the rate-limiting step of translation initiation. Because dysregulated plasticity is implicated in neurodevelopmental and psychiatric disorders such as fragile X syndrome, this work uncovers a unique translational target for therapies. PMID:24043809

Integrative application of active controls (IAAC) technology to an advanced subsonic transport project. Initial act configuration design study

NASA Technical Reports Server (NTRS)

1980-01-01

The performance and economic benefits of a constrained application of Active Controls Technology (ACT) are identified, and the approach to airplane design is established for subsequent steps leading to the development of a less constrained final ACT configuration. The active controls configurations are measured against a conventional baseline configuration, a state-of-the-art transport, to determine whether the performance and economic changes resulting from ACT merit proceeding with the project. The technology established by the conventional baseline configuration was held constant except for the addition of ACT. The wing, with the same planform, was moved forward on the initial ACT configuration to move the loading range aft relative to the wing mean aerodynamic chord. Wing trailing-edge surfaces and surface controls also were reconfigured for load alleviation and structural stabilization.

Control of mediolateral stability during rapid step initiation with preferred and non-preferred leg: is it symmetrical?

PubMed

Yiou, E; Do, M C

2010-05-01

During voluntary stepping initiation, postural stability along the mediolateral direction is controlled via "anticipatory postural adjustment" (APA). This study tested the hypothesis that, in young healthy subjects, the biomechanical features of mediolateral APA depend on the leg that initiates stepping. Subjects (N=10) initiated a rapid single step with the preferred (P condition) and the non-preferred leg (NP condition) on a force-plate. Results showed that mediolateral APA duration (P=0.020) and amplitude were higher (as attested by the increase in maximal center-of-gravity velocity (P=0.003) and displacement (P<0.001) during APA), and that mediolateral stability was better (as attested by the attenuation in center-of-gravity velocity at time of swing-foot contact (P=0.007)) in P than in NP. These results support the view that stepping initiation in healthy subjects involves postural asymmetry. This statement may have relevant implications in clinical evaluation where postural asymmetry is generally considered as reflecting postural impairment. Copyright 2010 Elsevier B.V. All rights reserved.

Hydrophobic Shielding Drives Catalysis of Hydride Transfer in a Family of F420H2-Dependent Enzymes.

PubMed

Mohamed, A Elaaf; Condic-Jurkic, Karmen; Ahmed, F Hafna; Yuan, Peng; O'Mara, Megan L; Jackson, Colin J; Coote, Michelle L

2016-12-13

A family of flavin/deazaflavin-dependent oxidoreductases (FDORs) from mycobacteria has been recently characterized and found to play a variety of catalytic roles, including the activation of prodrugs such as the candidate anti-tuberculosis drug pretomanid (PA-824). However, our understanding of the catalytic mechanism used by these enzymes is relatively limited. To address this, we have used a combination of quantum mechanics and molecular dynamics calculations to study the catalytic mechanism of the activation of pretomanid by the deazaflavin-dependent nitroreductase (Ddn) from Mycobacterium tuberculosis. The preferred pathway involves an initial hydride transfer step from the deprotonated cofactor (i.e., F 420 H - ), with subsequent protonation, before a series of spontaneous intramolecular reactions to form the final reactive nitrogen species. The most likely proton source is a hydroxonium ion within the solvent accessible active site. Intriguingly, catalysis of the rate-determining hydride transfer step is aided by three tyrosine residues that form a hydrophobic barrier around the active site that, upon reaction, is then disrupted to allow increased water accessibility to facilitate the subsequent proton transfer step. The catalytic mechanism we propose is consistent with previous experimental observations of the Ddn enzyme and will inform the design of improved prodrugs in the future.

[Characterization of structural change of ascorbate peroxidase from Chinese kale during denaturation by circular dichroism].

PubMed

Xi, Jia-Fu; Tang, Lei; Zhang, Jian-Hua; Zhang, Hong-Jian; Chen, Xu-Sheng; Mao, Zhong-Gui

2014-11-01

Circular dichroism (CD) is a special absorption spectrum. The secondary structure of protein such as α-helix, β-sheet and β-turn in the far ultraviolet region (190-250 nm) has a characteristic CD spectrum. In order to understand the activity and structural changes of ascorbate peroxidase from Chinese kale (BaAPX) during denaturation, specific activity and percentage of secondary structure of BaAPX under different time, temperature and concentration were analyzed by CD dynamically. In addition, the percentage of four secondary structures in BaAPX was calculated by CD analysis software Dichroweb. The results show that BaAPX is a full α-type enzyme whose specific activity is positively related to the percentage of α-helix. During denaturation of BaAPX, three kinds of structural changes were proposed: the one-step structural change from initial state (N state) to minimum state of α-helix (R state) under low concentration and low temperature; the one-step structural change from N state to equilibrium state (T state) under high concentration and low temperature; the two-step structural changes from N state through R state to final T state under heat treatment and low temperature renaturation.

Taking Leadership in Initiating a Comprehensive US International Education Policy

ERIC Educational Resources Information Center

Lad, Kaetlyn

2008-01-01

A first step to ensuring that emerging school leaders possess the dispositions and skills necessary to be successful in a global community is for educational leaders to take initiative in moving toward a comprehensive Us International Education Policy. This article introduces possible steps to initiate such a policy.

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

Ahn, Cheol Hyoun; Hee Kim, So; Gu Yun, Myeong

In this study, we proposed the artificially designed channel structure in oxide thin-film transistors (TFTs) called a “step-composition gradient channel.” We demonstrated Al step-composition gradient Al-Zn-O (AZO) channel structures consisting of three AZO layers with different Al contents. The effects of stacking sequence in the step-composition gradient channel on performance and electrical stability of bottom-gate TFT devices were investigated with two channels of inverse stacking order (ascending/descending step-composition). The TFT with ascending step-composition channel structure (5 → 10 → 14 at. % Al composition) showed relatively negative threshold voltage (−3.7 V) and good instability characteristics with a reduced threshold voltage shift (Δmore » 1.4 V), which was related to the alignment of the conduction band off-set within the channel layer depending on the Al contents. Finally, the reduced Al composition in the initial layer of ascending step-composition channel resulted in the best field effect mobility of 4.5 cm{sup 2}/V s. We presented a unique active layer of the “step-composition gradient channel” in the oxide TFTs and explained the mechanism of adequate channel design.« less

Development and Validation of Web-Based Question Bank and Evaluation of Its Utility among Students and Teachers

ERIC Educational Resources Information Center

Parthasarathy, M.; Ananthasayanam, R.

2016-01-01

Rushing efforts are taken by developing and under-developed countries to match educational standards of developed countries. Education is a life-long activity and continuing process for which necessary steps are initiated to offer and gain with minimum cost of resources. Creating Open Educational Resources (OER) is the preferably right choice in…

The Person and the Planet: A Problems Course. A Curriculum Guide. Revised Edition.

ERIC Educational Resources Information Center

Widutis, Florence

Growth occurs when the need for change is recognized by the individual through self-analysis, and when measures to effect the change are self-initiated. In this course the student is actively involved at every step in self-evaluation, identifying problem areas in her or his relationships and environment, selecting topics and issues for research,…

Making a Difference: TPSR, a New Wave of Youth Development Changing Lives One Stroke at a Time

ERIC Educational Resources Information Center

Beale, Angela

2016-01-01

This article was inspired by a belief in the need to connect physical education with community-based physical activity programming in minority communities. The initial steps of this reflective narrative were described in a previous article. This article describes a program called Project Guard: Make A Splash E.N.D. (End Needless Drowning), a…

Late Maturation Steps Preceding Selective Nuclear Export and Egress of Progeny Parvovirus

PubMed Central

Wolfisberg, Raphael; Kempf, Christoph

2016-01-01

ABSTRACT Although the mechanism is not well understood, growing evidence indicates that the nonenveloped parvovirus minute virus of mice (MVM) may actively egress before passive release through cell lysis. We have dissected the late maturation steps of the intranuclear progeny with the aims of confirming the existence of active prelytic egress and identifying critical capsid rearrangements required to initiate the process. By performing anion-exchange chromatography (AEX), we separated intranuclear progeny particles by their net surface charges. Apart from empty capsids (EC), two distinct populations of full capsids (FC) arose in the nuclei of infected cells. The earliest population of FC to appear was infectious but, like EC, could not be actively exported from the nucleus. Further maturation of this early population, involving the phosphorylation of surface residues, gave rise to a second, late population with nuclear export potential. While capsid surface phosphorylation was strictly associated with nuclear export capacity, mutational analysis revealed that the phosphoserine-rich N terminus of VP2 (N-VP2) was dispensable, although it contributed to passive release. The reverse situation was observed for the incoming particles, which were dephosphorylated in the endosomes. Our results confirm the existence of active prelytic egress and reveal a late phosphorylation event occurring in the nucleus as a selective factor for initiating the process. IMPORTANCE In general, the process of egress of enveloped viruses is active and involves host cell membranes. However, the release of nonenveloped viruses seems to rely more on cell lysis. At least for some nonenveloped viruses, an active process before passive release by cell lysis has been reported, although the underlying mechanism remains poorly understood. By using the nonenveloped model parvovirus minute virus of mice, we could confirm the existence of an active process of nuclear export and further characterize the associated capsid maturation steps. Following DNA packaging in the nucleus, capsids required further modifications, involving the phosphorylation of surface residues, to acquire nuclear export potential. Inversely, those surface residues were dephosphorylated on entering capsids. These spatially controlled phosphorylation-dephosphorylation events concurred with the nuclear export-import potential required to complete the infectious cycle. PMID:27009963

Late Maturation Steps Preceding Selective Nuclear Export and Egress of Progeny Parvovirus.

PubMed

Wolfisberg, Raphael; Kempf, Christoph; Ros, Carlos

2016-06-01

Although the mechanism is not well understood, growing evidence indicates that the nonenveloped parvovirus minute virus of mice (MVM) may actively egress before passive release through cell lysis. We have dissected the late maturation steps of the intranuclear progeny with the aims of confirming the existence of active prelytic egress and identifying critical capsid rearrangements required to initiate the process. By performing anion-exchange chromatography (AEX), we separated intranuclear progeny particles by their net surface charges. Apart from empty capsids (EC), two distinct populations of full capsids (FC) arose in the nuclei of infected cells. The earliest population of FC to appear was infectious but, like EC, could not be actively exported from the nucleus. Further maturation of this early population, involving the phosphorylation of surface residues, gave rise to a second, late population with nuclear export potential. While capsid surface phosphorylation was strictly associated with nuclear export capacity, mutational analysis revealed that the phosphoserine-rich N terminus of VP2 (N-VP2) was dispensable, although it contributed to passive release. The reverse situation was observed for the incoming particles, which were dephosphorylated in the endosomes. Our results confirm the existence of active prelytic egress and reveal a late phosphorylation event occurring in the nucleus as a selective factor for initiating the process. In general, the process of egress of enveloped viruses is active and involves host cell membranes. However, the release of nonenveloped viruses seems to rely more on cell lysis. At least for some nonenveloped viruses, an active process before passive release by cell lysis has been reported, although the underlying mechanism remains poorly understood. By using the nonenveloped model parvovirus minute virus of mice, we could confirm the existence of an active process of nuclear export and further characterize the associated capsid maturation steps. Following DNA packaging in the nucleus, capsids required further modifications, involving the phosphorylation of surface residues, to acquire nuclear export potential. Inversely, those surface residues were dephosphorylated on entering capsids. These spatially controlled phosphorylation-dephosphorylation events concurred with the nuclear export-import potential required to complete the infectious cycle. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Continuous track paths reveal additive evidence integration in multistep decision making.

PubMed

Buc Calderon, Cristian; Dewulf, Myrtille; Gevers, Wim; Verguts, Tom

2017-10-03

Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.

Intervention-related increases in preoperative physical activity are maintained 6-months after Bariatric surgery: results from the bari-active trial.

PubMed

Bond, D S; Thomas, J G; Vithiananthan, S; Unick, J; Webster, J; Roye, G D; Ryder, B A; Sax, H C

2017-03-01

Higher preoperative physical activity (PA) strongly predicts higher post-operative PA in bariatric surgery (BS) patients, providing rationale for preoperative PA interventions (PAIs). However, whether PAI-related increases can be maintained post-operatively has not been examined. This study compared PA changes across pre- (baseline, post-intervention) and post-operative (6-month follow up) periods in participants randomized to 6 weeks of preoperative PAI or standard care control (SC). Of 75 participants initially randomized, 36 (PAI n=22; SC n=14) underwent BS. Changes in daily bout-related (⩾10-min bouts) moderate-to-vigorous PA (MVPA) and steps were assessed via the SenseWear Armband monitor. PAI received weekly counseling to increase walking exercise. Retention (86%) at post-operative follow up was similar between groups. Intent-to-treat analyses showed that PAI vs SC had greater increases across time (baseline, post-intervention, follow up) in bout-related MVPA minutes/day (4.3±5.1, 26.3±21.3, 28.7±26.3 vs 10.4±22.9, 11.4±16.0, 18.5±28.2; P=0.013) and steps/day (5163±2901, 7950±3286, 7870±3936 vs 5163±2901, 5601±3368, 5087±2603; P<0.001). PAI differed from SC on bout-related MVPA at post-intervention (P=0.016; d=0.91), but not follow up (P=0.15; d=0.41), and steps at post-intervention (P=0.031; d=0.78) and follow up (P=0.024; d=0.84). PAI participants maintained preoperative PA increases post-operatively. Findings support preoperative PAIs and research to test whether PA changes can be sustained and influence surgical outcomes beyond the initial post-operative period.

Initiation precursors and initiators in laser-induced copolymerization of styrene and maleic anhydride in acetone

NASA Technical Reports Server (NTRS)

Miner, Gilda A.; Meador, Willard E.; Chang, C. Ken

1990-01-01

The initiation step of photopolymerized styrene/maleic anhydride copolymer was investigated at 365 nm. UV absorption measurements provide decisive evidence that the styrene/maleic anhydride charge transfer complex is the sole absorbing species; however, key laser experiments suggest intermediate reactions lead to a monoradical initiating species. A mechanism for the photoinitiation step of the copolymer is proposed.

Automatic Rooftop Extraction in Stereo Imagery Using Distance and Building Shape Regularized Level Set Evolution

NASA Astrophysics Data System (ADS)

Tian, J.; Krauß, T.; d'Angelo, P.

2017-05-01

Automatic rooftop extraction is one of the most challenging problems in remote sensing image analysis. Classical 2D image processing techniques are expensive due to the high amount of features required to locate buildings. This problem can be avoided when 3D information is available. In this paper, we show how to fuse the spectral and height information of stereo imagery to achieve an efficient and robust rooftop extraction. In the first step, the digital terrain model (DTM) and in turn the normalized digital surface model (nDSM) is generated by using a newly step-edge approach. In the second step, the initial building locations and rooftop boundaries are derived by removing the low-level pixels and high-level pixels with higher probability to be trees and shadows. This boundary is then served as the initial level set function, which is further refined to fit the best possible boundaries through distance regularized level-set curve evolution. During the fitting procedure, the edge-based active contour model is adopted and implemented by using the edges indicators extracted from panchromatic image. The performance of the proposed approach is tested by using the WorldView-2 satellite data captured over Munich.

[Differences in anticipatory postural adjustments between self-generated and triggered gait initiation in 20 healthy subjects].

PubMed

Delval, A; Krystkowiak, P; Blatt, J-L; Labyt, E; Destée, A; Derambure, P; Defebvre, L

2005-01-01

Preparation of upper-limb movements differs between self-paced and triggered conditions. This study analyzed the anticipatory postural adjustments (APAs) of gait initiation in normal subjects in 2 conditions: self-generated and triggered by a "beep" sound. We recorded kinematic, spatiotemporal parameters of the first two steps by means of video motion analysis (6 infrared cameras), and kinetic parameters (using a force platform and the optoelectronic system) in 20 normal subjects. Two conditions: 1) self-generated initiation; and 2) initiation triggered by a "beep" sound were studied to evaluate the APA phase, by recording kinetic data (duration of the APAs, trajectory of the center of pressure, speed and trajectory of the center of mass). Kinematic data (first and second step speed, length and duration) were also recorded. First step speed and length were increased in self-paced gait initiation compared to triggered gait initiation in controls. We found no difference between the 2 conditions in terms of second step kinematic data. It was caused by a significant difference between the 2 conditions for the temporal characteristics of anticipatory postural adjustments (APAs) in the initiation of the first step, which was longer when normal subjects performed self-generated gait initiation. The trajectory of center of pressure and center of mass remained the same in the 2 conditions. APAs of gait initiation process are delayed under self-paced condition, although they do not differ qualitatively between reaction time and self-paced condition. Neuphysiological support of self-generated movement could explain these differences.

Carotenoid content of the varieties Jaranda and Jariza (Capsicumannuum L.) and response during the industrial slow drying and grinding steps in paprika processing.

PubMed

Mínguez-Mosquera, M I; Pérez-Gálvez, A; Garrido-Fernández, J

2000-07-01

Fruits of the pepper varieties Jaranda and Jariza (Capsicum annuum L. ) ripen as a group, enabling a single harvesting, showed a uniform carotenoid content that is high enough (7.9 g/kg) for the production of paprika. The drying system at mild temperature showed that fruits with moisture content of 85-88% generated a dry product with carotenoid content equal to or higher than the initial one. Those high moisture levels allowed the fruits to have a longer period of metabolic activity, increasing the yellow fraction, the red fraction, or both as a function of what biosynthetic process was predominant. This fact indicates under-ripeness of the fruits in the drying step. The results obtained allow us to establish that both varieties, Jaranda and Jariza, fit the dehydration process employed, yielding a dry fruit with carotenoid concentration similar to that the initial one. During the grinding step of the dry fruit, the heat generated by the hammers of the mill caused degradation of the yellow fraction, while the red fraction is maintained. The ripeness state of the harvested fruits and the appropriateness or severity of the processing steps are indicated by the ratio of red to yellow (R/Y) and/or red to total (R/T) pigments, since fluctuations in both fractions and in total pigments are reflected in and monitored by these parameters.

Are Active Australia physical activity questions valid for older adults?

PubMed

Heesch, Kristiann C; Hill, Robert L; van Uffelen, Jannique G Z; Brown, Wendy J

2011-05-01

The Active Australia Survey (AAS) is used for physical activity (PA) surveillance in the general Australian adult population, but its validity in older adults has not been evaluated. Our aim was to examine the convergent validity of the AAS questions in older adults. The AAS was validated against pedometer step counts as an objective measure of PA, self-reported physical function, and a step-test to assess cardiorespiratory fitness. Participants were community-dwelling adults, aged 65-89 y, with the ability to walk 100 m. They completed a self-administered AAS and the step-test in one interview. One week earlier, they completed the Short Form-36 physical function subscale. Between these two interviews, they each wore a YAMAX Digiwalker SW200 pedometer and recorded daily steps. Using the AAS data, daily walking minutes and total PA minutes (walking, moderate-intensity PA and vigorous-intensity PA) were compared with the validity measures using Spearman rank-order correlations. Fifty-three adults completed the study. Median daily walking minutes were 34.2 (interquartile range [IQR] 17.1, 60.0), and median daily total PA minutes were 68.6 (IQR 31.4, 113.6). Walking and total PA minutes were both moderately correlated with pedometer steps (Spearman correlation r=0.42, p=0.003, for each) but not with step-test seconds to completion (r=-0.11, p=0.44; r=-0.25, p=0.08, respectively). Total PA minutes were significantly correlated with physical function scores (r=0.39, p=0.004), but walking minutes were not (r=0.15, p=0.29). This initial examination of the psychometric properties of the AAS for older adults suggests that this surveillance tool has acceptable convergent validity for ambulatory, community-dwelling older adults. Copyright © 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Back off! The effect of emotion on backward step initiation.

PubMed

Bouman, Daniëlle; Stins, John F

2018-02-01

The distance regulation (DR) hypothesis states that actors are inclined to increase their distance from an unpleasant stimulus. The current study investigated the relation between emotion and its effect on the control of backward step initiation, which constitutes an avoidance-like behavior. Participants stepped backward on a force plate in response to neutral, high-arousing pleasant and high-arousing unpleasant visual emotional stimuli. Gait initiation parameters and the results of an exploratory analysis of postural sway were compared across the emotion categories using significance testing and Bayesian statistics. Evidence was found that gait initiation parameters were largely unaffected by emotional conditions. In contrast, the exploratory analysis of postural immobility showed a significant effect: highly arousing stimuli (pleasant and unpleasant) resulted in more postural sway immediately preceding gait initiation compared to neutral stimuli. This suggests that arousal, rather than valence, affects pre-step sway. These results contradict the DR hypothesis, since avoidance gait-initiation in response to unpleasant stimuli was no different compared to pleasant stimuli. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Immobilization of glucose oxidase into polyaniline nanofiber matrix for biofuel cell applications.

PubMed

Kim, Hyeongseok; Lee, Inseon; Kwon, Yongchai; Kim, Byoung Chan; Ha, Su; Lee, Jung-heon; Kim, Jungbae

2011-05-15

Glucose oxidase (GOx) was immobilized into the porous matrix of polyaniline nanofibers in a three-step process, consisting of enzyme adsorption, precipitation, and crosslinking (EAPC). EAPC was highly active and stable when compared to the control samples of enzyme adsorption (EA) and enzyme adsorption and crosslinking (EAC) with no step of enzyme precipitation. The GOx activity of EAPC was 9.6 and 4.2 times higher than those of EA and EAC, respectively. Under rigorous shaking at room temperature for 56 days, the relative activities of EA, EAC and EAPC, defined as the percentage of residual activity to the initial activity, were 22%, 19% and 91%, respectively. When incubated at 50°C under shaking for 4h, EAPC showed a negligible decrease of GOx activity while the relative activities of EA and EAC were 45% and 48%, respectively. To demonstrate the feasible application of EAPC in biofuel cells, the enzyme anodes were prepared and used for home-built air-breathing biofuel cells. The maximum power densities of biofuel cells with EA and EAPC anodes were 57 and 292 μW/cm(2), respectively. After thermal treatment at 60°C for 4h, the maximum power density of EA and EAPC anodes were 32 and 315 μW/cm(2), representing 56% and 108% of initially obtained maximum power densities, respectively. Because the lower power densities and short lifetime of biofuel cells are serious problems against their practical applications, the present results with EAPC anode has opened up a new potential for the realization of practical biofuel cell applications. Copyright © 2011 Elsevier B.V. All rights reserved.

Aging effect on step adjustments and stability control in visually perturbed gait initiation.

PubMed

Sun, Ruopeng; Cui, Chuyi; Shea, John B

2017-10-01

Gait adaptability is essential for fall avoidance during locomotion. It requires the ability to rapidly inhibit original motor planning, select and execute alternative motor commands, while also maintaining the stability of locomotion. This study investigated the aging effect on gait adaptability and dynamic stability control during a visually perturbed gait initiation task. A novel approach was used such that the anticipatory postural adjustment (APA) during gait initiation were used to trigger the unpredictable relocation of a foot-size stepping target. Participants (10 young adults and 10 older adults) completed visually perturbed gait initiation in three adjustment timing conditions (early, intermediate, late; all extracted from the stereotypical APA pattern) and two adjustment direction conditions (medial, lateral). Stepping accuracy, foot rotation at landing, and Margin of Dynamic Stability (MDS) were analyzed and compared across test conditions and groups using a linear mixed model. Stepping accuracy decreased as a function of adjustment timing as well as stepping direction, with older subjects exhibited a significantly greater undershoot in foot placement to late lateral stepping. Late adjustment also elicited a reaching-like movement (i.e. foot rotation prior to landing in order to step on the target), regardless of stepping direction. MDS measures in the medial-lateral and anterior-posterior direction revealed both young and older adults exhibited reduced stability in the adjustment step and subsequent steps. However, young adults returned to stable gait faster than older adults. These findings could be useful for future study of screening deficits in gait adaptability and preventing falls. Copyright © 2017 Elsevier B.V. All rights reserved.

Falls-risk post-stroke: Examining contributions from paretic versus non paretic limbs to unexpected forward gait slips.

PubMed

Kajrolkar, Tejal; Bhatt, Tanvi

2016-09-06

Community-dwelling stroke survivors show a high incidence of falls with unexpected external perturbations during dynamic activities like walking. Previous evidence has demonstrated the importance of compensatory stepping to restore dynamic stability in response to perturbations in hemiparetic stroke survivors. However, these studies were limited to either stance perturbations or perturbation induced under the unaffected limb. This study aimed to compare the differences, if any, between the non-paretic and paretic sides in dynamic stability and protective stepping strategies when exposed to unexpected external perturbation during walking. Twenty hemiparetic subjects experienced an unexpected forward slip during walking on the laboratory walkway either on the paretic (n=10) or the nonparetic limb (n=10). Both groups demonstrated a backward loss of balance with a compensatory stepping response, with the nonparetic-side slip group resorting mainly to an aborted step response (60%) and the paretic-side slip group mainly exhibiting a recovery step response (90%). Although both groups showed an equal incidence of falls, the nonparetic-side slip group demonstrated a higher stability at recovery step touchdown, resulting from lower perturbation magnitudes (slip displacement and velocity) compared to the paretic-side slip group. The results indicate that the paretic side had difficulty initiating and executing a successful stepping response (nonparetic-side slip) and also in reactive limb control while in stance (paretic-side slip). Based on these results it is suggested that intervention strategies for fall-prevention in chronic stroke survivors should focus on paretic limb training for both reactive stepping and weight bearing for improving balance control for recovery from unpredictable perturbations during dynamic activities such as walking. Copyright © 2016. Published by Elsevier Ltd.

Assessment of a Mobile Game ("MobileKids Monster Manor") to Promote Physical Activity Among Children.

PubMed

Garde, Ainara; Umedaly, Aryannah; Abulnaga, S Mazdak; Robertson, Leah; Junker, Anne; Chanoine, Jean Pierre; Ansermino, J Mark; Dumont, Guy A

2015-04-01

The majority of children in North America are not meeting current physical activity guidelines. The purpose of this study was to evaluate the impact of a mobile phone game ("MobileKids Monster Manor") as a tool to promote voluntary physical activity among children. The game integrates data from an accelerometer-based activity monitor (Tractivity(®); Kineteks Corp., Vancouver, BC, Canada) wirelessly connected to a phone and was developed with the involvement of a team of young advisors (KidsCan Initiative: Involving Youth as Ambassadors for Research). Fifty-four children 8-13 years old completed a week of baseline data collection by wearing an accelerometer but receiving no feedback about their activity levels. The 54 children were then sequentially assigned to two groups: One group played "MobileKids Monster Manor," and the other received daily activity feedback (steps and active minutes) via an online program. The physical activity (baseline and intervention weeks) was measured using the activity monitor and compared using two-way repeated-measures analysis of variance (intervention×time). Forty-seven children with a body mass index (BMI) z-score of 0.35±1.18 successfully completed the study. Significant (P=0.01) increases in physical activity were observed during the intervention week in both the game and feedback groups (1191 and 796 steps/day, respectively). In the game group, greater physical activity was demonstrated in children with higher BMI z-score, showing 964 steps/day more per BMI z-score unit (P=0.03; 95 percent confidence interval of 98 to 1829). Further investigation is required to confirm that our game design promotes physical activity.

A Unified Model of Cloud-to-Ground Lightning Stroke

NASA Astrophysics Data System (ADS)

Nag, A.; Rakov, V. A.

2014-12-01

The first stroke in a cloud-to-ground lightning discharge is thought to follow (or be initiated by) the preliminary breakdown process which often produces a train of relatively large microsecond-scale electric field pulses. This process is poorly understood and rarely modeled. Each lightning stroke is composed of a downward leader process and an upward return-stroke process, which are usually modeled separately. We present a unified engineering model for computing the electric field produced by a sequence of preliminary breakdown, stepped leader, and return stroke processes, serving to transport negative charge to ground. We assume that a negatively-charged channel extends downward in a stepped fashion through the relatively-high-field region between the main negative and lower positive charge centers and then through the relatively-low-field region below the lower positive charge center. A relatively-high-field region is also assumed to exist near ground. The preliminary breakdown pulse train is assumed to be generated when the negatively-charged channel interacts with the lower positive charge region. At each step, an equivalent current source is activated at the lower extremity of the channel, resulting in a step current wave that propagates upward along the channel. The leader deposits net negative charge onto the channel. Once the stepped leader attaches to ground (upward connecting leader is presently neglected), an upward-propagating return stroke is initiated, which neutralizes the charge deposited by the leader along the channel. We examine the effect of various model parameters, such as step length and current propagation speed, on model-predicted electric fields. We also compare the computed fields with pertinent measurements available in the literature.

Pausing and activating thread state upon pin assertion by external logic monitoring polling loop exit time condition

DOEpatents

Chen, Dong; Giampapa, Mark; Heidelberger, Philip; Ohmacht, Martin; Satterfield, David L; Steinmacher-Burow, Burkhard; Sugavanam, Krishnan

2013-05-21

A system and method for enhancing performance of a computer which includes a computer system including a data storage device. The computer system includes a program stored in the data storage device and steps of the program are executed by a processer. The processor processes instructions from the program. A wait state in the processor waits for receiving specified data. A thread in the processor has a pause state wherein the processor waits for specified data. A pin in the processor initiates a return to an active state from the pause state for the thread. A logic circuit is external to the processor, and the logic circuit is configured to detect a specified condition. The pin initiates a return to the active state of the thread when the specified condition is detected using the logic circuit.

ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.

PubMed

Parke, Courtney L; Wojcik, Edward J; Kim, Sunyoung; Worthylake, David K

2010-02-19

Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.

ANTICIPATORY POSTURAL ADJUSTMENTS PRIOR TO STEP INITIATION ARE HYPOMETRIC IN UNTREATED PARKINSON'S DISEASE: AN ACCELEROMETER-BASED APPROACH

PubMed Central

Mancini, Martina; Zampieri, Cris; Carlson-Kuhta, Patricia; Chiari, Lorenzo; Horak, Fay B.

2010-01-01

Background and purpose Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson's disease (PD) and may be one of the factors associated with ‘start hesitation’. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. Methods Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). Results Our findings show that APAs measured from the peak COP displacement towards the swing leg and the peak trunk acceleration towards the stance leg were smaller in untreated PD compared to control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. Conclusion These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes. PMID:19473350

Proton pump inhibitor step-down therapy for GERD: A multi-center study in Japan

PubMed Central

Tsuzuki, Takao; Okada, Hiroyuki; Kawahara, Yoshiro; Takenaka, Ryuta; Nasu, Junichiro; Ishioka, Hidehiko; Fujiwara, Akiko; Yoshinaga, Fumiya; Yamamoto, Kazuhide

2011-01-01

AIM: To investigate the predictors of success in step-down of proton pump inhibitor and to assess the quality of life (QOL). METHODS: Patients who had heartburn twice a week or more were treated with 20 mg omeprazole (OPZ) once daily for 8 wk as an initial therapy (study 1). Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo (study 2). QOL was investigated using the gastrointestinal symptom rating scale (GSRS) before initial therapy, after both 4 and 8 wk of initial therapy, and at 1, 2, 3, and 6 mo after starting maintenance therapy. RESULTS: In study 1, 108 patients were analyzed. Their characteristics were as follows; median age: 63 (range: 20-88) years, sex: 46 women and 62 men. The success rate of the initial therapy was 76%. In the patients with successful initial therapy, abdominal pain, indigestion and reflux GSRS scores were improved. In study 2, 83 patients were analyzed. Seventy of 83 patients completed the study 2 protocol. In the per-protocol analysis, 80% of 70 patients were successful for step-down. On multivariate analysis of baseline demographic data and clinical information, no previous treatment for gastroesophageal reflux disease (GERD) [odds ratio (OR) 0.255, 95% CI: 0.06-0.98] and a lower indigestion score in GSRS at the beginning of step-down therapy (OR 0.214, 95% CI: 0.06-0.73) were found to be the predictors of successful step-down therapy. The improved GSRS scores by initial therapy were maintained through the step-down therapy. CONCLUSION: OPZ was effective for most GERD patients. However, those who have had previous treatment for GERD and experience dyspepsia before step-down require particular monitoring for relapse. PMID:21472108

Does a microprocessor-controlled prosthetic knee affect stair ascent strategies in persons with transfemoral amputation?

PubMed

Aldridge Whitehead, Jennifer M; Wolf, Erik J; Scoville, Charles R; Wilken, Jason M

2014-10-01

Stair ascent can be difficult for individuals with transfemoral amputation because of the loss of knee function. Most individuals with transfemoral amputation use either a step-to-step (nonreciprocal, advancing one stair at a time) or skip-step strategy (nonreciprocal, advancing two stairs at a time), rather than a step-over-step (reciprocal) strategy, because step-to-step and skip-step allow the leading intact limb to do the majority of work. A new microprocessor-controlled knee (Ottobock X2(®)) uses flexion/extension resistance to allow step-over-step stair ascent. We compared self-selected stair ascent strategies between conventional and X2(®) prosthetic knees, examined between-limb differences, and differentiated stair ascent mechanics between X2(®) users and individuals without amputation. We also determined which factors are associated with differences in knee position during initial contact and swing within X2(®) users. Fourteen individuals with transfemoral amputation participated in stair ascent sessions while using conventional and X2(®) knees. Ten individuals without amputation also completed a stair ascent session. Lower-extremity stair ascent joint angles, moment, and powers and ground reaction forces were calculated using inverse dynamics during self-selected strategy and cadence and controlled cadence using a step-over-step strategy. One individual with amputation self-selected a step-over-step strategy while using a conventional knee, while 10 individuals self-selected a step-over-step strategy while using X2(®) knees. Individuals with amputation used greater prosthetic knee flexion during initial contact (32.5°, p = 0.003) and swing (68.2°, p = 0.001) with higher intersubject variability while using X2(®) knees compared to conventional knees (initial contact: 1.6°, swing: 6.2°). The increased prosthetic knee flexion while using X2(®) knees normalized knee kinematics to individuals without amputation during swing (88.4°, p = 0.179) but not during initial contact (65.7°, p = 0.002). Prosthetic knee flexion during initial contact and swing were positively correlated with prosthetic limb hip power during pull-up (r = 0.641, p = 0.046) and push-up/early swing (r = 0.993, p < 0.001), respectively. Participants with transfemoral amputation were more likely to self-select a step-over-step strategy similar to individuals without amputation while using X2(®) knees than conventional prostheses. Additionally, the increased prosthetic knee flexion used with X2(®) knees placed large power demands on the hip during pull-up and push-up/early swing. A modified strategy that uses less knee flexion can be used to allow step-over-step ascent in individuals with less hip strength.

Emerging Therapeutics Targeting mRNA Translation

PubMed Central

Malina, Abba; Mills, John R.; Pelletier, Jerry

2012-01-01

A defining feature of many cancers is deregulated translational control. Typically, this occurs at the level of recruitment of the 40S ribosomes to the 5′-cap of cellular messenger RNAs (mRNAs), the rate-limiting step of protein synthesis, which is controlled by the heterotrimeric eukaryotic initiation complex eIF4F. Thus, eIF4F in particular, and translation initiation in general, represent an exploitable vulnerability and unique opportunity for therapeutic intervention in many transformed cells. In this article, we discuss the development, mode of action and biological activity of a number of small-molecule inhibitors that interrupt PI3K/mTOR signaling control of eIF4F assembly, as well as compounds that more directly block eIF4F activity. PMID:22474009

Hippuristanol - A potent steroid inhibitor of eukaryotic initiation factor 4A

PubMed Central

Cencic, Regina; Pelletier, Jerry

2016-01-01

ABSTRACT Protein synthesis and its regulatory signaling pathways play essential roles in the initiation and maintenance of the cancer phenotype. Insight obtained over the last 3 decades on the mechanisms regulating translation in normal and transformed cells have revealed that perturbed control in cancer cells may offer an Achilles' heel for the development of novel anti-neoplastic agents. Several small molecule inhibitors have been identified and characterized that target translation initiation – more specifically, the rate-limiting step where ribosomes are recruited to mRNA templates. Among these, hippuristanol, a polyhydroxysteroid from the gorgonian Isis hippuris has been found to inhibit translation initiation by blocking the activity of eukaryotic initiation factor (eIF) 4A, an essential RNA helicase involved in this process. Herein, we highlight the biological properties of this compound, its potential development as an anti-cancer agent, and its use to validate eIF4A as an anti-neoplastic target. PMID:27335721

Engaging with Quality Improvement Initiatives: A Descriptive Study of Learning in the Complex and Dynamic Context of Everyday Life for Family Child Care Providers

ERIC Educational Resources Information Center

Tonyan, Holli A.; Nuttall, Joce; Torres, Jeannette; Bridgewater, Jessie

2017-01-01

Research Findings: This article reports on family child care providers' views about their engagement with professional development programs, including providers who were and were not participating in Quality Rating and Improvement Systems in Los Angeles, California. Most providers participating in the study were taking active steps to improve…

One-step synthesis of high-yield biodiesel from waste cooking oils by a novel and highly methanol-tolerant immobilized lipase.

PubMed

Wang, Xiumei; Qin, Xiaoli; Li, Daoming; Yang, Bo; Wang, Yonghua

2017-07-01

This study reported a novel immobilized MAS1 lipase from marine Streptomyces sp. strain W007 for synthesizing high-yield biodiesel from waste cooking oils (WCO) with one-step addition of methanol in a solvent-free system. Immobilized MAS1 lipase was selected for the transesterification reactions with one-step addition of methanol due to its much more higher biodiesel yield (89.50%) when compared with the other three commercial immobilized lipases (<10%). The highest biodiesel yield (95.45%) was acquired with one-step addition of methanol under the optimized conditions. Moreover, it was observed that immobilized MAS1 lipase retained approximately 70% of its initial activity after being used for four batch cycles. Finally, the obtained biodiesel was further characterized using FT-IR, 1 H and 13 C NMR spectroscopy. These findings indicated that immobilized MAS1 lipase is a promising catalyst for biodiesel production from WCO with one-step addition of methanol under high methanol concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Generation of highly purified neural stem cells from human adipose-derived mesenchymal stem cells by Sox1 activation.

PubMed

Feng, Nianhua; Han, Qin; Li, Jing; Wang, Shihua; Li, Hongling; Yao, Xinglei; Zhao, Robert Chunhua

2014-03-01

Neural stem cells (NSCs) are ideal candidates in stem cell-based therapy for neurodegenerative diseases. However, it is unfeasible to get enough quantity of NSCs for clinical application. Generation of NSCs from human adipose-derived mesenchymal stem cells (hAD-MSCs) will provide a solution to this problem. Currently, the differentiation of hAD-MSCs into highly purified NSCs with biological functions is rarely reported. In our study, we established a three-step NSC-inducing protocol, in which hAD-MSCs were induced to generate NSCs with high purity after sequentially cultured in the pre-inducing medium (Step1), the N2B27 medium (Step2), and the N2B27 medium supplement with basic fibroblast growth factor and epidermal growth factor (Step3). These hAD-MSC-derived NSCs (adNSCs) can form neurospheres and highly express Sox1, Pax6, Nestin, and Vimentin; the proportion was 96.1% ± 1.3%, 96.8% ± 1.7%, 96.2% ± 1.3%, and 97.2% ± 2.5%, respectively, as detected by flow cytometry. These adNSCs can further differentiate into astrocytes, oligodendrocytes, and functional neurons, which were able to generate tetrodotoxin-sensitive sodium current. Additionally, we found that the neural differentiation of hAD-MSCs were significantly suppressed by Sox1 interference, and what's more, Step1 was a key step for the following induction, probably because it was associated with the initiation and nuclear translocation of Sox1, an important transcriptional factor for neural development. Finally, we observed that bone morphogenetic protein signal was inhibited, and Wnt/β-catenin signal was activated during inducing process, and both signals were related with Sox1 expression. In conclusion, we successfully established a three-step inducing protocol to derive NSCs from hAD-MSCs with high purity by Sox1 activation. These findings might enable to acquire enough autologous transplantable NSCs for the therapy of neurodegenerative diseases in clinic.

Tear geometry at active STEPs: an analogue model approach

NASA Astrophysics Data System (ADS)

Broerse, Taco; Sokoutis, Dimitrios; Willingshofer, Ernst; Govers, Rob

2017-04-01

At the lateral end of a subduction zone, tearing of lithosphere is the result of subduction of oceanic lithosphere while adjacent buoyant continental lithosphere stays at the surface. The location of lithospheric tearing is called a Subduction-Transform-Edge-Propagator (STEP), which continuously extends the plate boundary between overriding plate and continental lithosphere. One of our areas of interest is the southern Caribbean where Atlantic lithosphere subducts below the Caribbean plate. Mantle tomography suggests a clear southern edge of the Lesser Antilles slab, which makes the boundary between the Caribbean and South America a clear STEP candidate. At the surface, the San Sebastián/El Pilar fault zone forms the plate boundary between the Caribbean and South America and the active STEP is located near Trinidad. For the deeper part of the damage/shear zone, some information is available from a recent 3D gravity study: significant lateral variability in densities of the lithospheric mantle to the south of the STEP fault zone. The low-density zone may result from higher sub-crustal temperatures, such as would arise from an asthenospheric window resulting from detachment. Interpreted in this way, the mantle part of the damage zone may be 200-250 km wide. So, while the location of the plate boundary at the surface is relatively well resolved, little is known about the deeper continuation of the active STEP in the mantle lithosphere. We study the evolution of the tearing process at a STEP using analogue models. In our models we use silicone putty (lithosphere) and glucose (asthenosphere). Solely gravitational forces resulting from density differences between oceanic lithosphere and asthenosphere drive our model. Lithospheric tearing commences after subduction has initiated. The geometry of the tear varies with the rheology of the lithosphere and asthenosphere, particularly Newtonian versus power-law. We investigate the dependence on model parameters of the width of the tearing zone and the depth at which tearing occurs.

Long-Term International Space Station (ISS) Risk Reduction Activities

NASA Astrophysics Data System (ADS)

Fodroci, M. P.; Gafka, G. K.; Lutomski, M. G.; Maher, J. S.

2012-01-01

As the assembly of the ISS nears completion, it is worthwhile to step back and review some of the actions pursued by the Program in recent years to reduce risk and enhance the safety and health of ISS crewmembers, visitors, and space flight participants. While the initial ISS requirements and design were intended to provide the best practicable levels of safety, it is always possible to further reduce risk - given the determination, commitment, and resources to do so. The following is a summary of some of the steps taken by the ISS Program Manager, by our International Partners, by hardware and software designers, by operational specialists, and by safety personnel to continuously enhance the safety of the ISS, and to reduce risk to all crewmembers. While years of work went into the development of ISS requirements, there are many things associated with risk reduction in a Program like the ISS that can only be learned through actual operational experience. These risk reduction activities can be divided into roughly three categories: Areas that were initially noncompliant which have subsequently been brought into compliance or near compliance (i.e., Micrometeoroid and Orbital Debris [MMOD] protection, acoustics) Areas where initial design requirements were eventually considered inadequate and were subsequently augmented (i.e., Toxicity Hazard Level- 4 [THL] materials, emergency procedures, emergency equipment, control of drag-throughs) Areas where risks were initially underestimated, and have subsequently been addressed through additional mitigation (i.e., Extravehicular Activity [EVA] sharp edges, plasma shock hazards) Due to the hard work and cooperation of many parties working together across the span of more than a decade, the ISS is now a safer and healthier environment for our crew, in many cases exceeding the risk reduction targets inherent in the intent of the original design. It will provide a safe and stable platform for utilization and discovery for years to come.

Long-Term International Space Station (ISS) Risk Reduction Activities

NASA Technical Reports Server (NTRS)

Forroci, Michael P.; Gafka, George K.; Lutomski, Michael G.; Maher, Jacilyn S.

2011-01-01

As the assembly of the ISS nears completion, it is worthwhile to step back and review some of the actions pursued by the Program in recent years to reduce risk and enhance the safety and health of ISS crewmembers, visitors, and space flight participants. While the initial ISS requirements and design were intended to provide the best practicable levels of safety, it is always possible to further reduce risk given the determination, commitment, and resources to do so. The following is a summary of some of the steps taken by the ISS Program Manager, by our International Partners, by hardware and software designers, by operational specialists, and by safety personnel to continuously enhance the safety of the ISS, and to reduce risk to all crewmembers. While years of work went into the development of ISS requirements, there are many things associated with risk reduction in a Program like the ISS that can only be learned through actual operational experience. These risk reduction activities can be divided into roughly three categories: Areas that were initially noncompliant which have subsequently been brought into compliance or near compliance (i.e., Micrometeoroid and Orbital Debris [MMOD] protection, acoustics) Areas where initial design requirements were eventually considered inadequate and were subsequently augmented (i.e., Toxicity hazard level-4 materials, emergency procedures, emergency equipment, control of drag-throughs) Areas where risks were initially underestimated, and have subsequently been addressed through additional mitigation (i.e., Extravehicular Activity [EVA] sharp edges, plasma shock hazards). Due to the hard work and cooperation of many parties working together across the span of more than a decade, the ISS is now a safer and healthier environment for our crew, in many cases exceeding the risk reduction targets inherent in the intent of the original design. It will provide a safe and stable platform for utilization and discovery for years to come.

Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells

PubMed Central

Truong, Lan N.; Li, Yongjiang; Shi, Linda Z.; Hwang, Patty Yi-Hwa; He, Jing; Wang, Hailong; Razavian, Niema; Berns, Michael W.; Wu, Xiaohua

2013-01-01

Microhomology-mediated end joining (MMEJ) is a major pathway for Ku-independent alternative nonhomologous end joining, which contributes to chromosomal translocations and telomere fusions, but the underlying mechanism of MMEJ in mammalian cells is not well understood. In this study, we demonstrated that, distinct from Ku-dependent classical nonhomologous end joining, MMEJ—even with very limited end resection—requires cyclin-dependent kinase activities and increases significantly when cells enter S phase. We also showed that MMEJ shares the initial end resection step with homologous recombination (HR) by requiring meiotic recombination 11 homolog A (Mre11) nuclease activity, which is needed for subsequent recruitment of Bloom syndrome protein (BLM) and exonuclease 1 (Exo1) to DNA double-strand breaks (DSBs) to promote extended end resection and HR. MMEJ does not require S139-phosphorylated histone H2AX (γ-H2AX), suggesting that initial end resection likely occurs at DSB ends. Using a MMEJ and HR competition repair substrate, we demonstrated that MMEJ with short end resection is used in mammalian cells at the level of 10–20% of HR when both HR and nonhomologous end joining are available. Furthermore, MMEJ is used to repair DSBs generated at collapsed replication forks. These studies suggest that MMEJ not only is a backup repair pathway in mammalian cells, but also has important physiological roles in repairing DSBs to maintain cell viability, especially under genomic stress. PMID:23610439

Kinetics of force recovery following length changes in active skinned single fibres from rabbit psoas muscle

PubMed Central

Burton, Kevin; Simmons, Robert M; Sleep, John; Smith, David A

2006-01-01

Redevelopment of isometric force following shortening of skeletal muscle is thought to result from a redistribution of cross-bridge states. We varied the initial force and cross-bridge distribution by applying various length-change protocols to active skinned single fibres from rabbit psoas muscle, and observed the effect on the slowest phase of recovery (‘late recovery’) that follows transient changes. In response to step releases that reduced force to near zero (∼8 nm (half sarcomere)−1) or prolonged shortening at high velocity, late recovery was well described by two exponentials of approximately equal amplitude and rate constants of ∼2 s−1 and ∼9 s−1 at 5°C. When a large restretch was applied at the end of rapid shortening, recovery was accelerated by (1) the introduction of a slow falling component that truncated the rise in force, and (2) a relative increase in the contribution of the fast exponential component. The rate of the slow fall was similar to that observed after a small isometric step stretch, with a rate of 0.4–0.8 s−1, and its effects could be reversed by reducing force to near zero immediately after the stretch. Force at the start of late recovery was varied in a series of shortening steps or ramps in order to probe the effect of cross-bridge strain on force redevelopment. The rate constants of the two components fell by 40–50% as initial force was raised to 75–80% of steady isometric force. As initial force increased, the relative contribution of the fast component decreased, and this was associated with a length constant of about 2 nm. The results are consistent with a two-state strain-dependent cross-bridge model. In the model there is a continuous distribution of recovery rate constants, but two-exponential fits show that the fast component results from cross-bridges initially at moderate positive strain and the slow component from cross-bridges at high positive strain. PMID:16497718

Positive feedback of NR2B-containing NMDA receptor activity is the initial step toward visual imprinting: a model for juvenile learning.

PubMed

Nakamori, Tomoharu; Sato, Katsushige; Kinoshita, Masae; Kanamatsu, Tomoyuki; Sakagami, Hiroyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2015-01-01

Imprinting in chicks is a good model for elucidating the processes underlying neural plasticity changes during juvenile learning. We recently reported that neural activation of a telencephalic region, the core region of the hyperpallium densocellulare (HDCo), was critical for success of visual imprinting, and that N-Methyl-D-aspartic (NMDA) receptors containing the NR2B subunit (NR2B/NR1) in this region were essential for imprinting. Using electrophysiological and multiple-site optical imaging techniques with acute brain slices, we found that long-term potentiation (LTP) and enhancement of NR2B/NR1 currents in HDCo neurons were induced in imprinted chicks. Enhancement of NR2B/NR1 currents as well as an increase in surface NR2B expression occurred even following a brief training that was too weak to induce LTP or imprinting behavior. This means that NR2B/NR1 activation is the initial step of learning, well before the activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors which induces LTP. We also showed that knockdown of NR2B/NR1 inhibited imprinting, and inversely, increasing the surface NR2B expression by treatment with a casein kinase 2 inhibitor successfully reduced training time required for imprinting. These results suggest that imprinting stimuli activate post-synaptic NR2B/NR1 in HDCo cells, increase NR2B/NR1 signaling through up-regulation of its expression, and induce LTP and memory acquisition. The study investigated the neural mechanism underlying juvenile learning. In the initial stage of chick imprinting, NMDA receptors containing the NMDA receptor subunit 2B (NR2B) are activated, surface expression of NR2B/NR1 (NMDA receptor subunit 1) is up-regulated, and consequently long-term potentiation is induced in the telencephalic neurons. We suggest that the positive feedback in the NR2B/NR1 activation is a unique process of juvenile learning, exhibiting rapid memory acquisition. © 2014 International Society for Neurochemistry.

Examining racial and ethnic minority differences among YMSM during recruitment for an online HIV prevention intervention study.

PubMed

Du Bois, Steve N; Johnson, Sarah E; Mustanski, Brian

2012-08-01

HIV disproportionately affects racial and ethnic minority young men who have sex with men (YMSM). HIV prevention research does not include these YMSM commensurate to their HIV burden. We examined racial and ethnic differences during a unique three-step recruitment process for an online, YMSM HIV prevention intervention study (N = 660). Step one was completed in-person; steps two and three online. Fewer Black and Latino YMSM completed step two-initiating online participation-than White YMSM. Internet use frequency accounted for the Latino versus White difference in initiating online participation, but not the Black versus White difference. Future online HIV prevention interventions recruiting diverse YMSM should focus on initiating online engagement among Black participants.

Examining Racial and Ethnic Minority Differences among YMSM during Recruitment for an Online HIV Prevention Intervention Study

PubMed Central

Du Bois, Steve N.; Johnson, Sarah E.; Mustanski, Brian

2011-01-01

HIV disproportionately affects racial and ethnic minority young men who have sex with men (YMSM). HIV prevention research does not include these YMSM commensurate to their HIV burden. We examined racial and ethnic differences during a unique three-step recruitment process for an online, YMSM HIV prevention intervention study (N=660). Step one was completed in-person; steps two and three online. Fewer Black and Latino YMSM completed step two – initiating online participation – than White YMSM. Internet use frequency accounted for the Latino vs. White difference in initiating online participation, but not the Black vs. White difference. Future online HIV prevention interventions recruiting diverse YMSM should focus on initiating online engagement among Black participants. PMID:21986869

An internet-based virtual coach to promote physical activity adherence in overweight adults: randomized controlled trial.

PubMed

Watson, Alice; Bickmore, Timothy; Cange, Abby; Kulshreshtha, Ambar; Kvedar, Joseph

2012-01-26

Addressing the obesity epidemic requires the development of effective, scalable interventions. Pedometers and Web-based programs are beneficial in increasing activity levels but might be enhanced by the addition of nonhuman coaching. We hypothesized that a virtual coach would increase activity levels, via step count, in overweight or obese individuals beyond the effect observed using a pedometer and website alone. We recruited 70 participants with a body mass index (BMI) between 25 and 35 kg/m(2) from the Boston metropolitan area. Participants were assigned to one of two study arms and asked to wear a pedometer and access a website to view step counts. Intervention participants also met with a virtual coach, an automated, animated computer agent that ran on their home computers, set goals, and provided personalized feedback. Data were collected and analyzed in 2008. The primary outcome measure was change in activity level (percentage change in step count) over the 12-week study, split into four 3-week time periods. Major secondary outcomes were change in BMI and participants' satisfaction. The mean age of participants was 42 years; the majority of participants were female (59/70, 84%), white (53/70, 76%), and college educated (68/70, 97%). Of the initial 70 participants, 62 completed the study. Step counts were maintained in intervention participants but declined in controls. The percentage change in step count between those in the intervention and control arms, from the start to the end, did not reach the threshold for significance (2.9% vs -12.8% respectively, P = .07). However, repeated measures analysis showed a significant difference when comparing percentage changes in step counts between control and intervention participants over all time points (analysis of variance, P = .02). There were no significant changes in secondary outcome measures. The virtual coach was beneficial in maintaining activity level. The long-term benefits and additional applications of this technology warrant further study. ClinicalTrials.gov NCT00792207; http://clinicaltrials.gov/ct2/show/NCT00792207 (Archived by WebCite at http://www.webcitation.org/63sm9mXUD).

RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells

PubMed Central

Im, Jun-Sub; Park, Soon-Young; Cho, Won-Ho; Bae, Sung-Ho; Hurwitz, Jerard; Lee, Joon-Kyu

2015-01-01

Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells. PMID:25602958

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

PubMed

Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

2018-04-10

Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Rocket-Based Combined Cycle Activities in the Advanced Space Transportation Program Office

NASA Technical Reports Server (NTRS)

Hueter, Uwe; Turner, James

1999-01-01

NASA's Office of Aero-Space Technology (OAST) has established three major goals, referred to as, "The Three Pillars for Success". The Advanced Space Transportation Program Office (ASTP) at the NASA's Marshall Space Flight Center (MSFC) in Huntsville, Ala. focuses on future space transportation technologies Under the "Access to Space" pillar. The Core Technologies Project, part of ASTP, focuses on the reusable technologies beyond those being pursued by X-33. One of the main activities over the past two and a half years has been on advancing the rocket-based combined cycle (RBCC) technologies. In June of last year, activities for reusable launch vehicle (RLV) airframe and propulsion technologies were initiated. These activities focus primarily on those technologies that support the decision to determine the path this country will take for Space Shuttle and RLV. This year, additional technology efforts in the reusable technologies will be awarded. The RBCC effort that was completed early this year was the initial step leading to flight demonstrations of the technology for space launch vehicle propulsion.

Hemolytic activity in Flavobacterium psychrophilum is a contact-dependent, two-step mechanism and differently expressed in smooth and rough phenotypes.

PubMed

Högfors-Rönnholm, Eva; Wiklund, Tom

2010-12-01

The hemolytic activity of cells of smooth and rough phenotypic variants of the Gram-negative fish pathogen Flavobacterium psychrophilum was investigated in two different assays, a microplate and an agarose hemolysis assay, using rainbow trout erythrocytes. The smooth cells showed a high and the rough cells a negligible, concentration dependent, hemolytic activity in the microplate assay. Both smooth and rough cells showed a rather weak hemolytic activity, with two distinct hemolytic patterns, in the agarose assay. The hemolytic activity of the cells was not regulated by iron availability and cell-free extracellular products did not show any hemolytic activity. The smooth cells, in contrast to the rough cells, showed a high ability to agglutinate erythrocytes and both hemagglutination and hemolytic activity was impaired by treatment of the cells with sialic acid. The hemolytic activity was furthermore reduced after proteolytic and heat treatment of the cells. The results from the present study suggest that the hemolytic activity in F. psychrophilum is highly expressed in the smooth phenotype, and that it is a contact-dependent and two-step mechanism that is initiated by the binding of the bacterial cells to the erythrocytes through sialic acid-binding lectins and then executed by thermolabile proteinaceous hemolysins. Copyright © 2010 Elsevier Ltd. All rights reserved.

Results of a prospective clinical study on the diagnostic performance of standard magnetic resonance imaging in comparison to a combination of 3T MRI and additional CT imaging in Kienböck's disease.

PubMed

Stahl, Stephane; Hentschel, Pascal; Ketelsen, Dominik; Grosse, Ulrich; Held, Manuel; Wahler, Theodora; Syha, Roland; Schaller, Hans-Eberhard; Nikolaou, Konstantin; Grözinger, Gerd

2017-05-01

This prospective clinical study examined standard wrist magnetic resonance imaging (MRI) examinations and the incremental value of computed tomography (CT) in the diagnosis of Kienböck's disease (KD) with regard to reliability and precision in the different diagnostic steps during diagnostic work-up. Sixty-four consecutive patients referred between January 2009 and January 2014 with positive initial suspicion of KD according to external standard wrist MRI were prospectively included (step one). Institutional review board approval was obtained. Clinical examination by two handsurgeons were followed by wrist radiographs (step two), ultrathin-section CT, and 3T contrast-enhanced MRI (step three). Final diagnosis was established in a consensus conference involving all examiners and all examinations results available from step three. In 12/64 patients, initial suspicion was discarded at step two and in 34/64 patients, the initial suspicion of KD was finally discarded at step three. The final external MRI positive predictive value was 47%. The most common differential diagnoses at step three were intraosseous cysts (n=15), lunate pseudarthrosis (n=13), and ulnar impaction syndrome (n=5). A correlation between radiograph-based diagnoses (step two) with final diagnosis (step three) showed that initial suspicion of stage I KD had the lowest sensitivity for correct diagnosis (2/11). Technical factors associated with a false positive external MRI KD diagnosis were not found. Standard wrist MRI should be complemented with thin-section CT, and interdisciplinary interpretation of images and clinical data, to increase diagnostic accuracy in patients with suspected KD. Copyright © 2017. Published by Elsevier B.V.

Euro-VO-Coordination of virtual observatory activities in Europe

NASA Astrophysics Data System (ADS)

Genova, Françoise; Allen, Mark G.; Arviset, Christophe; Lawrence, Andy; Pasian, Fabio; Solano, Enrique; Wambsganss, Joachim

2015-06-01

The European Virtual Observatory Euro-VO has been coordinating European VO activities through a series of projects co-funded by the European Commission over the last 15 years. The bulk of VO work in Europe is ensured by the national VO initiatives and those of intergovernmental agencies. VO activities at the European level coordinate the work in support of the three "pillars" of the Virtual Observatory: support to the scientific community, take-up by the data providers, and technological activities. Several Euro-VO projects have also provided direct support to selected developments and prototyping. This paper explains the methodology used by Euro-VO over the years. It summarises the activities which were performed and their evolutions at different stages of the development of the VO, explains the Euro-VO role with respect to the international and national levels of VO activities, details the lessons learnt for best practices for the coordination of the VO building blocks, and the liaison with other European initiatives, documenting the added-value of European coordination. Finally, the current status and next steps of Euro-VO are briefly addressed.

[Effect of SO2 volume fraction in flue gas on the adsorption behaviors adsorbed by ZL50 activated carbon and kinetic analysis].

PubMed

Gao, Ji-xian; Wang, Tie-feng; Wang, Jin-fu

2010-05-01

The influence of SO2 dynamic adsorption behaviors using ZL50 activated carbon for flue gas desulphurization and denitrification under different SO2 volume fraction was investigated experimentally, and the kinetic analysis was conducted by kinetic models. With the increase of SO2 volume fraction in flue gas, the SO2 removal ratio and the activity ratio of ZL50 activated carbon decreased, respectively, and SO2 adsorption rate and capacity increased correspondingly. The calculated results indicate that Bangham model has the best prediction effect, the chemisorption processes of SO2 was significantly affected by catalytic oxidative reaction. The adsorption rate constant of Lagergren's pseudo first order model increased with the increase of inlet SO, volume fraction, which indicated that catalytic oxidative reaction of SO2 adsorbed by ZL50 activated carbon may be the rate controlling step in earlier adsorption stage. The Lagergren's and Bangham's initial adsorption rate were deduced and defined, respectively. The Ho's and Elovich's initial adsorption rate were also deduced in this paper. The Bangham's initial adsorption rate values were defined in good agreement with those of experiments. The defined Bangham's adsorptive reaction kinetic model can describe the SO2 dynamic adsorption rate well. The studied results indicated that the SO2 partial order of initial reaction rate was one or adjacent to one, while the O2 and water vapor partial order of initial reaction rate were constants ranging from 0.15-0.20 and 0.45-0.50, respectively.

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

Fan, Yue; Iwashita, Takuya; Egami, Takeshi

Complex states in glasses can be neatly expressed by the potential energy landscape (PEL). But, because PEL is highly multi-dimensional it is difficult to describe how the system moves around in PEL. We demonstrate that it is possible to predict the evolution of macroscopic state in a metallic glass, such as ageing and rejuvenation, through a set of simple equations describing excitations in the PEL. The key to this simplification is the realization that the step of activation from the initial state to the saddle point in PEL and the following step of relaxation to the final state are essentiallymore » decoupled. Furthermore, the model shows that the interplay between activation and relaxation in PEL is the key driving force that simultaneously explains both the equilibrium of supercooled liquid and the thermal hysteresis observed in experiments. It further predicts anomalous peaks in truncated thermal scanning, validated by independent molecular dynamics simulation.« less

Building international collaborative capacity: contributions of community psychologists to a European network.

PubMed

García-Ramírez, Manuel; Paloma, Virginia; Suarez-Balcazar, Yolanda; Balcazar, Fabricio

2009-09-01

Europe is in the process of building a more participative, just, and inclusive European Union. The European Social Fund, which is an initiative developed to actively promote multinational partnerships that address pressing social issues, is a good example of the European transformation. This article describes the steps taken to develop and evaluate the activities of an international network promoting collaborative capacity among regional partners involved in the prevention of labor discrimination toward immigrants in three European countries-Spain, Belgium, and Italy. An international team of community psychologists proposed an empowering approach to assess the collaborative capacity of the network. This approach consisted of three steps: (1) establishing a collaborative relationship among partners, (2) building collaborative capacity, and (3) evaluating the collaborative capacity of the network. We conclude with lessons learned from the process and provide recommendations for addressing the challenges inherent in international collaboration processes.

The role of template superhelicity in the initiation of bacteriophage lambda DNA replication.

PubMed Central

Alfano, C; McMacken, R

1988-01-01

The prepriming steps in the initiation of bacteriophage lambda DNA replication depend on the action of the lambda O and P proteins and on the DnaB helicase, single-stranded DNA binding protein (SSB), and DnaJ and DnaK heat shock proteins of the E. coli host. The binding of multiple copies of the lambda O protein to the phage replication origin (ori lambda) initiates the ordered assembly of a series of nucleoprotein structures that form at ori lambda prior to DNA unwinding, priming and DNA synthesis steps. Since the initiation of lambda DNA replication is known to occur only on supercoiled templates in vivo and in vitro, we examined how the early steps in lambda DNA replication are influenced by superhelical tension. All initiation complexes formed prior to helicase-mediated DNA-unwinding form with high efficiency on relaxed ori lambda DNA. Nonetheless, the DNA templates in these structures must be negatively supertwisted before they can be replicated. Once DNA helicase unwinding is initiated at ori lambda, however, later steps in lambda DNA replication proceed efficiently in the absence of superhelical tension. We conclude that supercoiling is required during the initiation of lambda DNA replication to facilitate entry of a DNA helicase, presumably the DnaB protein, between the DNA strands. Images PMID:2847118

Relationships between Neighborhood Walkability and Objectively Measured Physical Activity Levels in Hemodialysis Patients.

PubMed

Han, Maggie; Ye, Xiaoling; Preciado, Priscila; Williams, Schantel; Campos, Israel; Bonner, Marcee; Young, Candace; Marsh, Daniel; Larkin, John W; Usvyat, Len A; Maddux, Franklin W; Pecoits-Filho, Roberto; Kotanko, Peter

2018-01-01

Neighborhood walkability is associated with indicators of health in the general population. We explored the association between neighborhood walkability and daily steps in hemodialysis (HD) patients. We measured daily steps over 5 weeks using Fitbit Flex (Fitbit, San Francisco, CA, USA) and retrieved Walk Score® (WS) data by patient's home ZIP code (www.walkscore.com; 0 = poorest walkability; 100 = greatest walkability). HD patients took a mean of 6,393 ± 3,550 steps/day (n = 46). Median WS of the neighborhood where they resided was 28. Patients in an above-median WS (n = 27) neighborhood took significantly more daily steps compared to those (n = 19) in a below-median WS neighborhood (7,514 ± 3,900 vs. 4,800 ± 2,228 steps/day; p < 0.001, t test). Daily steps and WS were directly correlated (R = 0.425; p = 0.0032, parametric test; R = 0.359, p = 0.0143, non-parametric test). This is the first study conducted among HD patients to indicate a direct relationship between neighborhood walkability and the actual steps taken. These results should be considered when designing initiatives to increase and improvise exercise routines in HD populations. © 2018 S. Karger AG, Basel.

Two-step rocket engine bipropellant valve concept

NASA Technical Reports Server (NTRS)

Capps, J. E.; Ferguson, R. E.; Pohl, H. O.

1969-01-01

Initiating combustion of altitude control rocket engines in a precombustion chamber of ductile material reduces high pressure surges generated by hypergolic propellants. Two-step bipropellant valve concepts control initial propellant flow into precombustion chamber and subsequent full flow into main chamber.

Higher mobility scores in patients with cystic fibrosis are associated with better lung function.

PubMed

Thobani, Aneesha; Alvarez, Jessica A; Blair, Shaina; Jackson, Kaila; Gottlieb, Eric R; Walker, Seth; Tangpricha, Vin

2015-01-01

The purpose of this study was to determine whether mobility and physical activity were associated with lung function in adults with cystic fibrosis (CF). This was a prospective cohort observational study in an urban, academic, specialized care center. Participants were ambulatory, nonhospitalized adults with CF. Mobility was assessed monthly by the Life-Space Assessment (LSA) questionnaire and quarterly by pedometer. Lung function was assessed by spirometry. Twenty-seven subjects participated. Subjects recorded mean pedometer steps of 20,213 ± 11,331 over three days and FEV1% predicted of 77.48% ± 22.60% over one year. The LSA score at enrollment was correlated with initial pedometer steps (r = 0.42 and P = 0.03), and mean LSA score over one year was correlated with mean number of steps (r = 0.51 and P = 0.007). LSA mobility and pedometer scores were correlated with FEV1% predicted at enrollment and throughout the study. Mobility and physical activity measured by LSA questionnaire and pedometer are positively associated with lung function in adults with CF. This study confirms the importance of mobility and physical activity and supports the utility of a simple office-based questionnaire as a measure of mobility in adults with CF.

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

PubMed

Wang, F; Jiao, P; Qi, M; Frezza, M; Dou, Q P; Yan, B

2010-01-01

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation

PubMed Central

Vincent, Heather A.; Ziehr, Benjamin; Moorman, Nathaniel J.

2016-01-01

mRNA translation requires the ordered assembly of translation initiation factors and ribosomal subunits on a transcript. Host signaling pathways regulate each step in this process to match levels of protein synthesis to environmental cues. In response to infection, cells activate multiple defenses that limit viral protein synthesis, which viruses must counteract to successfully replicate. Human cytomegalovirus (HCMV) inhibits host defenses that limit viral protein expression and manipulates host signaling pathways to promote the expression of both host and viral proteins necessary for virus replication. Here we review key regulatory steps in mRNA translation, and the strategies used by HCMV to maintain protein synthesis in infected cells. PMID:27089357

Conducting survey research at nursing conferences.

PubMed

Sleutel, M R

2001-01-01

Conferences can provide large numbers of potential subjects in one location, yet there is little published guidance on how to collect data at a conference site. A computer search revealed no citations on this topic. This article outlines a systematic strategy to plan and perform research at conferences. This article provides a step-by-step process to guide researchers in planning and conducting survey research at conferences. Initial components in planning data collection at a conference include making a timeline and getting permission. Detailed advanced planning involves specific strategies for attracting participants, and for distributing and collecting the questionnaires. Travel provisions and on-site logistical approaches are explained, followed by suggestions for post-conference activities.

Chemoselective Nitro Group Reduction and Reductive Dechlorination Initiate Degradation of 2-Chloro-5-Nitrophenol by Ralstonia eutropha JMP134

PubMed Central

Schenzle, Andreas; Lenke, Hiltrud; Spain, Jim C.; Knackmuss, Hans-Joachim

1999-01-01

Ralstonia eutropha JMP134 utilizes 2-chloro-5-nitrophenol as a sole source of nitrogen, carbon, and energy. The initial steps for degradation of 2-chloro-5-nitrophenol are analogous to those of 3-nitrophenol degradation in R. eutropha JMP134. 2-Chloro-5-nitrophenol is initially reduced to 2-chloro-5-hydroxylaminophenol, which is subject to an enzymatic Bamberger rearrangement yielding 2-amino-5-chlorohydroquinone. The chlorine of 2-amino-5-chlorohydroquinone is removed by a reductive mechanism, and aminohydroquinone is formed. 2-Chloro-5-nitrophenol and 3-nitrophenol induce the expression of 3-nitrophenol nitroreductase, of 3-hydroxylaminophenol mutase, and of the dechlorinating activity. 3-Nitrophenol nitroreductase catalyzes chemoselective reduction of aromatic nitro groups to hydroxylamino groups in the presence of NADPH. 3-Nitrophenol nitroreductase is active with a variety of mono-, di-, and trinitroaromatic compounds, demonstrating a relaxed substrate specificity of the enzyme. Nitrosobenzene serves as a substrate for the enzyme and is converted faster than nitrobenzene. PMID:10347008

Postural adjustment errors reveal deficits in inhibition during lateral step initiation in older adults

PubMed Central

Fuhrman, Susan I.; Redfern, Mark S.; Jennings, J. Richard; Perera, Subashan; Nebes, Robert D.; Furman, Joseph M.

2013-01-01

Postural dual-task studies have demonstrated effects of various executive function components on gait and postural control in older adults. The purpose of the study was to explore the role of inhibition during lateral step initiation. Forty older adults participated (range 70–94 yr). Subjects stepped to the left or right in response to congruous and incongruous visual cues that consisted of left and right arrows appearing on left or right sides of a monitor. The timing of postural adjustments was identified by inflection points in the vertical ground reaction forces (VGRF) measured separately under each foot. Step responses could be classified into preferred and nonpreferred step behavior based on the number of postural adjustments that were made. Delays in onset of the first postural adjustment (PA1) and liftoff (LO) of the step leg during preferred steps progressively increased among the simple, choice, congruous, and incongruous tasks, indicating interference in processing the relevant visuospatial cue. Incongruous cues induced subjects to make more postural adjustments than they typically would (i.e., nonpreferred steps), representing errors in selection of the appropriate motor program. During these nonpreferred steps, the onset of the PA1 was earlier than during the preferred steps, indicating a failure to inhibit an inappropriate initial postural adjustment. The functional consequence of the additional postural adjustments was a delay in the LO compared with steps in which they did not make an error. These results suggest that deficits in inhibitory function may detrimentally affect step decision processing, by delaying voluntary step responses. PMID:23114211

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger

PubMed Central

Mille, Marie‐Laure

2016-01-01

Abstract Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. PMID:26915664

Sensory gating for the initiation of the swing phase in different directions of human infant stepping.

PubMed

Pang, Marco Y C; Yang, Jaynie F

2002-07-01

Humans can make smooth, continuous transitions in walking direction from forward to backward. Thus, the processing of sensory input must allow a similar continuum of possibilities. Hip extension and reduced load are two important conditions that control the transition from the stance to swing phase during forward stepping in human infants. The purpose of this study was to determine whether the same factors also regulate the initiation of the swing phase in other directions of stepping. Thirty-seven infants between the ages of 5 and 13 months were studied during supported forward and sideways stepping on a treadmill. Disturbances were elicited by placing a piece of cardboard under the foot and pulling the cardboard in different directions. In this way, the leg was displaced in a particular direction and simultaneously unloaded. We observed whether the swing phase was immediately initiated after the application of disturbances in various directions. Electromyography, vertical ground reaction forces, and hip motion in frontal and sagittal planes were recorded. The results showed that the most potent sensory input to initiate the swing phase depends on the direction of stepping. Although low load was always necessary to initiate swing for all directions of walking, the preferred hip position was always one directly opposite the direction of walking. The results indicated the presence of selective gating of sensory input from the legs as a function of the direction of stepping.

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 initiate...

Improving efficiency and safety in external beam radiation therapy treatment delivery using a Kaizen approach.

PubMed

Kapur, Ajay; Adair, Nilda; O'Brien, Mildred; Naparstek, Nikoleta; Cangelosi, Thomas; Zuvic, Petrina; Joseph, Sherin; Meier, Jason; Bloom, Beatrice; Potters, Louis

Modern external beam radiation therapy treatment delivery processes potentially increase the number of tasks to be performed by therapists and thus opportunities for errors, yet the need to treat a large number of patients daily requires a balanced allocation of time per treatment slot. The goal of this work was to streamline the underlying workflow in such time-interval constrained processes to enhance both execution efficiency and active safety surveillance using a Kaizen approach. A Kaizen project was initiated by mapping the workflow within each treatment slot for 3 Varian TrueBeam linear accelerators. More than 90 steps were identified, and average execution times for each were measured. The time-consuming steps were stratified into a 2 × 2 matrix arranged by potential workflow improvement versus the level of corrective effort required. A work plan was created to launch initiatives with high potential for workflow improvement but modest effort to implement. Time spent on safety surveillance and average durations of treatment slots were used to assess corresponding workflow improvements. Three initiatives were implemented to mitigate unnecessary therapist motion, overprocessing of data, and wait time for data transfer defects, respectively. A fourth initiative was implemented to make the division of labor by treating therapists as well as peer review more explicit. The average duration of treatment slots reduced by 6.7% in the 9 months following implementation of the initiatives (P = .001). A reduction of 21% in duration of treatment slots was observed on 1 of the machines (P < .001). Time spent on safety reviews remained the same (20% of the allocated interval), but the peer review component increased. The Kaizen approach has the potential to improve operational efficiency and safety with quick turnaround in radiation therapy practice by addressing non-value-adding steps characteristic of individual department workflows. Higher effort opportunities are identified to guide continual downstream quality improvements. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

CDC Kerala 1: Organization of clinical child development services (1987-2013).

PubMed

Nair, M K C; George, Babu; Nair, G S Harikumaran; Bhaskaran, Deepa; Leena, M L; Russell, Paul Swamidhas Sudhakar

2014-12-01

The main objective of establishing the Child Development Centre (CDC), Kerala for piloting comprehensive child adolescent development program in India, has been to understand the conceptualization, design and scaling up of a pro-active positive child development initiative, easily replicable all over India. The process of establishing the Child Development Centre (CDC) Kerala for research, clinical services, training and community extension services over the last 25 y, has been as follows; Step 1: Conceptualization--The life cycle approach to child development; Step 2: Research basis--CDC model early stimulation is effective; Step 3: Development and validation of seven simple developmental screening tools; Step 4: CDC Diagnostic services--Ultrasonology and genetic, and metabolic laboratory; Step 5: Developing seven intervention packages; Step 6: Training--Post graduate diploma in clinical child development; Step 7: CDC Clinic Services--seven major ones; Step 8: CDC Community Services--Child development referral units; Step 9: Community service delivery models--Childhood disability and for adolescent care counselling projects; Step 10: National capacity building--Four child development related courses. CDC Kerala follow-up and clinic services are offered till 18 y of age and premarital counselling till 24 y of age as shown in "CDC Kerala Clinic Services Flow Chart" and 74,291 children have availed CDC clinic services in the last 10 y. CDC Kerala is the first model for comprehensive child adolescent development services using a lifecycle approach in the Government sector and hence declared as the collaborative centre for Rashtriya Bal Swasthya Karyakram (RBSK), in Kerala.

Polymer brush covalently attached to OH-functionalized mica surface via surface-initiated ATRP: control of grafting density and polymer chain length.

PubMed

Lego, Béatrice; François, Marion; Skene, W G; Giasson, Suzanne

2009-05-05

The controlled grafting density of poly(tert-butyl acrylate) was studied on OH-activated mica substrates via surface-initiated atom-transfer radical polymerization (ATRP). By properly adjusting parameters such as the immobilization reaction time and the concentration of an ATRP initiator, a wide range of initiator surface coverages and hence polymer densities on mica were possible. The covalently immobilized initiator successfully promoted the polymerization of tert-butyl acrylate on mica surfaces. The resulting polymer layer thickness was measured by AFM using a step-height method. Linear relationships of the polymer thickness with respect to the molecular weight of the free polymer and with respect to the monomer conversion were observed, suggesting that ATRP is well controlled and relatively densely end-grafted layers were obtained. The polymer grafting density controlled by adjusting the initiator surface coverage was confirmed by the polymer layer swelling capacity and film thickness measurements.

Chemotherapy and Biochemistry of Leishmania

DTIC Science & Technology

1985-12-01

Leishmania- sis is initiated when sandflies inject the extracellular prcmastigate form of the parasite into the skin . The promastigotes are...precipitate from the protamine sulfate step was removed by centri- fugation at 15,000 rpm for 15 min at 40. The supernatant was dialyzed in 2 L of...Fig. 13. Only two protein bands could be detected when stained with commassie blue . RNA polymerase activity could not be detected when gels were

A Study of Issues Related to Recruitment of Enlisted Personnel for the Reserve Components. Volume 1. Major Findings and Recommendations 1979 Tracking Study. Wave 2

DTIC Science & Technology

1980-09-01

for service and target the 19 to 21 year old segment of NPS males and females. Rationale : Changes in the initial active duty training and the offering... Green Veterans Questionnaire .......................... .Yellow -Reinterview Questionnaire .......... ........ Bu DETAILED TABLE OF...of ".he Standard Enlistment Propensity Measure........... ...................... 2100 9.4 Behavioral Steps Toward Enlistment ............... 102 9.5

Impregnated active carbons to control atmospheric emissions: influence of impregnation methodology and raw material on the catalytic activity.

PubMed

Alvim-Ferraz, Maria C M; Gaspar, Carla M T B

2005-08-15

Previous studies have reported the influence of raw material on the catalytic activity of metal oxides impregnated in activated carbons. However, knowledge was as yet quite scarce for impregnation performed before activation. The main objective of the study here reported was the development of such knowledge. Olive stones, pinewood sawdust, nutshells, and almond shells were recycled to prepare the activated carbons. Transition metal oxides (CoO, Co3O4, and CrO3) were impregnated aiming to prepare activated carbons to be used for the complete catalytic oxidation of benzene. When impregnation was performed after activation the impregnated species were deposited on the internal surface, blocking part of the initial porous texture. When impregnation was performed before activation, the metal species acted as catalysts during the activation step, allowing better catalyst distribution on a more well-developed mesoporous texture. Co3O4 was the best catalyst and almond shells were the best support. With this catalyst/support pair a conversion of 90% was possible at 404 K, the lowest temperature of all the carbons studied. Good conversions were obtained at temperatures that guarantee carbon stability (lower than 575 K). It was concluded that activated carbon was a suitable support for metal oxide catalysts aiming for the complete oxidation of benzene, especially when a suitable porous texture is induced, by performing the impregnation step before activation.

How Conformational Dynamics of DNA Polymerase Select Correct Substrates: Experiments and Simulations

PubMed Central

Kirmizialtin, Serdal; Nguyen, Virginia; Johnson, Kenneth A.; Elber, Ron

2012-01-01

Summary Nearly every enzyme undergoes a significant change in structure after binding it’s substrate. New experimental and theoretical analyses of the role of changes in HIV reverse transcriptase structure in selecting a correct substrate are presented. Atomically detailed simulations using the Milestoning method predict a rate and free energy profile of the conformational change commensurate with experimental data. A large conformational change occurring on a ms timescale locks the correct nucleotide at the active site, but promotes release of a mismatched nucleotide. The positions along the reaction coordinate that decide the yield of the reaction are not determined by the chemical step. Rather, the initial steps of weak substrate binding and protein conformational transition significantly enrich the yield of a reaction with a correct substrate, while the same steps diminish the reaction probability of an incorrect substrate. PMID:22483109

Using a split luciferase assay (SLA) to measure the kinetics of cell-cell fusion mediated by herpes simplex virus glycoproteins.

PubMed

Saw, Wan Ting; Matsuda, Zene; Eisenberg, Roselyn J; Cohen, Gary H; Atanasiu, Doina

2015-11-15

Herpes simplex virus (HSV) entry and cell-cell fusion require the envelope proteins gD, gH/gL and gB. We propose that receptor-activated conformational changes to gD activate gH/gL, which then triggers gB (the fusogen) into an active form. To study this dynamic process, we have adapted a dual split protein assay originally developed to study the kinetics of human immunodeficiency virus (HIV) mediated fusion. This assay uses a chimera of split forms of renilla luciferase (RL) and green fluorescent protein (GFP). Effector cells are co-transfected with the glycoproteins and one of the split reporters. Receptor-bearing target cells are transfected with the second reporter. Co-culture results in fusion and restoration of RL, which can convert a membrane permeable substrate into a luminescent product, thereby enabling one to monitor initiation and extent of fusion in live cells in real time. Restoration of GFP can also be studied by fluorescence microscopy. Two sets of split reporters have been developed: the original one allows one to measure fusion kinetics over hours whereas the more recent version was designed to enhance the sensitivity of RL activity allowing one to monitor both initiation and rates of fusion in minutes. Here, we provide a detailed, step-by-step protocol for the optimization of the assay (which we call the SLA for split luciferase assay) using the HSV system. We also show several examples of the power of this assay to examine both the initiation and kinetics of cell-cell fusion by wild type forms of gD, gB, gH/gL of both serotypes of HSV as well as the effect of mutations and antibodies that alter the kinetics of fusion. The SLA can be applied to other viral systems that carry out membrane fusion. Copyright © 2015 Elsevier Inc. All rights reserved.

Using a Split Luciferase Assay (SLA) to measure the kinetics of cell-cell fusion mediated by herpes simplex virus glycoproteins

PubMed Central

Saw, Wan Ting; Matsuda, Zene; Eisenberg, Roselyn J; Cohen, Gary H; Atanasiu, Doina

2015-01-01

Herpes simplex virus (HSV) entry and cell-cell fusion require the envelope proteins gD, gH/gL and gB. We propose that receptor-activated conformational changes to gD activate gH/gL, which then triggers gB (the fusogen) into an active form. To study this dynamic process, we have adapted a dual split protein assay originally developed to study the kinetics of human immunodeficiency virus (HIV) mediated fusion. This assay uses a chimera of split forms of renilla luciferase (RL) and green fluorescent protein (GFP). Effector cells are co-transfected with the glycoproteins and one of the split reporters. Receptor-bearing target cells are transfected with the second reporter. Co-culture results in fusion and restoration of RL, which can convert a membrane permeable substrate into a luminescent product, thereby enabling one to monitor initiation and extent of fusion in live cells in real time. Restoration of GFP can also be studied by fluorescence microscopy. Two sets of split reporters have been developed: the original one allows one to measure fusion kinetics over hours whereas the more recent version was designed to enhance the sensitivity of RL activity allowing one to monitor both initiation and rates of fusion in minutes. Here, we provide a detailed, step-by-step protocol for the optimization of the assay (which we call the SLA for split luciferase assay) using the HSV system. We also show several examples of the power of this assay to examine both the initiation and kinetics of cell-cell fusion by wild type forms of gD, gB, gH/gL of both serotypes of HSV as well as the effect of mutations and antibodies that alter the kinetics of fusion. The SLA can be applied to other viral systems that carry out membrane fusion. PMID:26022509

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger.

PubMed

Rogers, Mark W; Mille, Marie-Laure

2016-08-15

Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation-induced steps that are triggered as fast as or faster than for younger adults. While age-associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step-triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event-triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

A Case of Undiagnosed Craniopharyngioma in an Army Mechanic.

PubMed

Lee, Douglas Y; Mathis, Derek A

2016-02-01

Primary care providers are often the initial evaluators of soldiers presenting with acute eye complaints. It is crucial for these providers to master performing the basic eye examination with a systematic approach. Obtaining a thorough history is an important first step to the eye examination, but providers need to be careful not to narrow the diagnosis solely based on the history. Regardless of the presentation of the ocular complaints, a complete ocular examination must be performed. This article presents a case of brain tumor in an active duty soldier who was initially undiagnosed because of its unusual presentation. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Resuscitator’s perceptions and time for corrective ventilation steps during neonatal resuscitation☆

PubMed Central

Sharma, Vinay; Lakshminrusimha, Satyan; Carrion, Vivien; Mathew, Bobby

2016-01-01

Background The 2010 neonatal resuscitation program (NRP) guidelines incorporate ventilation corrective steps (using the mnemonic – MRSOPA) into the resuscitation algorithm. The perception of neonatal providers, time taken to perform these maneuvers or the effectiveness of these additional steps has not been evaluated. Methods Using two simulated clinical scenarios of varying degrees of cardiovascular compromise –perinatal asphyxia with (i) bradycardia (heart rate – 40 min−1) and (ii) cardiac arrest, 35 NRP certified providers were evaluated for preference to performing these corrective measures, the time taken for performing these steps and time to onset of chest compressions. Results The average time taken to perform ventilation corrective steps (MRSOPA) was 48.9 ± 21.4 s. Providers were less likely to perform corrective steps and proceed directly to endotracheal intubation in the scenario of cardiac arrest as compared to a state of bradycardia. Cardiac compressions were initiated significantly sooner in the scenario of cardiac arrest 89 ± 24 s as compared to severe bradycardia 122 ± 23 s, p < 0.0001. There were no differences in the time taken to initiation of chest compressions between physicians or mid-level care providers or with the level of experience of the provider. Conclusions Effective ventilation of the lungs with corrective steps using a mask is important in most cases of neonatal resuscitation. Neonatal resuscitators prefer early endotracheal intubation and initiation of chest compressions in the presence of asystolic cardiac arrest. Corrective ventilation steps can potentially postpone initiation of chest compressions and may delay return of spontaneous circulation in the presence of severe cardiovascular compromise. PMID:25796996

Childhood Obesity, Physical Activity, and Exercise.

PubMed

Nemet, Dan

2017-02-01

As the incidence of childhood obesity increases, there is a need to promote leisure time physical activity. Traditional approaches to promote the population physical activity levels have shown at best moderate improvements. High percentage of children today carry a cell phone, thus the use of this portable device seems promising for enhancing physical activity. Pokémon Go, is a smartphone game that uses augmented reality, where players are incentivized to get out and walk significant distances to catch the Pokémon. Initial reports suggested increases in the number of steps that players performed, yet this effect of the game was not sustained. Incorporating physical activity into modern technology seems promising, clearly there is need to explore creative ways to achieve a longer term effect.

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 98: Frenchman Flat, Nevada National Security Site, Nevada, Revision 1

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

Irene Farnham and Sam Marutzky

2011-07-01

This CADD/CAP follows the Corrective Action Investigation (CAI) stage, which results in development of a set of contaminant boundary forecasts produced from groundwater flow and contaminant transport modeling of the Frenchman Flat CAU. The Frenchman Flat CAU is located in the southeastern portion of the NNSS and comprises 10 underground nuclear tests. The tests were conducted between 1965 and 1971 and resulted in the release of radionuclides in the subsurface in the vicinity of the test cavities. Two important aspects of the corrective action process are presented within this CADD/CAP. The CADD portion describes the results of the Frenchman Flatmore » CAU data-collection and modeling activities completed during the CAI stage. The corrective action objectives and the actions recommended to meet the objectives are also described. The CAP portion describes the corrective action implementation plan. The CAP begins with the presentation of CAU regulatory boundary objectives and initial use restriction boundaries that are identified and negotiated by NNSA/NSO and the Nevada Division of Environmental Protection (NDEP). The CAP also presents the model evaluation process designed to build confidence that the flow and contaminant transport modeling results can be used for the regulatory decisions required for CAU closure. The first two stages of the strategy have been completed for the Frenchman Flat CAU. A value of information analysis and a CAIP were developed during the CAIP stage. During the CAI stage, a CAIP addendum was developed, and the activities proposed in the CAIP and addendum were completed. These activities included hydrogeologic investigation of the underground testing areas, aquifer testing, isotopic and geochemistry-based investigations, and integrated geophysical investigations. After these investigations, a groundwater flow and contaminant transport model was developed to forecast contaminant boundaries that enclose areas potentially exceeding the Safe Drinking Water Act radiological standards at any time within 1,000 years. An external peer review of the groundwater flow and contaminant transport model was completed, and the model was accepted by NDEP to allow advancement to the CADD/CAP stage. The CADD/CAP stage focuses on model evaluation to ensure that existing models provide adequate guidance for the regulatory decisions regarding monitoring and institutional controls. Data-collection activities are identified and implemented to address key uncertainties in the flow and contaminant transport models. During the CR stage, final use restriction boundaries and CAU regulatory boundaries are negotiated and established; a long-term closure monitoring program is developed and implemented; and the approaches and policies for institutional controls are initiated. The model evaluation process described in this plan consists of an iterative series of five steps designed to build confidence in the site conceptual model and model forecasts. These steps are designed to identify data-collection activities (Step 1), document the data-collection activities in the 0CADD/CAP (Step 2), and perform the activities (Step 3). The new data are then assessed; the model is refined, if necessary; the modeling results are evaluated; and a model evaluation report is prepared (Step 4). The assessments are made by the modeling team and presented to the pre-emptive review committee. The decision is made by the modeling team with the assistance of the pre-emptive review committee and concurrence of NNSA/NSO to continue data and model assessment/refinement, recommend additional data collection, or recommend advancing to the CR stage. A recommendation to advance to the CR stage is based on whether the model is considered to be sufficiently reliable for designing a monitoring system and developing effective institutional controls. The decision to advance to the CR stage or to return to step 1 of the process is then made by NDEP (Step 5).« less

High-performance all-solid-state flexible supercapacitors based on two-step activated carbon cloth

NASA Astrophysics Data System (ADS)

Jiang, Shulan; Shi, Tielin; Zhan, Xiaobin; Long, Hu; Xi, Shuang; Hu, Hao; Tang, Zirong

2014-12-01

A simple and effective strategy is proposed to activate carbon cloth for the fabrication of flexible and high-performance supercapacitors. Firstly, the carbon cloth surface is exfoliated as nanotextures through wet chemical treatment, then an annealing process is applied at H2/N2 atmosphere to reduce the surface oxygen functional groups which are mainly introduced from the first step. The activated carbon cloth electrode shows excellent wettablity, large surface area and delivers remarkable electrochemical performance. A maximum areal capacitance of 485.64 mF cm-2 at the current density of 2 mA cm-2 is achieved for the activated carbon cloth electrode, which is considerably larger than the resported results for carbon cloth. Furthermore, the flexible all-solid-state supercapacitor, which is fabricated based on the activated carbon cloth electrodes, shows high areal capacitance, superior cycling stability as well as stable electrochemical performance even under constant bending or twisting conditions. An areal capacitance of 161.28 mF cm-2 is achieved at the current density of 12.5 mA cm-2, and 104% of its initial capacitance is retained after 30,000 charging/discharging cycles. This study would also provide an effective way to boost devices' electrochemical performance by accommodating other active materials on the activated carbon cloth.

Overview of Advanced Space Propulsion Activities in the Space Environmental Effects Team at MSFC

NASA Technical Reports Server (NTRS)

Edwards, David; Carruth, Ralph; Vaughn, Jason; Schneider, Todd; Kamenetzky, Rachel; Gray, Perry

2000-01-01

Exploration of our solar system, and beyond, requires spacecraft velocities beyond our current technological level. Technologies addressing this limitation are numerous. The Space Environmental Effects (SEE) Team at the Marshall Space Flight Center (MSFC) is focused on three discipline areas of advanced propulsion; Tethers, Beamed Energy, and Plasma. This presentation will give an overview of advanced propulsion related activities in the Space Environmental Effects Team at MSFC. Advancements in the application of tethers for spacecraft propulsion were made while developing the Propulsive Small Expendable Deployer System (ProSEDS). New tether materials were developed to meet the specifications of the ProSEDS mission and new techniques had to be developed to test and characterize these tethers. Plasma contactors were developed, tested and modified to meet new requirements. Follow-on activities in tether propulsion include the Air-SEDS activity. Beamed energy activities initiated with an experimental investigation to quantify the momentum transfer subsequent to high power, 5J, ablative laser interaction with materials. The next step with this experimental investigation is to quantify non-ablative photon momentum transfer. This step was started last year and will be used to characterize the efficiency of solar sail materials before and after exposure to Space Environmental Effects (SEE). Our focus with plasma, for propulsion, concentrates on optimizing energy deposition into a magnetically confined plasma and integration of measurement techniques for determining plasma parameters. Plasma confinement is accomplished with the Marshall Magnetic Mirror (M3) device. Initial energy coupling experiments will consist of injecting a 50 amp electron beam into a target plasma. Measurements of plasma temperature and density will be used to determine the effect of changes in magnetic field structure, beam current, and gas species. Experimental observations will be compared to predictions from computer modeling.

Exploring the Process of Implementing Healthy Workplace Initiatives: Mapping to Kotter's Leading Change Model.

PubMed

Chappell, Stacie; Pescud, Melanie; Waterworth, Pippa; Shilton, Trevor; Roche, Dee; Ledger, Melissa; Slevin, Terry; Rosenberg, Michael

2016-10-01

The aim of this study was to use Kotter's leading change model to explore the implementation of workplace health and wellbeing initiatives. Qualitative interviews were conducted with 31 workplace representatives with a healthy workplace initiative. None of the workplaces used a formal change management model when implementing their healthy workplace initiatives. Not all of the steps in Kotter model were considered necessary and the order of the steps was challenged. For example, interviewees perceived that communicating the vision, developing the vision, and creating a guiding coalition were integral parts of the process, although there was less emphasis on the importance of creating a sense of urgency and consolidating change. Although none of the workplaces reported using a formal organizational change model when implementing their healthy workplace initiatives, there did appear to be perceived merit in using the steps in Kotter's model.

Six-minute-walk distance and accelerometry predict outcomes in chronic obstructive pulmonary disease independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group.

PubMed

Durheim, Michael T; Smith, Patrick J; Babyak, Michael A; Mabe, Stephanie K; Martinu, Tereza; Welty-Wolf, Karen E; Emery, Charles F; Palmer, Scott M; Blumenthal, James A

2015-03-01

The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002). Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.

Alterations of rings B and C of colchicine are cumulative in overall binding to tubulin but modify each kinetic step.

PubMed

Dumortier, C; Gorbunoff, M J; Andreu, J M; Engelborghs, Y

1996-12-10

The role of the elimination of ring B and/or the modification of ring C of colchicine in tubulin binding kinetics and thermodynamics has been characterized, using four different molecules. These ligands are colchicine (COL); 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-on e (MTC), in which the central ring B has been reduced to one bond; allocolchicine (ALLO), in which ring C has been replaced by a six-membered ring; and 2,3,4-trimethoxy-4'-carbomethoxy-1,1'-biphenyl (TCB), where the same two modifications are made simultaneously. This paper describes the kinetics of association of ALLO with tubulin. The binding is accompanied by a fluorescence increase with slow biphasic kinetics, indicating binding to fast and slow tubulin isotypes. Binding to each of these isotypes occurs in two steps: a fast initial binding followed by a slower isomerization step. The K1 and k2 values for ALLO at 25 degrees C are 14,000 +/- 2,000 and 25,000 +/- 6,000 M-1 (fast and slow isotypes) and 0.055 +/- 0.003 s-1 and 0.013 +/- 0.001 s-1 (fast and slow isotype), respectively. For ALLO the reaction standard enthalpy change of the initial binding is 68 +/- 5 kJ.mol-1 (fast isotype) and 45 +/- 33 kJ.mol-1 (slow isotype) and the activation energy for the second forward step is 58 +/- 14 kJ.mol-1 (fast isotype) and 81 +/- 17 kJ.mol-1 (slow isotype). Displacement kinetics of bound ALLO by podophyllotoxin was monoexponential. The activation energy for the isomerization in the off direction is 107 +/- 7 kJ.mol-1. Comparison of the thermodynamic parameters for all four compounds shows that the modifications of both rings are cumulative with respect to overall binding. For the intermediate state there is a mutual influence of both modifications, suggesting an alteration of the reaction pathway.

A method for the inclusion of physical activity-related health benefits in cost-benefit analysis of built environment initiatives.

PubMed

Zapata-Diomedi, Belen; Gunn, Lucy; Giles-Corti, Billie; Shiell, Alan; Lennert Veerman, J

2018-01-01

The built environment has a significant influence on population levels of physical activity (PA) and therefore health. However, PA-related health benefits are seldom considered in transport and urban planning (i.e. built environment interventions) cost-benefit analysis. Cost-benefit analysis implies that the benefits of any initiative are valued in monetary terms to make them commensurable with costs. This leads to the need for monetised values of the health benefits of PA. The aim of this study was to explore a method for the incorporation of monetised PA-related health benefits in cost-benefit analysis of built environment interventions. Firstly, we estimated the change in population level of PA attributable to a change in the built environment due to the intervention. Then, changes in population levels of PA were translated into monetary values. For the first step we used estimates from the literature for the association of built environment features with physical activity outcomes. For the second step we used the multi-cohort proportional multi-state life table model to predict changes in health-adjusted life years and health care costs as a function of changes in PA. Finally, we monetised health-adjusted life years using the value of a statistical life year. Future research could adapt these methods to assess the health and economic impacts of specific urban development scenarios by working in collaboration with urban planners. Copyright © 2017 Elsevier Inc. All rights reserved.

Short bowel mucosal morphology, proliferation and inflammation at first and repeat STEP procedures.

PubMed

Mutanen, Annika; Barrett, Meredith; Feng, Yongjia; Lohi, Jouko; Rabah, Raja; Teitelbaum, Daniel H; Pakarinen, Mikko P

2018-04-17

Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7-3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p=0.05), while enteral caloric intake increased from 6% to 36% (p=0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p=0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p>0.05 for all). Patients, who required repeat STEP tended to be younger (p=0.057) with less apoptotic crypt cells (p=0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (p<0.05 for both). No adaptive mucosal hyperplasia or muscular alterations occurred between first and repeat STEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level IV, retrospective study. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulated Eukaryotic DNA Replication Origin Firing with Purified Proteins

PubMed Central

Yeeles, Joseph T.P.; Deegan, Tom D.; Janska, Agnieszka; Early, Anne; Diffley, John F. X.

2016-01-01

Eukaryotic cells initiate DNA replication from multiple origins, which must be tightly regulated to promote precise genome duplication in every cell cycle. To accomplish this, initiation is partitioned into two temporally discrete steps: a double hexameric MCM complex is first loaded at replication origins during G1 phase, and then converted to the active CMG (Cdc45, MCM, GINS) helicase during S phase. Here we describe the reconstitution of budding yeast DNA replication initiation with 16 purified replication factors, made from 42 polypeptides. Origin-dependent initiation recapitulates regulation seen in vivo. Cyclin dependent kinase (CDK) inhibits MCM loading by phosphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2 and Sld3. Dbf4 dependent kinase (DDK) promotes replication by phosphorylating MCM, and can act either before or after CDK. These experiments define the minimum complement of proteins, protein kinase substrates and co-factors required for regulated eukaryotic DNA replication. PMID:25739503

Regulated eukaryotic DNA replication origin firing with purified proteins.

PubMed

Yeeles, Joseph T P; Deegan, Tom D; Janska, Agnieszka; Early, Anne; Diffley, John F X

2015-03-26

Eukaryotic cells initiate DNA replication from multiple origins, which must be tightly regulated to promote precise genome duplication in every cell cycle. To accomplish this, initiation is partitioned into two temporally discrete steps: a double hexameric minichromosome maintenance (MCM) complex is first loaded at replication origins during G1 phase, and then converted to the active CMG (Cdc45-MCM-GINS) helicase during S phase. Here we describe the reconstitution of budding yeast DNA replication initiation with 16 purified replication factors, made from 42 polypeptides. Origin-dependent initiation recapitulates regulation seen in vivo. Cyclin-dependent kinase (CDK) inhibits MCM loading by phosphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2 and Sld3. Dbf4-dependent kinase (DDK) promotes replication by phosphorylating MCM, and can act either before or after CDK. These experiments define the minimum complement of proteins, protein kinase substrates and co-factors required for regulated eukaryotic DNA replication.

Secretory immunoglobulin purification from whey by chromatographic techniques.

PubMed

Matlschweiger, Alexander; Engelmaier, Hannah; Himmler, Gottfried; Hahn, Rainer

2017-08-15

Secretory immunoglobulins (SIg) are a major fraction of the mucosal immune system and represent potential drug candidates. So far, platform technologies for their purification do not exist. SIg from animal whey was used as a model to develop a simple, efficient and potentially generic chromatographic purification process. Several chromatographic stationary phases were tested. A combination of two anion-exchange steps resulted in the highest purity. The key step was the use of a small-porous anion exchanger operated in flow-through mode. Diffusion of SIg into the resin particles was significantly hindered, while the main impurities, IgG and serum albumin, were bound. In this step, initial purity was increased from 66% to 89% with a step yield of 88%. In a second anion-exchange step using giga-porous material, SIg was captured and purified by step or linear gradient elution to obtain fractions with purities >95%. For the step gradient elution step yield of highly pure SIg was 54%. Elution of SIgA and SIgM with a linear gradient resulted in a step yield of 56% and 35%, respectively. Overall yields for both anion exchange steps were 43% for the combination of flow-through and step elution mode. Combination of flow-through and linear gradient elution mode resulted in a yield of 44% for SIgA and 39% for SIgM. The proposed process allows the purification of biologically active SIg from animal whey in preparative scale. For future applications, the process can easily be adopted for purification of recombinant secretory immunoglobulin species. Copyright © 2017 Elsevier B.V. All rights reserved.

On the Transition from Initial Leader to Stepped Leader in Negative Cloud-to-ground Lightning

NASA Astrophysics Data System (ADS)

Stolzenburg, M.; Marshall, T. C.; Karunarathne, S.; Orville, R. E.

2017-12-01

High-speed video and electric field change (E-change) data are used to describe the first 5 ms of a natural negative cloud-to-ground (CG) flash. These observations reveal differences in appearance of both the video luminosity and the E-change pulses before the leader transitions to propagating as a negative stepped leader (SL). During the initial breakdown (IB) stage, the initial leader advances intermittently forward in jumps of 78-175 m, at intervals of 100-280 μs, and in separate bursts that are bright for a few 20-μs video frames. The IB pulses accompanying these luminosity bursts have long duration, large amplitude, and a characteristic bipolar shape in nearby E-change observations. In the time between IB pulses, the initial leader is very dim or not visible during the earliest 1-2 ms of the IB stage. Over the next few milliseconds, the leader propagation transitions to an early SL phase, in which the leader tips advance 20-59 m forward at more regular intervals of 40-80 μs during relatively dim and brief steps. In the E-change data, the accompanying SL pulses have very short duration, small amplitude, and are typically unipolar. These data indicate that when the entire initial leader length behind the lower end begins to remain illuminated between bursts, the propagation mode changes from IB bursts to SL steps, and the IB stage ends. Additional differences in initial leader character are evident during the return stroke, as its luminosity speed decreases sharply upon reaching the topmost initial leader section of the channel, and that section of channel does not saturate the video intensity. Results of these analyses support a prior hypothesis that the early initial leader development occurs in the absence of a continuously hot channel, and consequently, the initial leader propagation is unlike the self-propagating advance of the later stepped leader.

Comparison of enamel bond fatigue durability of universal adhesives and two-step self-etch adhesives in self-etch mode.

PubMed

Tsujimoto, Akimasa; Barkmeier, Wayne W; Hosoya, Yumiko; Nojiri, Kie; Nagura, Yuko; Takamizawa, Toshiki; Latta, Mark A; Miyazaki, Masashi

2017-10-01

To comparatively evaluate universal adhesives and two-step self-etch adhesives for enamel bond fatigue durability in self-etch mode. Three universal adhesives (Clearfil Universal Bond; G-Premio Bond; Scotchbond Universal Adhesive) and three two-step self-etch adhesives (Clearfil SE Bond; Clearfil SE Bond 2; OptiBond XTR) were used. The initial shear bond strength and shear fatigue strength of the adhesive to enamel in self-etch mode were determined. The initial shear bond strengths of the universal adhesives to enamel in self-etch mode was significantly lower than those of two-step self-etch adhesives and initial shear bond strengths were not influenced by type of adhesive in each adhesive category. The shear fatigue strengths of universal adhesives to enamel in self-etch mode were significantly lower than that of Clearfil SE Bond and Clearfil SE Bond 2, but similar to that OptiBond XTR. Unlike two-step self-etch adhesives, the initial shear bond strength and shear fatigue strength of universal adhesives to enamel in self-etch mode was not influenced by the type of adhesive. This laboratory study showed that the enamel bond fatigue durability of universal adhesives was lower than Clearfil SE Bond and Clearfil SE Bond 2, similar to Optibond XTR, and was not influenced by type of adhesive, unlike two-step self-etch adhesives.

Central vein perforation during tunneled dialysis catheter insertion: principles of acute management.

PubMed

Pua, Uei

2014-10-01

Central venous perforation during dialysis catheter insertion is a potentially fatal complication. Prompt recognition and judicious initial steps are important in optimizing the outcome. The purpose of this manuscript is to illustrate the imaging features and steps in initial management. © 2014 International Society for Hemodialysis.

Using Mixed Methods to Assess Initiatives with Broad-Based Goals

ERIC Educational Resources Information Center

Inkelas, Karen Kurotsuchi

2017-01-01

This chapter describes a process for assessing programmatic initiatives with broad-ranging goals with the use of a mixed-methods design. Using an example of a day-long teaching development conference, this chapter provides practitioners step-by-step guidance on how to implement this assessment process.

Physical activity and sedentary behaviors in postpartum Latinas: Madres para la Salud.

PubMed

Ainsworth, Barbara E; Keller, Colleen; Herrmann, Stephen; Belyea, Michael; Records, Kathryn; Nagle-Williams, Allison; Vega-López, Sonia; Permana, Paska; Coonrod, Dean V

2013-07-01

To describe the physical activity (PA) and sedentary behaviors of postpartum Latinas who are overweight or obese before initiating Madres para la Salud, a social support-mediated walking intervention to promote postpartum weight loss. One hundred thirty-nine postpartum women (13.6 ± 7.7 wk since childbirth, age = 28.3 ± 5.6 yr, BMI = 29.7 ± 3.5 kg · m(-2); mean ± SD), recruited from organizations serving Latino residents in the Phoenix, Arizona, area completed the Stanford Brief Activity Survey and concurrently wore an accelerometer (ActiGraph) and a pedometer for 7 d and kept a PA record. Most were classified as inactive and lightly active on the Stanford Brief Activity Survey (51% inactive, 37% light, 11% moderate). Most time was spent in sedentary (512.0 ± 169.9 min · d(-1)) and light-intensity PA (242.4 ± 51.4 min · d(-1)) with less time in moderate-intensity lifestyle (78.3 ± 39.9 min · d(-1)), moderate-intensity walking (16.6 ± 14.4 min · d(-1)), and vigorous-intensity PA (0.34 ± 1.5 min · d(-1)). Pedometer steps per day were low (total = 4973 ± 2202 steps, aerobic = 412 ± 774 steps), with most participants rated as sedentary (61%) or low active (28.1%). Consistent with objective PA measures, PA records showed more time spent in light-intensity PA such as home care, cooking, child care and self-care tasks, occupation, religious events, and watching television. By and large, the postpartum Latinas enrolled spent most of their day in low-intensity activity levels with little time spent in health-enhancing PA levels/behaviors. This demographic should be the focus of PA interventions to increase PA to health-enhancing levels.

Automatic initial and final segmentation in cleft palate speech of Mandarin speakers

PubMed Central

Liu, Yin; Yin, Heng; Zhang, Junpeng; Zhang, Jing; Zhang, Jiang

2017-01-01

The speech unit segmentation is an important pre-processing step in the analysis of cleft palate speech. In Mandarin, one syllable is composed of two parts: initial and final. In cleft palate speech, the resonance disorders occur at the finals and the voiced initials, while the articulation disorders occur at the unvoiced initials. Thus, the initials and finals are the minimum speech units, which could reflect the characteristics of cleft palate speech disorders. In this work, an automatic initial/final segmentation method is proposed. It is an important preprocessing step in cleft palate speech signal processing. The tested cleft palate speech utterances are collected from the Cleft Palate Speech Treatment Center in the Hospital of Stomatology, Sichuan University, which has the largest cleft palate patients in China. The cleft palate speech data includes 824 speech segments, and the control samples contain 228 speech segments. The syllables are extracted from the speech utterances firstly. The proposed syllable extraction method avoids the training stage, and achieves a good performance for both voiced and unvoiced speech. Then, the syllables are classified into with “quasi-unvoiced” or with “quasi-voiced” initials. Respective initial/final segmentation methods are proposed to these two types of syllables. Moreover, a two-step segmentation method is proposed. The rough locations of syllable and initial/final boundaries are refined in the second segmentation step, in order to improve the robustness of segmentation accuracy. The experiments show that the initial/final segmentation accuracies for syllables with quasi-unvoiced initials are higher than quasi-voiced initials. For the cleft palate speech, the mean time error is 4.4ms for syllables with quasi-unvoiced initials, and 25.7ms for syllables with quasi-voiced initials, and the correct segmentation accuracy P30 for all the syllables is 91.69%. For the control samples, P30 for all the syllables is 91.24%. PMID:28926572

Automatic initial and final segmentation in cleft palate speech of Mandarin speakers.

PubMed

He, Ling; Liu, Yin; Yin, Heng; Zhang, Junpeng; Zhang, Jing; Zhang, Jiang

2017-01-01

The speech unit segmentation is an important pre-processing step in the analysis of cleft palate speech. In Mandarin, one syllable is composed of two parts: initial and final. In cleft palate speech, the resonance disorders occur at the finals and the voiced initials, while the articulation disorders occur at the unvoiced initials. Thus, the initials and finals are the minimum speech units, which could reflect the characteristics of cleft palate speech disorders. In this work, an automatic initial/final segmentation method is proposed. It is an important preprocessing step in cleft palate speech signal processing. The tested cleft palate speech utterances are collected from the Cleft Palate Speech Treatment Center in the Hospital of Stomatology, Sichuan University, which has the largest cleft palate patients in China. The cleft palate speech data includes 824 speech segments, and the control samples contain 228 speech segments. The syllables are extracted from the speech utterances firstly. The proposed syllable extraction method avoids the training stage, and achieves a good performance for both voiced and unvoiced speech. Then, the syllables are classified into with "quasi-unvoiced" or with "quasi-voiced" initials. Respective initial/final segmentation methods are proposed to these two types of syllables. Moreover, a two-step segmentation method is proposed. The rough locations of syllable and initial/final boundaries are refined in the second segmentation step, in order to improve the robustness of segmentation accuracy. The experiments show that the initial/final segmentation accuracies for syllables with quasi-unvoiced initials are higher than quasi-voiced initials. For the cleft palate speech, the mean time error is 4.4ms for syllables with quasi-unvoiced initials, and 25.7ms for syllables with quasi-voiced initials, and the correct segmentation accuracy P30 for all the syllables is 91.69%. For the control samples, P30 for all the syllables is 91.24%.

When a Step Is Not a Step! Specificity Analysis of Five Physical Activity Monitors.

PubMed

O'Connell, Sandra; ÓLaighin, Gearóid; Quinlan, Leo R

2017-01-01

Physical activity is an essential aspect of a healthy lifestyle for both physical and mental health states. As step count is one of the most utilized measures for quantifying physical activity it is important that activity-monitoring devices be both sensitive and specific in recording actual steps taken and disregard non-stepping body movements. The objective of this study was to assess the specificity of five activity monitors during a variety of prescribed non-stepping activities. Participants wore five activity monitors simultaneously for a variety of prescribed activities including deskwork, taking an elevator, taking a bus journey, automobile driving, washing and drying dishes; functional reaching task; indoor cycling; outdoor cycling; and indoor rowing. Each task was carried out for either a specific duration of time or over a specific distance. Activity monitors tested were the ActivPAL micro™, NL-2000™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2)™, Fitbit One™ and Jawbone UP™. Participants were video-recorded while carrying out the prescribed activities and the false positive step count registered on each activity monitor was obtained and compared to the video. All activity monitors registered a significant number of false positive steps per minute during one or more of the prescribed activities. The Withings™ activity performed best, registering a significant number of false positive steps per minute during the outdoor cycling activity only (P = 0.025). The Jawbone™ registered a significant number of false positive steps during the functional reaching task and while washing and drying dishes, which involved arm and hand movement (P < 0.01 for both). The ActivPAL™ registered a significant number of false positive steps during the cycling exercises (P < 0.001 for both). As a number of false positive steps were registered on the activity monitors during the non-stepping activities, the authors conclude that non-stepping physical activities can result in the false detection of steps. This can negatively affect the quantification of physical activity with regard to step count as an output. The Withings™ activity monitor performed best with regard to specificity during the activities of daily living tested.

Nasa's Emerging Productivity Program

NASA Technical Reports Server (NTRS)

Braunstein, D. R.

1984-01-01

The goals, membership, and organizational structure of the NASA Productivity Steering Committee are described as well as steps taken to make NASA a leader in the development and application of productivity and quality concepts at every level of agency management. The overall strategy for the Productivity Improvement and Quality Enhancement (PIQE) Program is through employee involvement, both civil servant and contractor, in all phases of agency-wide activity. Elements of the PIQE program and initial thrusts are examined.

Phosphorylation of a Tyrosine Residue on Zap70 by Lck and Its Subsequent Binding via an SH2 Domain May Be a Key Gatekeeper of T Cell Receptor Signaling In Vivo.

PubMed

Thill, Peter A; Weiss, Arthur; Chakraborty, Arup K

2016-09-15

The initiation of signaling in T lymphocytes in response to the binding of the T cell receptor (TCR) to cognate ligands is a key step in the emergence of adaptive immune responses. Conventional models posit that TCR signaling is initiated by the phosphorylation of receptor-associated immune receptor activation motifs (ITAMs). The cytoplasmic tyrosine kinase Zap70 binds to phosphorylated ITAMs, is subsequently activated, and then propagates downstream signaling. While evidence for such models is provided by experiments with cell lines, in vivo, Zap70 is bound to phosphorylated ITAMs in resting T cells. However, Zap70 is activated only upon TCR binding to cognate ligand. We report the results of computational studies of a new model for the initiation of TCR signaling that incorporates these in vivo observations. Importantly, the new model is shown to allow better and faster TCR discrimination between self-ligands and foreign ligands. The new model is consistent with many past experimental observations, and experiments that could further test the model are proposed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Introducing the pro-coagulant contact system in the numerical assessment of device-related thrombosis.

PubMed

Méndez Rojano, Rodrigo; Mendez, Simon; Nicoud, Franck

2018-06-01

Thrombosis is a major concern in blood-coated medical devices. Contact activation, which is the initial part of the coagulation cascade in device-related thrombosis, is not considered in current thrombus formation models. In the present study, pro-coagulant reactions including the contact activation system are coupled with a fluid solver in order to evaluate the potential of the contact system to initiate thrombin production. The biochemical/fluid model is applied to a backward-facing step configuration, a flow configuration that frequently appears in medical devices. In contrast to the in vivo thrombosis models in which a specific thrombotic zone (injury region) is set a priori by the user to initiate the coagulation reaction, a reactive surface boundary condition is applied to the whole device wall. Simulation results show large thrombin concentration in regions related to recirculation zones without the need of an a priori knowledge of the thrombus location. The numerical results align well with the regions prone to thrombosis observed in experimental results reported in the literature. This approach could complement thrombus formation models that take into account platelet activity and thrombus growth to optimize a wide range of medical devices.

Step-Initiation Deficits in Children with Faulty Posture Diagnosed with Neurodevelopmental Disorders during Infancy.

PubMed

Stania, Magdalena; Sarat-Spek, Alina; Blacha, Teresa; Kazek, Beata; Słomka, Kajetan J; Emich-Widera, Ewa; Juras, Grzegorz

2017-01-01

Early detection of movement deficits during step initiation will facilitate the selection of the optimal physiotherapy management strategy. The main aim of the study was to assess potential differences in step initiation between 5- and 6-year-old children with faulty posture who had been diagnosed with neurodevelopmental disorders during infancy and healthy children. The experimental group consisted of 19 children aged 5-6 years with faulty posture, who had been diagnosed with neurodevelopmental disorders during infancy and were given physiotherapy in the first year of their lives. The control group comprised 19 nursery school children aged 5-6 years with no postural defects, no history of postural control or movement deficits, and no physiotherapy interventions in the first year of their lives. Step initiation was performed on force platforms under various conditions, i.e., with and without an obstacle, stepping up onto a platform placed at a higher level, stepping down onto a platform placed on a lower level. The recording of center of foot pressure (COP) displacements was divided into three phases: phase 1 (P1)-quiet standing before step initiation, phase 2 (P2)-transit, phase 3 (P3)-quiet standing until measurement completion. The Tukey post hoc test showed that the means of sway range (raCOP) and mean velocity (vCOP) in sagittal ( AP ) plane for phase 1 and vCOP in frontal ( ML ) plane for phase 3 registered in the step-up trial were significantly higher ( p  < 0.05) in children with faulty posture compared to children with typical development. P1vCOP ML , P3vCOP AP , P3raCOP ML , and P3vCOP ML of the step-down trial were also significantly higher in children with faulty posture ( p  < 0.05). Inclusion of functional movement exercises (stair-walking tasks) in physiotherapy interventions for children with postural defects seems well justified.The trial was registered in the Australian and New Zealand Clinical Trials Registry (no. ACTRN12617001068358).

Gynecomastia: pathophysiology, evaluation, and management.

PubMed

Johnson, Ruth E; Murad, M Hassan

2009-11-01

Gynecomastia, defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications. Although a fairly common presentation in the primary care setting and mostly of benign etiology, it can cause patients considerable anxiety. The initial step is to rule out pseudogynecomastia by careful history taking and physical examination. A stepwise approach that includes imaging and laboratory testing to exclude neoplasms and endocrinopathies may facilitate cost-effective diagnosis. If results of all studies are normal, idiopathic gynecomastia is diagnosed. The evidence in this area is mainly of observational nature and lower quality.

Free energy landscape of electrocatalytic CO2 reduction to CO on aqueous FeN4 center embedded graphene studied by ab initio molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sheng, Tian; Sun, Shi-Gang

2017-11-01

Experiments have found that the porphyrin-like FeN4 site in Fe-N-C materials is highly efficient for the electrochemical reduction of CO2 into CO. In this work, we investigated the reduction mechanisms on FeN4 embedded graphene layer catalyst with some explicit water molecules by combining the constrained ab initio molecular dynamics simulations and thermodynamic integrations. The reaction free energy and electron transfer in each elementary step were identified. The initial CO2 activation was identified to go through the first electron transfer to form adsorbed CO2- anion and the CO desorption was the rate limiting step in the overall catalytic cycle.

Memory processes during sleep: beyond the standard consolidation theory.

PubMed

Axmacher, Nikolai; Draguhn, Andreas; Elger, Christian E; Fell, Juergen

2009-07-01

Two-step theories of memory formation suggest that an initial encoding stage, during which transient neural assemblies are formed in the hippocampus, is followed by a second step called consolidation, which involves re-processing of activity patterns and is associated with an increasing involvement of the neocortex. Several studies in human subjects as well as in animals suggest that memory consolidation occurs predominantly during sleep (standard consolidation model). Alternatively, it has been suggested that consolidation may occur during waking state as well and that the role of sleep is rather to restore encoding capabilities of synaptic connections (synaptic downscaling theory). Here, we review the experimental evidence favoring and challenging these two views and suggest an integrative model of memory consolidation.

Long-term efficiency of soil stabilization with apatite and Slovakite: the impact of two earthworm species (Lumbricus terrestris and Dendrobaena veneta) on lead bioaccessibility and soil functioning.

PubMed

Tica, D; Udovic, M; Lestan, D

2013-03-01

Remediation soil is exposed to various environmental factors over time that can affect the final success of the operation. In the present study, we assessed Pb bioaccessibility and microbial activity in industrially polluted soil (Arnoldstein, Austria) stabilized with 5% (w/w) of Slovakite and 5% (w/w) of apatite soil after exposure to two earthworm species, Lumbricus terrestris and Dendrobaena veneta, used as model environmental biotic soil factors. Stabilization resulted in reduced Pb bioaccessibility, as assessed with one-step extraction tests and six-step sequential extraction, and improved soil functioning, mirrored in reduced β-glucosidase activity in soil. Both earthworm species increased Pb bioaccessibility, thus decreasing the initial stabilization efficacy and indicating the importance of considering the long-term fate of remediated soil. The earthworm species had different effects on soil enzyme activity, which can be attributed to species-specific microbial populations in earthworm gut acting on the ingested soil. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maintaining High Ambulatory Activity Levels of Sedentary Adults with a Reinforcement Thinning Schedule

PubMed Central

Andrade, Leonardo F.; Barry, Danielle; Litt, Mark D.; Petry, Nancy M.

2016-01-01

Physical inactivity is a leading cause of mortality. Reinforcement interventions appear useful for increasing activity and preventing adverse consequences of sedentary lifestyles. This study evaluated a reinforcement thinning schedule for maintaining high activity levels. Sedentary adults (n=77) were given pedometers and encouraged to walk ≥10,000 steps/day. Initially, all participants earned rewards for each day they walked ≥10,000 steps. Subsequently, 61 participants were randomized to a monitoring only condition or a monitoring plus reinforcement thinning condition, in which frequencies of monitoring and reinforcing walking decreased over 12 weeks. The mean ± SD percentage of participants in the monitoring plusreinforcement thinning condition who met walking goals was 83% ± 24% versus. 55% ± 31% for participants in the monitoring only condition, p < .001. Thus, this monitoring plusreinforcement thinning schedule maintained high rates of walking when it was in effect; however, groups did not differ at a 24-week follow-up. Monitoring plus reinforcement thinning schedules, nevertheless, hold potential to extend benefits of reinforcement interventions at low costs. PMID:25041789

Membrane-Induced Structural Rearrangement and Identification of a Novel Membrane Anchor in Talin F2F3

PubMed Central

Arcario, Mark J.; Tajkhorshid, Emad

2014-01-01

Experimental challenges associated with characterization of the membrane-bound form of talin have prevented us from understanding the molecular mechanism of its membrane-dependent integrin activation. Here, utilizing what we believe to be a novel membrane mimetic model, we present a reproducible model of membrane-bound talin observed across multiple independent simulations. We characterize both local and global membrane-induced structural transitions that successfully reconcile discrepancies between biochemical and structural studies and provide insight into how talin might modulate integrin function. Membrane binding of talin, captured in unbiased simulations, proceeds through three distinct steps: initial electrostatic recruitment of the F2 subdomain to anionic lipids via several basic residues; insertion of an initially buried, conserved hydrophobic anchor into the membrane; and association of the F3 subdomain with the membrane surface through a large, interdomain conformational change. These latter two steps, to our knowledge, have not been observed or described previously. Electrostatic analysis shows talin F2F3 to be highly polarized, with a highly positive underside, which we attribute to the initial electrostatic recruitment, and a negative top face, which can help orient the protein optimally with respect to the membrane, thereby reducing the number of unproductive membrane collision events. PMID:25418091

TOMO3D: 3-D joint refraction and reflection traveltime tomography parallel code for active-source seismic data—synthetic test

NASA Astrophysics Data System (ADS)

Meléndez, A.; Korenaga, J.; Sallarès, V.; Miniussi, A.; Ranero, C. R.

2015-10-01

We present a new 3-D traveltime tomography code (TOMO3D) for the modelling of active-source seismic data that uses the arrival times of both refracted and reflected seismic phases to derive the velocity distribution and the geometry of reflecting boundaries in the subsurface. This code is based on its popular 2-D version TOMO2D from which it inherited the methods to solve the forward and inverse problems. The traveltime calculations are done using a hybrid ray-tracing technique combining the graph and bending methods. The LSQR algorithm is used to perform the iterative regularized inversion to improve the initial velocity and depth models. In order to cope with an increased computational demand due to the incorporation of the third dimension, the forward problem solver, which takes most of the run time (˜90 per cent in the test presented here), has been parallelized with a combination of multi-processing and message passing interface standards. This parallelization distributes the ray-tracing and traveltime calculations among available computational resources. The code's performance is illustrated with a realistic synthetic example, including a checkerboard anomaly and two reflectors, which simulates the geometry of a subduction zone. The code is designed to invert for a single reflector at a time. A data-driven layer-stripping strategy is proposed for cases involving multiple reflectors, and it is tested for the successive inversion of the two reflectors. Layers are bound by consecutive reflectors, and an initial velocity model for each inversion step incorporates the results from previous steps. This strategy poses simpler inversion problems at each step, allowing the recovery of strong velocity discontinuities that would otherwise be smoothened.

Temperature induced decoupling of enzymatic hydrolysis and carbon remineralization in long-term incubations of Arctic and temperate sediments

NASA Astrophysics Data System (ADS)

Robador, Alberto; Brüchert, Volker; Steen, Andrew D.; Arnosti, Carol

2010-04-01

Extracellular enzymatic hydrolysis of high-molecular weight organic matter is the initial step in sedimentary organic carbon degradation and is often regarded as the rate-limiting step. Temperature effects on enzyme activities may therefore exert an indirect control on carbon mineralization. We explored the temperature sensitivity of enzymatic hydrolysis and its connection to subsequent steps in anoxic organic carbon degradation in long-term incubations of sediments from the Arctic and the North Sea. These sediments were incubated under anaerobic conditions for 24 months at temperatures of 0, 10, and 20 °C. The short-term temperature response of the active microbial community was tested in temperature gradient block incubations. The temperature optimum of extracellular enzymatic hydrolysis, as measured with a polysaccharide (chondroitin sulfate), differed between Arctic and temperate habitats by about 8-13 °C in fresh sediments and in sediments incubated for 24 months. In both Arctic and temperate sediments, the temperature response of chondroitin sulfate hydrolysis was initially similar to that of sulfate reduction. After 24 months, however, hydrolysis outpaced sulfate reduction rates, as demonstrated by increased concentrations of dissolved organic carbon (DOC) and total dissolved carbohydrates. This effect was stronger at higher incubation temperatures, particularly in the Arctic sediments. In all experiments, concentrations of volatile fatty acids (VFA) were low, indicating tight coupling between VFA production and consumption. Together, these data indicate that long-term incubation at elevated temperatures led to increased decoupling of hydrolytic DOC production relative to fermentation. Temperature increases in marine sedimentary environments may thus significantly affect the downstream carbon mineralization and lead to the increased formation of refractory DOC.

Canada's Deep Geological Repository For Used Nuclear Fuel -The Geoscientific Site Evaluation Process

NASA Astrophysics Data System (ADS)

Hirschorn, S.; Ben Belfadhel, M.; Blyth, A.; DesRoches, A. J.; McKelvie, J. R. M.; Parmenter, A.; Sanchez-Rico Castejon, M.; Urrutia-Bustos, A.; Vorauer, A.

2014-12-01

The Nuclear Waste Management Organization (NWMO) is responsible for implementing Adaptive Phased Management, the approach selected by the Government of Canada for long-term management of used nuclear fuel generated by Canadian nuclear reactors. In May 2010, the NWMO published and initiated a nine-step site selection process to find an informed and willing community to host a deep geological repository for Canada's used nuclear fuel. The site selection process is designed to address a broad range of technical and social, economic and cultural factors. The suitability of candidate areas will be assessed in a stepwise manner over a period of many years and include three main steps: Initial Screenings; Preliminary Assessments; and Detailed Site Characterizations. The Preliminary Assessment is conducted in two phases. NWMO has completed Phase 1 preliminary assessments for the first eight communities that entered into this step. While the Phase 1 desktop geoscientific assessments showed that each of the eight communities contains general areas that have the potential to satisfy the geoscientific safety requirements for hosting a deep geological repository, the assessment identified varying degrees of geoscientific complexity and uncertainty between communities, reflecting their different geological settings and structural histories. Phase 2 activities will include a sequence of high-resolution airborne geophysical surveys and focused geological field mapping to ground-truth lithology and structural features, followed by limited deep borehole drilling and testing. These activities will further evaluate the site's ability to meet the safety functions that a site would need to ultimately satisfy in order to be considered suitable. This paper provides an update on the site evaluation process and describes the approach, methods and criteria that are being used to conduct the geoscientific Preliminary Assessments.

Structural Controls of Neal Hot Springs Geothermal Field, Malhuer County, Oregon

NASA Astrophysics Data System (ADS)

Edwards, J. H.; Faulds, J. E.

2012-12-01

Detailed mapping (1:24,000) of the Neal Hot Springs area (90 km2) in eastern Oregon is part of a larger study of geothermal systems in the Basin and Range, which focuses on the structural controls of geothermal activity. The study area lies within the intersection of two regional grabens, the middle-late Miocene, N-striking, Oregon-Idaho graben and younger late Miocene to Holocene, NW-striking, western Snake River Plain graben. The geothermal field is marked by Neal Hot Springs, which effuse from opaline sinter mounds just north of Bully Creek. Wells producing geothermal fluids, with temperatures at 138°C, intersect a major, W-dipping, NNW-striking, high-angle normal fault at depths of 850-915 m. Displacement along this structure dies southward, with likely horse-tailing, which commonly produces high fracture density and a zone of high permeability conducive for channeling hydrothermal fluids. Mapping reveals that the geothermal resource lies within a local, left step-over. 'Hard-linkage' between strands of the left-stepping normal fault, revealed through a study of well chips and well logs, occurs through two concealed structures. Both are W-striking faults, with one that runs parallel to Cottonwood Creek and one 0.5 km N of the creek. Injection wells intersect these two transverse structures within the step-over. Stepping and displacement continue to the NW of the known geothermal field, along W-dipping, N-striking faults that cut lower to middle Miocene Hog Creek Formation, consisting of silicic and mafic volcanic rocks. These N-striking faults were likely initiated during initial Oregon-Idaho graben subsidence (15.3-15.1 Ma), with continued development through late Miocene. Bully Creek Formation deposits, middle to upper Miocene lacustrine and pyroclastic rocks, concomitantly filled the sub half-grabens, and they dip gently to moderately eastward. Younger, western Snake River Plain deposits, upper Miocene to Pliocene fluvial, lacustrine, and pyroclastic rocks, show various dip directions and gentle tilting. Extensive alluvial fan cover hinders collection of fault kinematic data, which coupled with limited regional seismicity, precludes careful calculation of local stress field orientations. However, the proximity of Neal (4 km) to the active, N- to NW-striking, oblique-normal slip Cottonwood Mountain fault and active hot springs (~90°C), opaline sinter mounds, and geothermal fluid flow at Neal suggest that the geothermal field lies within a reactived (Quaternary), southward-terminating, left-stepping, fault zone, which probably accommodates oblique-slip with a dominant normal component. Sugarloaf Butte (completely silicified and replaced) lies within a left step of this fault zone, ~5 km of Neal Hot Springs and is possibly related to the evolution of the geothermal system. Epithermal deposits and argillic to propylitic alteration in other nearby areas (e.g., Hope Butte, ~3 Ma, 5 km N) indicate previous geothermal activity.

Accuracy of 2 activity monitors in detecting steps in people with stroke and traumatic brain injury.

PubMed

Fulk, George D; Combs, Stephanie A; Danks, Kelly A; Nirider, Coby D; Raja, Bhavana; Reisman, Darcy S

2014-02-01

Advances in sensor technologies and signal processing techniques provide a method to accurately measure walking activity in the home and community. Activity monitors geared toward consumer or patient use may be an alternative to more expensive monitors designed for research to measure stepping activity. The objective of this study was to examine the accuracy of 2 consumer/patient activity monitors, the Fitbit Ultra and the Nike+ Fuelband, in identifying stepping activity in people with stroke and traumatic brain injury (TBI). Secondarily, the study sought to compare the accuracy of these 2 activity monitors with that of the StepWatch Activity Monitor (SAM) and a pedometer, the Yamax Digi-Walker SW-701 pedometer (YDWP). A cross-sectional design was used for this study. People with chronic stroke and TBI wore the 4 activity monitors while they performed the Two-Minute Walk Test (2MWT), during which they were videotaped. Activity monitor estimated steps taken were compared with actual steps taken counted from videotape. Accuracy and agreement between activity monitor estimated steps and actual steps were examined using intraclass correlation coefficients (ICC [2,1]) and the Bland-Altman method. The SAM demonstrated the greatest accuracy (ICC [2,1]=.97, mean difference between actual steps and SAM estimated steps=4.7 steps) followed by the Fitbit Ultra (ICC [2,1]=.73, mean difference between actual steps and Fitbit Ultra estimated steps=-9.7 steps), the YDWP (ICC [2,1]=.42, mean difference between actual steps and YDWP estimated steps=-28.8 steps), and the Nike+ Fuelband (ICC [2,1]=.20, mean difference between actual steps and Nike+ Fuelband estimated steps=-66.2 steps). Walking activity was measured over a short distance in a closed environment, and participants were high functioning ambulators, with a mean gait speed of 0.93 m/s. The Fitbit Ultra may be a low-cost alternative to measure the stepping activity in level, predictable environments of people with stroke and TBI who can walk at speeds ≥0.58 m/s.

Purification and Kinetics of Higher Plant NADH:Nitrate Reductase.

PubMed

Campbell, W H; Smarrelli, J

1978-04-01

Squash cotyledon (Cucurbita pepo L.) NADH:nitrate reductase (NR) was purified 150-fold with 50% recovery by a single step procedure based on the affinity of the NR for blue-Sepharose. Blue-Sepharose, which is prepared by direct coupling of Cibacron blue to Sepharose, appears to bind squash NR at the NADH site. The NR can be purified in 2 to 3 hours to a specific activity of 2 mumol of NADH oxidized/minute * milligram of protein. Corn (Zea mays L.) leaf NR was also purified to a specific activity of 6.9 mumol of NADH oxidized/minute * milligram of protein using a blue-Sepharose affinity step. The blue-Sepharose method offers the advantages of a rapid purification of plant NR to a high specific activity with reasonable recovery of total activity.The kinetic mechanism of higher plant NR was investigated using these highly purified squash and corn NR preparations. Based on initial velocity and product inhibition studies utilizing both enzymes, a two-site ping-pong mechanism is proposed for NR. This kinetic mechanism incorporates the concept of the reduced NR transferring electrons from the NADH site to a physically separated nitrate site.

Signal-activated phospholipase regulation of leukocyte chemotaxis.

PubMed

Cathcart, Martha K

2009-04-01

Signal-activated phospholipases are a recent focus of the rapidly growing field of lipid signaling. The extent of their impact on the pathways regulating diverse cell functions is beginning to be appreciated. A critical step in inflammation is the attraction of leukocytes to injured or diseased tissue. Chemotaxis of leukocytes, a requisite process for monocyte and neutrophil extravasation from the blood into tissues, is a critical step for initiating and maintaining inflammation in both acute and chronic settings. Recent studies have identified new important and required roles for two signal-activated phospholipases A2 (PLA2) in regulating chemotaxis. The two intracellular phospholipases, cPLA2alpha (Group IVA) and iPLA2beta (Group VIA), act in parallel to provide distinct lipid mediators at different intracellular sites that are both required for leukocytes to migrate toward the chemokine monocyte chemoattractant protein-1. This review will summarize the separate roles of these phospholipases as well as what is currently known about the influence of two other classes of intracellular signal-activated phospholipases, phospholipase C and phospholipase D, in regulating chemotaxis in eukaryotic cells, but particularly in human monocytes. The contributions of these phospholipases to chemotaxis both in vitro and in vivo will be highlighted.

Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains.

PubMed

Wiltshire, T; Ervin, R B; Duan, H; Bogue, M A; Zamboni, W C; Cook, S; Chung, W; Zou, F; Tarantino, L M

2015-03-01

Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

The Baby Friendly Hospital Initiative and the ten steps for successful breastfeeding. a critical review of the literature.

PubMed

Gomez-Pomar, Enrique; Blubaugh, Robert

2018-02-07

There is no doubt regarding the multiple benefits of breastfeeding for infants and society in general. Therefore, the World Health Organization (WHO) in a conjoint effort with United Nations International Children's Emergency Fund (UNICEF) developed the "Ten Steps to Successful Breastfeeding" in 1992, which became the backbone of the Baby Friendly Hospital Initiative (BFHI). Following this development, many hospitals and countries intensified their position towards creating a "breastfeeding oriented" practice. Over the past two decades, the interest increased in the BFHI and the Ten Steps. However, alongside the implementation of the initiative, extensive research continues to evaluate the benefits and dangers of the suggested practices. Hence, it is our intention to make a critical evaluation of the current BFHI and the Ten Steps recommendations in consideration of the importance of providing an evidence-based breastfeeding supported environment for our mothers and infants.

The Svalbard Integrated Arctic Earth Observing System (SIOS) ESFRI Initiative - A possible future cornerstone of European Arctic research

NASA Astrophysics Data System (ADS)

Hansen, Georg H.; Refsnes, Karin

2010-05-01

The Norwegian initiative "Svalbard Integrated Arctic Earth Observing System (SIOS) was included in the Revised Roadmap of the European Strategy Forum on Research Infrastructures (ESFRI) in 2009; an application to perform a preparatory phase project is currently under evaluation. The main aim of the SIOS initiative is to establish an Earth System observation platform in the European Arctic that is capable to match the whole scope of Earth System Models (ESM) on the observational side, ranging from solar/space-terrestrial interaction via atmosphere-ocean land-cryosphere coupling at the ground to geosphere-biosphere coupling. To this end, it is planned to integrate and upgrade all Arctic research stations on- and offshore in the Svalbard region which are currently operated by 15 nations, both European and worldwide. The initiative will also include the comprehensive marine and airborne monitoring and research activities and utilize the easy access to remote sensing data emerging from the satellite receiving activities at Longyearbyen. The already very comprehensive activity - though with limited international coordination - on Svalbard preconditions, as a first step, a thorough gap analysis of existing infrastructure in light of the needs of the modeling community and a careful design of the future overarching infrastructure. The interdisciplinary scientific character of SIOS makes the initiative well-suited to serve as a catalyser and integrator of the environmental ESFRI initiatives in the Arctic, while the truly global composition of the consortium may serve as a model for the envisaged pan-Arctic observing system SAON.

Look into my eyes: Investigating joint attention using interactive eye-tracking and fMRI in a developmental sample.

PubMed

Oberwelland, E; Schilbach, L; Barisic, I; Krall, S C; Vogeley, K; Fink, G R; Herpertz-Dahlmann, B; Konrad, K; Schulte-Rüther, M

2016-04-15

Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of "social brain" areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self-initiated JA specifically activated areas related to social cognition, decision-making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self-initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and usability of a computer-tailored pedometer-based physical activity advice for breast cancer survivors.

PubMed

De Cocker, K; Charlier, C; Van Hoof, E; Pauwels, E; Lechner, L; Bourgois, J; Spittaels, H; Vandelanotte, C; De Bourdeaudhuij, I

2015-09-01

This observational study aimed to adapt a computer-tailored step advice for the general population into a feasible advice for breast cancer survivors and to test its usability. First, several adaptations were made to the original design (adding cancer-related physical activity (PA) barriers and beliefs, and self-management strategies to improve survivors' personal control). Second, the adapted advice was evaluated in two phases: (1) a usability testing in healthy women (n = 3) and survivors (n = 6); and (2) a process evaluation during 3 weeks in breast cancer survivors (n = 8). Preliminary usability testing revealed no problems during logging-in; however, three survivors misinterpreted some questions. After refining the questionnaire and advice, survivors evaluated the advice as interesting, attractive to read, comprehensible and credible. Inactive survivors found the advice novel, but too long. The process evaluation indicated that the majority of the women (n = 5/8) reported increased steps. Monitoring step counts by using a pedometer was perceived as an important motivator to be more active. To conclude, this study provides initial support for the usability and acceptability of a computer-tailored pedometer-based PA advice for breast cancer survivors. After testing efficacy and effectiveness of this intervention, this tool can broaden the reach of PA promotion in breast cancer survivors. © 2014 John Wiley & Sons Ltd.

Lateral step initiation behavior in older adults.

PubMed

Sparto, Patrick J; Jennings, J Richard; Furman, Joseph M; Redfern, Mark S

2014-02-01

Older adults have varied postural responses during induced and voluntary lateral stepping. The purpose of the research was to quantify the occurrence of different stepping strategies during lateral step initiation in older adults and to relate the stepping responses to retrospective history of falls. Seventy community-ambulating older adults (mean age 76 y, range 70-94 y) performed voluntary lateral steps as quickly as possible to the right or left in response to a visual cue, in a blocked design. Vertical ground reaction forces were measured using a forceplate, and the number and latency of postural adjustments were quantified. Subjects were assigned to groups based on their stepping strategy. The frequency of trials with one or two postural adjustments was compared with data from 20 younger adults (mean age 38 y, range 21-58 y). Logistic regression was used to relate presence of a fall in the previous year with the number and latency of postural adjustments. In comparison with younger adults, who almost always demonstrated one postural adjustment when stepping laterally, older adults constituted a continuous distribution in the percentage of step trials made with one postural adjustment (from 0% to 100% of trials). Latencies of the initial postural adjustment and foot liftoff varied depending on the number of postural adjustments made. A history of falls was associated a larger percentage of two postural adjustments, and a longer latency of foot liftoff. In conclusion, the number and latency of postural adjustments made during voluntary lateral stepping provides additional evidence that lateral control of posture may be a critical indicator of aging. Copyright © 2013 Elsevier B.V. All rights reserved.

Lateral step initiation behavior in older adults

PubMed Central

Sparto, Patrick J; Jennings, J Richard; Furman, Joseph M; Redfern, Mark S

2013-01-01

Older adults have varied postural responses during induced and voluntary lateral stepping. The purpose of the research was to quantify the occurrence of different stepping strategies during lateral step initiation in older adults and to relate the stepping responses to retrospective history of falls. Seventy community-ambulating older adults (mean age 76 y, range 70–94 y) performed voluntary lateral steps as quickly as possible to the right or left in response to a visual cue, in a blocked design. Vertical ground reaction forces were measured using a forceplate, and the number and latency of postural adjustments were quantified. Subjects were assigned to groups based on their stepping strategy. The frequency of trials with one or two postural adjustments was compared with data from 20 younger adults (mean age 38 y, range 21–58 y). Logistic regression was used to relate presence of a fall in the previous year with the number and latency of postural adjustments. In comparison with younger adults, who almost always demonstrated one postural adjustment when stepping laterally, older adults constituted a continuous distribution in the percentage of step trials made with one postural adjustment (from 0% to 100% of trials). Latencies of the initial postural adjustment and foot liftoff varied depending on the number of postural adjustments made. A history of falls was associated a larger percentage of two postural adjustments, and a longer latency of foot liftoff. In conclusion, the number and latency of postural adjustments made during voluntary lateral stepping provides additional evidence that lateral control of posture may be a critical indicator of aging. PMID:24295896

Teaching advanced science concepts through Freshman Research Immersion

NASA Astrophysics Data System (ADS)

Wahila, M. J.; Amey-Proper, J.; Jones, W. E.; Stamp, N.; Piper, L. F. J.

2017-03-01

We have developed a new introductory physics/chemistry programme that teaches advanced science topics and practical laboratory skills to freshmen undergraduate students through the use of student-led, bona fide research activities. While many recent attempts to improve college-level physics education have focused on integrating interactive demonstrations and activities into traditional passive lectures, we have taken the idea of active-learning several steps further. Working in conjunction with several research faculty at Binghamton University, we have created a programme that puts undergraduate students on an accelerated path towards working in real research laboratories performing publishable research. Herein, we describe in detail the programme goals, structure, and educational content, and report on our promising initial student outcomes.

KSC-2014-2742

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Workers take an early morning walk along the Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

BitPredator: A Discovery Algorithm for BitTorrent Initial Seeders and Peers

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

Borges, Raymond; Patton, Robert M; Kettani, Houssain

2011-01-01

There is a large amount of illegal content being replicated through peer-to-peer (P2P) networks where BitTorrent is dominant; therefore, a framework to profile and police it is needed. The goal of this work is to explore the behavior of initial seeds and highly active peers to develop techniques to correctly identify them. We intend to establish a new methodology and software framework for profiling BitTorrent peers. This involves three steps: crawling torrent indexers for keywords in recently added torrents using Really Simple Syndication protocol (RSS), querying torrent trackers for peer list data and verifying Internet Protocol (IP) addresses from peermore » lists. We verify IPs using active monitoring methods. Peer behavior is evaluated and modeled using bitfield message responses. We also design a tool to profile worldwide file distribution by mapping IP-to-geolocation and linking to WHOIS server information in Google Earth.« less

A review for identification of initiating events in event tree development process on nuclear power plants

NASA Astrophysics Data System (ADS)

Riyadi, Eko H.

2014-09-01

Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logic model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events.

HIV Tat/P-TEFb Interaction: A Potential Target for Novel Anti-HIV Therapies.

PubMed

Asamitsu, Kaori; Fujinaga, Koh; Okamoto, Takashi

2018-04-17

Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are involved in HIV transcription from the proviral DNA integrated within the host cell genome. Among them, the virus-encoded transcriptional activator Tat is the master regulator of HIV transcription. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation and initiation by interacting with the cellular positive transcriptional elongation factor b (P-TEFb). In this review, we describe the molecular mechanism underlying how Tat activates viral transcription through interaction with P-TEFb. We propose a novel therapeutic strategy against HIV replication through blocking Tat action.

A facile one-step approach for the fabrication of polypyrrole nanowire/carbon fiber hybrid electrodes for flexible high performance solid-state supercapacitors

NASA Astrophysics Data System (ADS)

Huang, Sanqing; Han, Yichuan; Lyu, Siwei; Lin, Wenzhen; Chen, Peishan; Fang, Shaoli

2017-10-01

Wearable electronics are in high demand, requiring that all the components are flexible. Here we report a facile approach for the fabrication of flexible polypyrrole nanowire (NPPy)/carbon fiber (CF) hybrid electrodes with high electrochemical activity using a low-cost, one-step electrodeposition method. The structure of the NPPy/CF electrodes can be easily controlled by the applied electrical potential and electrodeposition time. Our NPPy/CF-based electrodes showed high flexibility, conductivity, and stability, making them ideal for flexible all-solid-state fiber supercapacitors. The resulting NPPy/CF-based supercapacitors provided a high specific capacitance of 148.4 F g-1 at 0.128 A g-1, which is much higher than for supercapacitors based on polypyrrole film/CF (38.3 F g-1) and pure CF (0.6 F g-1) under the same conditions. The NPPy/CF-based supercapacitors also showed high bending and cycling stability, retaining 84% of the initial capacitance after 500 bending cycles, and 91% of the initial capacitance after 5000 charge/discharge cycles.

Effects of prior aversive experience upon retrograde amnesia induced by hypothermia.

PubMed

Jensen, R A; Riccio, D C; Gehres, L

1975-08-01

Two experiments examined the extent to which retrograde amnesia (RA) is attenuated by prior learning experiences. In Experiment 1, rats initially received either passive avoidance training in a step-through apparatus, exposure to the apparatus, or noncontingent footshock. When training on a second but different passive avoidance task was followed by hypothermia treatment, RA was obtained only in the latter two groups. In Experiment 2, one-way active avoidance training, yoked noncontingent shocks, or apparatus exposure constituted the initial experience. Subsequent step-down passive avoidance training and amnestic treatment resulted in memory loss for the prior apparatus exposure group, but not for either of the preshocked conditions. These experiments demonstrate that certain types of prior aversive experience can substantially modify the magnitude of RA, and, in conjunction with other familiarization studies, emphasize a paradox for interpretations of RA based solely upon CNS disruption. The possibility that hypothermia treatment serves as an important contextual or encoding cue necessary for memory retrieval was considered. It was suggested that prior experience may block RA by enabling rats to differentiate training and treatment conditions.

Ergonomic analyses within the French transport and logistics sector: first steps towards a new "act elsewhere" prevention approach.

PubMed

Wioland, Liên

2013-10-01

Statistics from the French Employee National Health Insurance Fund indicate high accident levels in the transport sector. This study represents initial thinking on a new approach to transport sector prevention based on the assumption that a work situation could be improved by acting on another interconnected work situation. Ergonomic analysis of two connected work situations, involving the road haulage drivers and cross-docking platform employees, was performed to test this assumption. Our results show that drivers are exposed to a number of identified risks, but their multiple tasks raise the question of activity intensification. The conditions, under which the drivers will perform their work and take to the road, are partly determined by the quality and organisation of the platform with which they interact. We make a number of recommendations (e.g. changing handling equipment, re-appraising certain jobs) to improve platform organisation and employee working conditions with the aim of also improving driver conditions. These initial steps in this prevention approach appear promising, but more detailed investigation is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Initial and long-term bond strengths of one-step self-etch adhesives with silane coupling agent to enamel-dentin-composite in combined situation.

PubMed

Mamanee, Teerapong; Takahashi, Masahiro; Nakajima, Masatoshi; Foxton, Richard M; Tagami, Junji

2015-01-01

This study evaluated the effect of adding silane coupling agent on initial and long-term bond strengths of one-step self-etch adhesives to enamel-dentin-composite in combined situation. Cervical cavities were prepared on extracted molars and filled with Clearfil AP-X. After water-storage for one-week, the filled teeth were sectioned in halves to expose enamel, dentin and composite surfaces and then enamel-dentin-composite surface was totally applied with one of adhesive treatments (Clearfil SE One, Clearfil SE One with Clearfil Porcelain Bond Activator, Beautibond Multi, Beautibond Multi with Beautibond Multi PR Plus and Scotchbond Universal). After designed period, micro-shear bond strengths (µSBSs) to each substrate were determined. For each period of water-storage, additive silane treatments significantly increased µSBS to composite (p<0.001). On the other hand, they significantly decreased µSBS to dentin (p<0.001), although did not have adverse effect on µSBS to enamel (p>0.05). Moreover, the stability of µSBS was depended on materials and substrates used.

A facile one-step approach for the fabrication of polypyrrole nanowire/carbon fiber hybrid electrodes for flexible high performance solid-state supercapacitors.

PubMed

Huang, Sanqing; Han, Yichuan; Lyu, Siwei; Lin, Wenzhen; Chen, Peishan; Fang, Shaoli

2017-10-27

Wearable electronics are in high demand, requiring that all the components are flexible. Here we report a facile approach for the fabrication of flexible polypyrrole nanowire (NPPy)/carbon fiber (CF) hybrid electrodes with high electrochemical activity using a low-cost, one-step electrodeposition method. The structure of the NPPy/CF electrodes can be easily controlled by the applied electrical potential and electrodeposition time. Our NPPy/CF-based electrodes showed high flexibility, conductivity, and stability, making them ideal for flexible all-solid-state fiber supercapacitors. The resulting NPPy/CF-based supercapacitors provided a high specific capacitance of 148.4 F g -1 at 0.128 A g -1 , which is much higher than for supercapacitors based on polypyrrole film/CF (38.3 F g -1 ) and pure CF (0.6 F g -1 ) under the same conditions. The NPPy/CF-based supercapacitors also showed high bending and cycling stability, retaining 84% of the initial capacitance after 500 bending cycles, and 91% of the initial capacitance after 5000 charge/discharge cycles.

A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

PubMed

Velasco, Silvia; Ibrahim, Mahmoud M; Kakumanu, Akshay; Garipler, Görkem; Aydin, Begüm; Al-Sayegh, Mohamed Ahmed; Hirsekorn, Antje; Abdul-Rahman, Farah; Satija, Rahul; Ohler, Uwe; Mahony, Shaun; Mazzoni, Esteban O

2017-02-02

Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions. Subsequently, Isl1/Lhx3 binding shifts from one set of targets to another, controlling regulatory region activity and gene expression as cell differentiation progresses. Binding of Isl1/Lhx3 to later motor neuron enhancers depends on the Ebf and Onecut TFs, which are induced by Ngn2 during the programming process. Thus, motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic. Copyright © 2017 Elsevier Inc. All rights reserved.

Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.

PubMed

Van Calster, B; Bobdiwala, S; Guha, S; Van Hoorde, K; Al-Memar, M; Harvey, R; Farren, J; Kirk, E; Condous, G; Sur, S; Stalder, C; Timmerman, D; Bourne, T

2016-11-01

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2). This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of < 5%. On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity. PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Self-triggered assistive stimulus training improves step initiation in persons with Parkinson’s disease

PubMed Central

2013-01-01

Background Prior studies demonstrated that hesitation-prone persons with Parkinson’s disease (PDs) acutely improve step initiation using a novel self-triggered stimulus that enhances lateral weight shift prior to step onset. PDs showed reduced anticipatory postural adjustment (APA) durations, earlier step onsets, and faster 1st step speed immediately following stimulus exposure. Objective This study investigated the effects of long-term stimulus exposure. Methods Two groups of hesitation-prone subjects with Parkinson’s disease (PD) participated in a 6-week step-initiation training program involving one of two stimulus conditions: 1) Drop. The stance-side support surface was lowered quickly (1.5 cm); 2) Vibration. A short vibration (100 ms) was applied beneath the stance-side support surface. Stimuli were self-triggered by a 5% reduction in vertical force under the stance foot during the APA. Testing was at baseline, immediately post-training, and 6 weeks post-training. Measurements included timing and magnitude of ground reaction forces, and step speed and length. Results Both groups improved their APA force modulation after training. Contrary to previous results, neither group showed reduced APA durations or earlier step onset times. The vibration group showed 55% increase in step speed and a 39% increase in step length which were retained 6 weeks post-training. The drop group showed no stepping-performance improvements. Conclusions The acute sensitivity to the quickness-enhancing effects of stimulus exposure demonstrated in previous studies was supplanted by improved force modulation following prolonged stimulus exposure. The results suggest a potential approach to reduce the severity of start hesitation in PDs, but further study is needed to understand the relationship between short- and long-term effects of stimulus exposure. PMID:23363975

Biomechanics of Step Initiation After Balance Recovery With Implications for Humanoid Robot Locomotion.

PubMed

Miller Buffinton, Christine; Buffinton, Elise M; Bieryla, Kathleen A; Pratt, Jerry E

2016-03-01

Balance-recovery stepping is often necessary for both a human and humanoid robot to avoid a fall by taking a single step or multiple steps after an external perturbation. The determination of where to step to come to a complete stop has been studied, but little is known about the strategy for initiation of forward motion from the static position following such a step. The goal of this study was to examine the human strategy for stepping by moving the back foot forward from a static, double-support position, comparing parameters from normal step length (SL) to those from increasing SLs to the point of step failure, to provide inspiration for a humanoid control strategy. Healthy young adults instrumented with joint reflective markers executed a prescribed-length step from rest while marker positions and ground reaction forces (GRFs) were measured. The participants were scaled to the Gait2354 model in opensim software to calculate body kinematic and joint kinetic parameters, with further post-processing in matlab. With increasing SL, participants reduced both static and push-off back-foot GRF. Body center of mass (CoM) lowered and moved forward, with additional lowering at the longer steps, and followed a path centered within the initial base of support (BoS). Step execution was successful if participants gained enough forward momentum at toe-off to move the instantaneous capture point (ICP) to within the BoS defined by the final position of both feet on the front force plate. All lower extremity joint torques increased with SL except ankle joint. Front knee work increased dramatically with SL, accompanied by decrease in back-ankle work. As SL increased, the human strategy changed, with participants shifting their CoM forward and downward before toe-off, thus gaining forward momentum, while using less propulsive work from the back ankle and engaging the front knee to straighten the body. The results have significance for human motion, suggesting the upper limit of the SL that can be completed with back-ankle push-off before additional knee flexion and torque is needed. For biped control, the results support stability based on capture-point dynamics and suggest strategy for center-of-mass trajectory and distribution of ground force reactions that can be compared with robot controllers for initiation of gait after recovery steps.

Inverting the planning gradient: adjustment of grasps to late segments of multi-step object manipulations.

PubMed

Mathew, Hanna; Kunde, Wilfried; Herbort, Oliver

2017-05-01

When someone grasps an object, the grasp depends on the intended object manipulation and usually facilitates it. If several object manipulation steps are planned, the first step has been reported to primarily determine the grasp selection. We address whether the grasp can be aligned to the second step, if the second step's requirements exceed those of the first step. Participants grasped and rotated a dial first by a small extent and then by various extents in the opposite direction, without releasing the dial. On average, when the requirements of the first and the second step were similar, participants mostly aligned the grasp to the first step. When the requirements of the second step were considerably higher, participants aligned the grasp to the second step, even though the first step still had a considerable impact. Participants employed two different strategies. One subgroup initially aligned the grasp to the first step and then ceased adjusting the grasp to either step. Another group also initially aligned the grasp to the first step and then switched to aligning it primarily to the second step. The data suggest that participants are more likely to switch to the latter strategy when they experienced more awkward arm postures. In summary, grasp selections for multi-step object manipulations can be aligned to the second object manipulation step, if the requirements of this step clearly exceed those of the first step and if participants have some experience with the task.

Ada protein-RNA polymerase sigma subunit interaction and alpha subunit-promoter DNA interaction are necessary at different steps in transcription initiation at the Escherichia coli Ada and aidB promoters.

PubMed

Landini, P; Bown, J A; Volkert, M R; Busby, S J

1998-05-22

The methylated form of the Ada protein (meAda) binds the ada and aidB promoters between 60 and 40 base pairs upstream from the transcription start and activates transcription of the Escherichia coli ada and aidB genes. This region is also a binding site for the alpha subunit of RNA polymerase and resembles the rrnB P1 UP element in A/T content and location relative to the core promoter. In this report, we show that deletion of the C-terminal domain of the alpha subunit severely decreases meAda-independent binding of RNA polymerase to ada and aidB, affecting transcription initiation at these promoters. We provide evidence that meAda activates transcription by direct interaction with the C-terminal domain of RNA polymerase sigma70 subunit (amino acids 574-613). Several negatively charged residues in the sigma70 C-terminal domain are important for transcription activation by meAda; in particular, a glutamic acid to valine substitution at position 575 has a dramatic effect on meAda-dependent transcription. Based on these observations, we propose that the role of the alpha subunit at ada and aidB is to allow initial binding of RNA polymerase to the promoters. However, transcription initiation is dependent on meAda-sigma70 interaction.

Optimization of pyrochlore catalysts for the dry reforming of methane

NASA Astrophysics Data System (ADS)

Polo Garzon, Felipe

The conversion of methane into syngas (a mixture of CO and H2), which can be further converted into a variety of chemicals and particularly liquid fuels, is of growing importance given recent increases in methane production world-wide. Furthermore, since using CO2 as the co-feed offers many environmental advantages, dry reforming of methane (DRM, CH4 + CO2 [special character omitted] 2CO + 2H 2) has received renewed attention. In recent years, experimentalists have shown that the Rh-substituted lanthanum zirconate pyrochlore (LRhZ) material is catalytically active for DRM, exhibits long-term thermal stability and resists deactivation; however, previous to this doctoral work, a detailed understanding of the reaction mechanism on pyrochlore catalyst surfaces was still scarce, making it difficult to optimize this material. In this work, initial computational efforts employing density functional theory (DFT) showed the plane (111) of the LRhZ crystal structure as the one catalytically active for DRM. In addition, the primary reaction pathway was identified, along with two rate determining steps (RDSs), the CH2 oxygenation step and the CHO dehydrogenation step, which lie on the CH 4 dehydrogenation/oxygenation path. The mechanistic understanding of DRM over LRhZ was further developed using steady-state isotopic transient kinetic analysis (SSITKA). Reversible adsorption of CO2 on the surface was observed, along with short surface residence times (< 0.6 s) at 650 and 800 °C, and increasing turnover frequencies with temperature. Comparisons between isotopic responses supported the DFT-derived reaction mechanism. Furthermore, isotopic transient kinetics confirmed that all metal atoms (Rh, Zr and La) on the surface are involved in the reaction mechanism, as previously pointed by DFT calculations. A DFT-based microkinetic model that predicts the reaction performance at different conditions was built. The model was validated against experimental data, showing remarkable agreement, which further confirmed the reliability of the DFT data. Computational analysis of one of the RDSs (the CHO dehydrogenation step) suggested Pd as an effective co-dopant to reduce the activation barrier of this step. This bimetallic Rh-Pd-substituted lanthanum zirconate pyrochlore (Rh-Pd-LZ) was synthesized, characterized and tested. The Rh-Pd-LZ catalyst successfully increased conversions at high temperatures while providing H 2 to CO ratios close to unity; thus fostering DRM and inhibiting the competing reaction, the reverse water gas shift reaction (RWGS, CO2 + H2 [special character omitted] CO + H2O). The Rh-Pd-LZ catalyst outperformed the initial catalyst, the LRhZ, at high temperatures.

Intracellular Trafficking and Persistence of Acinetobacter baumannii Requires Transcription Factor EB

PubMed Central

Parra-Millán, Raquel; Guerrero-Gómez, David; Ayerbe-Algaba, Rafael; Pachón-Ibáñez, Maria Eugenia; Miranda-Vizuete, Antonio

2018-01-01

ABSTRACT Acinetobacter baumannii is a significant human pathogen associated with hospital-acquired infections. While adhesion, an initial and important step in A. baumannii infection, is well characterized, the intracellular trafficking of this pathogen inside host cells remains poorly studied. Here, we demonstrate that transcription factor EB (TFEB) is activated after A. baumannii infection of human lung epithelial cells (A549). We also show that TFEB is required for the invasion and persistence inside A549 cells. Consequently, lysosomal biogenesis and autophagy activation were observed after TFEB activation which could increase the death of A549 cells. In addition, using the Caenorhabditis elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. These results identify TFEB as a conserved key factor in the pathogenesis of A. baumannii. IMPORTANCE Adhesion is an initial and important step in Acinetobacter baumannii infections. However, the mechanism of entrance and persistence inside host cells is unclear and remains to be understood. In this study, we report that, in addition to its known role in host defense against Gram-positive bacterial infection, TFEB also plays an important role in the intracellular trafficking of A. baumannii in host cells. TFEB was activated shortly after A. baumannii infection and is required for its persistence within host cells. Additionally, using the C. elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. PMID:29600279

Assimilation of the ESA CCI Soil Moisture ACTIVE and PASSIVE Product into the SURFEX Land Surface Model using the Ensemble Transform Kalman Filter

NASA Astrophysics Data System (ADS)

Blyverket, J.; Hamer, P.; Bertino, L.; Lahoz, W. A.

2017-12-01

The European Space Agency Climate Change Initiative for soil moisture (ESA CCI SM) was initiated in 2012 for a period of six years, the objective for this period was to produce the most complete and consistent global soil moisture data record based on both active and passive sensors. The ESA CCI SM products consist of three surface soil moisture datasets: The ACTIVE product and the PASSIVE product were created by fusing scatterometer and radiometer soil moisture data, respectively. The COMBINED product is a blended product based on the former two datasets. In this study we assimilate globally both the ACTIVE and PASSIVE product at a 25 km spatial resolution. The different satellite platforms have different overpass times, an observation is mapped to the hours 00.00, 06.00, 12.00 or 18.00 if it falls within a 3 hour window centred at these times. We use the SURFEX land surface model with the ISBA diffusion scheme for the soil hydrology. For the assimilation routine we apply the Ensemble Transform Kalman Filter (ETKF). The land surface model is driven by perturbed MERRA-2 atmospheric forcing data, which has a temporal resolution of one hour and is mapped to the SURFEX model grid. Bias between the land surface model and the ESA CCI product is removed by cumulative distribution function (CDF) matching. This work is a step towards creating a global root zone soil moisture product from the most comprehensive satellite surface soil moisture product available. As a first step we consider the period from 2010 - 2016. This allows for comparison against other global root zone soil moisture products (SMAP Level 4, which is independent of the ESA CCI SM product).

The Kinetics of Myosin Light Chain Kinase Activation of Smooth Muscle Myosin in an In Vitro Model System

PubMed Central

Hong, Feng; Facemyer, Kevin C.; Carter, Michael S.; Jackson, Del R.; Haldeman, Brian D.; Ruana, Nick; Sutherland, Cindy; Walsh, Michael P.; Cremo, Christine R.; Baker, Josh E.

2013-01-01

During activation of smooth muscle contraction, one myosin light chain kinase (MLCK) molecule rapidly phosphorylates many smooth muscle myosin (SMM) molecules, suggesting that muscle activation rates are influenced by the kinetics of MLCK-SMM interactions. To determine the rate-limiting step underlying activation of SMM by MLCK, we measured the kinetics of calcium-calmodulin (Ca2+-CaM)-MLCK-mediated SMM phosphorylation and the corresponding initiation of SMM-based F-actin motility in an in vitro system with SMM attached to a coverslip surface. Fitting the time course of SMM phosphorylation to a kinetic model gave an initial phosphorylation rate, kpo, of ~1.17 heads s−1·MLCK−1. Also we measured the dwell time of single QD-labeled MLCK molecules interacting with surface-attached SMM and phosphorylated SMM using total internal reflection fluorescence microscopy. From these data, the dissociation rate constant from phosphorylated SMM was 0.80 s−1, which was similar to kpo mentioned above and with rates measured in solution. This dissociation rate was essentially independent of the phosphorylation state of SMM. From calculations using our measured dissociation rates and Kds, and estimates of [SMM] and [MLCK] in muscle, we predict that the dissociation of MLCK from phosphorylated SMM is rate-limiting and that the rate of the phosphorylation step is faster than this dissociation rate. Also, association to SMM (11-46 s−1) would be much faster than to pSMM (<0.1-0.2 s−1). This suggests that the probability of MLCK interacting with unphosphorylated versus pSMM is 55-460 times greater. This would avoid sequestering MLCK to unproductive interactions with previously phosphorylated SMM, potentially leading to faster rates of phosphorylation in muscle. PMID:24144337

29 CFR 1956.52 - Completed developmental steps and certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Completed developmental steps and certification. 1956.52... PLANS New York § 1956.52 Completed developmental steps and certification. (a) In accordance with 29 CFR..., 2006 as having successfully completed all developmental steps specified in the plan as initially...

40 CFR 35.2203 - Step 7 projects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Step 7 projects. 35.2203 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2203 Step 7 projects. (a) Prior to initiating action to acquire real property, a Step 7 grantee shall submit for Regional...

Soviet Foreign Policy in the Middle East: Internal and External Determinants.

DTIC Science & Technology

1987-06-01

Soviet-Egyptian relations and four involving Soviet-Syrian relations. Each event signifies a juncture at which Soviet policymakers had to make fundmental ...actor on the international scene. In order to promote a more active global strategy many of the more rigid doctrinal principles of the Stalin era were...establishment of a national-democratic state could be viewed as a positive first step towards socialism, even if it was initially based on capitalist principles

Application of a mixed culture of adapted acidophilic bacteria in two-step bioleaching of spent lithium-ion laptop batteries

NASA Astrophysics Data System (ADS)

Heydarian, Ahmad; Mousavi, Seyyed Mohammad; Vakilchap, Farzane; Baniasadi, Mahsa

2018-02-01

The rapid increase in the production of electrical and electronic equipment, along with higher consumption of these products, has caused defective and obsolete equipment to accumulate in the environment. In this research, bioleaching of spent lithium-ion batteries (LIBs) used in laptops is carried out under two-step condition based on the bacterial activities of a mixture of Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans. First, the best inoculum ratio of two acidophilic bacteria for the mixed culture is obtained. Next, adaptation is carried out successfully and the solid-to-liquid ratio reaches 40 g L-1. Response surface methodology is utilized to optimize the effective variables of initial pH, iron sulfate and sulfur concentrations. The maximum recovery of metal is about 99.2% for Li, 50.4% for Co and 89.4% for Ni under optimum conditions of 36.7 g L-1 iron sulfate concentration, 5.0 g L-1 sulfur concentration and initial pH of 1.5 for the best inoculum ratio of 3/2. Results of FE-SEM, XRD and FTIR analysis before and after bioleaching confirm that bacterial activity is a promising and effective route for metal recovery from spent LIBs. Toxicity assessment tests demonstrate the suitability of the bioleached residual as a nonhazardous material that meets environmental limitations for safe disposal.

Energy landscape-driven non-equilibrium evolution of inherent structure in disordered material

DOE PAGES

Fan, Yue; Iwashita, Takuya; Egami, Takeshi

2017-05-19

Complex states in glasses can be neatly expressed by the potential energy landscape (PEL). But, because PEL is highly multi-dimensional it is difficult to describe how the system moves around in PEL. We demonstrate that it is possible to predict the evolution of macroscopic state in a metallic glass, such as ageing and rejuvenation, through a set of simple equations describing excitations in the PEL. The key to this simplification is the realization that the step of activation from the initial state to the saddle point in PEL and the following step of relaxation to the final state are essentiallymore » decoupled. Furthermore, the model shows that the interplay between activation and relaxation in PEL is the key driving force that simultaneously explains both the equilibrium of supercooled liquid and the thermal hysteresis observed in experiments. It further predicts anomalous peaks in truncated thermal scanning, validated by independent molecular dynamics simulation.« less

Function-oriented synthesis: biological evaluation of laulimalide analogues derived from a last step cross metathesis diversification strategy.

PubMed

Mooberry, Susan L; Hilinski, Michael K; Clark, Erin A; Wender, Paul A

2008-01-01

Laulimalide is a potent microtubule stabilizing agent and a promising anticancer therapeutic lead. The identification of stable, efficacious and accessible analogues is critical to clinically exploiting this novel lead. To determine which structural features of laulimalide are required for beneficial function and thus for accessing superior clinical candidates, a series of side chain analogues were prepared through a last step cross metathesis diversification strategy and their biological activities were evaluated. Five analogues, differing in potency from 233 nM to 7.9 muM, effectively inhibit cancer cell proliferation. Like laulimalide, they retain activity against multidrug resistant cells, stabilize microtubules and cause the formation of aberrant mitotic spindles, mitotic accumulation, Bcl-2 phosphorylation and initiation of apoptosis. Structural modifications in the C 23-C 27 dihydropyran side chain can be made without changing the overall mechanism of action, but it is clear that this subunit has more than a bystander role.

Successive membrane separation processes simplify concentration of lipases produced by Aspergillus niger by solid-state fermentation.

PubMed

Reinehr, Christian Oliveira; Treichel, Helen; Tres, Marcus Vinicius; Steffens, Juliana; Brião, Vandré Barbosa; Colla, Luciane Maria

2017-06-01

In this study, we developed a simplified method for producing, separating, and concentrating lipases derived from solid-state fermentation of agro-industrial residues by filamentous fungi. First, we used Aspergillus niger to produce lipases with hydrolytic activity. We analyzed the separation and concentration of enzymes using membrane separation processes. The sequential use of microfiltration and ultrafiltration processes made it possible to obtain concentrates with enzymatic activities much higher than those in the initial extract. The permeate flux was higher than 60 L/m 2 h during microfiltration using 20- and 0.45-µm membranes and during ultrafiltration using 100- and 50-kDa membranes, where fouling was reversible during the filtration steps, thereby indicating that the fouling may be removed by cleaning processes. These results demonstrate the feasibility of lipase production using A. niger by solid-state fermentation of agro-industrial residues, followed by successive tangential filtration with membranes, which simplify the separation and concentration steps that are typically required in downstream processes.

A two step method to treat variable winds in fallout smearing codes. Master's thesis

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

Hopkins, A.T.

1982-03-01

A method was developed to treat non-constant winds in fallout smearing codes. The method consists of two steps: (1) location of the curved hotline (2) determination of the off-hotline activity. To locate the curved hotline, the method begins with an initial cloud of 20 discretely-sized pancake clouds, located at altitudes determined by weapon yield. Next, the particles are tracked through a 300 layer atmosphere, translating with different winds in each layer. The connection of the 20 particles' impact points is the fallout hotline. The hotline location was found to be independent of the assumed particle size distribution in the stabilizedmore » cloud. The off-hotline activity distribution is represented as a two-dimensional gaussian function, centered on the curved hotline. Hotline locator model results were compared to numerical calculations of hypothetical 100 kt burst and to the actual hotline produced by the Castle-Bravo 15 Mt nuclear test.« less

AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

PubMed

Mahboubi, Hicham; Koromilas, Antonis E; Stochaj, Ursula

2016-10-01

Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Simplified Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2005-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two time step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting rates of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates are used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx are obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cells

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

Nishimoto, Arata, E-mail: anishimo@yamaguchi-u.ac.jp; Kugimiya, Naruji; Hosoyama, Toru

2013-08-30

Highlights: •JAB1 interacted with unphosphorylated STAT3 in the nucleus. •JAB1 knockdown tended to increase nuclear STAT3 expression. •JAB1 knockdown significantly decreased unphosphorylated STAT3 DNA-binding activity. •JAB1 knockdown significantly decreased MDR1, NANOG, and VEGF expressions. •Nuclear JAB1, but not nuclear STAT3, correlated with STAT3 DNA-binding activity. -- Abstract: Recent studies have revealed that unphosphorylated STAT3 forms a dimer, translocates to the nucleus, binds to the STAT3 binding site, and activates the transcription of STAT3 target genes, thereby playing an important role in oncogenesis in addition to phosphorylated STAT3. Among signaling steps of unphosphorylated STAT3, nuclear translocation and target DNA-binding are themore » critical steps for its activation. Therefore, elucidating the regulatory mechanism of these signaling steps of unphosphorylated STAT3 is a potential step in the discovery of a novel cancer drug. However, the mechanism of unphosphorylated STAT3 binding to the promoter of target genes remains unclear. In this study, we focused on Jun activation domain-binding protein 1 (JAB1) as a candidate protein that regulates unphosphorylated STAT3 DNA-binding activity. Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation). On the other hand, phosphorylated STAT3 did not exist in the nucleus of COLO205 cells at the basal state. Immunoprecipitation using nuclear extract of COLO205 cells revealed that JAB1 interacted with unphosphorylated STAT3. To investigate the effect of JAB1 on unphosphorylated STAT3 activity, RNAi studies were performed. Although JAB1 knockdown tended to increase nuclear STAT3 expression, it significantly decreased unphosphorylated STAT3 DNA-binding activity. Subsequently, JAB1 knockdown significantly decreased the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target genes. Furthermore, the expression level of nuclear JAB1, but not nuclear STAT3, correlated with unphosphorylated STAT3 DNA-binding activity between COLO205 and LoVo cells. Taken together, these results suggest that nuclear JAB1 positively regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cell line COLO205.« less

Foot and Ankle Kinematics During Descent From Varying Step Heights.

PubMed

Gerstle, Emily E; O'Connor, Kristian; Keenan, Kevin G; Cobb, Stephen C

2017-12-01

In the general population, one-third of incidences during step negotiation occur during the transition to level walking. Furthermore, falls during curb negotiation are a common cause of injury in older adults. Distal foot kinematics may be an important factor in determining injury risk associated with transition step negotiation. The purpose of this study was to identify foot and ankle kinematics of uninjured individuals during descent from varying step heights. A 7-segment foot model was used to quantify kinematics as participants walked on a level walkway, stepped down a single step (heights: 5 cm, 15 cm, 25 cm), and continued walking. As step height increased, landing strategy transitioned from the rearfoot to the forefoot, and the rearfoot, lateral and medial midfoot, and medial forefoot became more plantar flexed. During weight acceptance, sagittal plane range of motion of the rearfoot, lateral midfoot, and medial and lateral forefoot increased as step height increased. The changes in landing strategy and distal foot function suggest a less stable ankle position at initial contact and increased demand on the distal foot at initial contact and through the weight acceptance phase of transition step negotiation as step height increases.

Sono-photocatalytic production of hydrogen by interface modified metal oxide insulators.

PubMed

Senevirathne, Rushdi D; Abeykoon, Lahiru K; De Silva, Nuwan L; Yan, Chang-Feng; Bandara, Jayasundera

2018-07-01

Dielectric oxide materials are well-known insulators that have many applications in catalysis as well as in device manufacturing industries. However, these dielectric materials cannot be employed directly in photochemical reactions that are initiated by the absorption of UV-Vis photons. Despite their insensitivity to solar energy, dielectric materials can be made sono-photoactive even for low energy IR photons by modifications of the interfacial properties of dielectric materials by noble metals and metal oxides. In this investigation, by way of interface modification of dielectric MgO nanoparticles by Ag metal and Ag 2 O nanoparticles, IR photon initiated sono-photocatalytic activity of MgO is reported. The observed photocatalytic activity is found to be the synergic action of both IR light and sonication effect and sonication assisted a multi-step, sub-bandgap excitation of electrons in the MgO is proposed for the observed catalytic activity of Ag/Ag 2 O coated MgO nanoparticles. Our investigation reveals that other dielectric materials such as silver coated SiO 2 and Al 2 O 3 also exhibit IR active sono-photocatalytic activity. Copyright © 2018 Elsevier B.V. All rights reserved.

A Psychometric Approach to Theory-Based Behavior Change Intervention Development: Example From the Colorado Meaning-Activity Project.

PubMed

Masters, Kevin S; Ross, Kaile M; Hooker, Stephanie A; Wooldridge, Jennalee L

2018-05-18

There has been a notable disconnect between theories of behavior change and behavior change interventions. Because few interventions are both explicitly and adequately theory-based, investigators cannot assess the impact of theory on intervention effectiveness. Theory-based interventions, designed to deliberately engage the theory's proposed mechanisms of change, are needed to adequately test theories. Thus, systematic approaches to theory-based intervention development are needed. This article will introduce and discuss the psychometric method of developing theory-based interventions. The psychometric approach to intervention development utilizes basic psychometric principles at each step of the intervention development process in order to build a theoretically driven intervention to, subsequently, be tested in process (mechanism) and outcome studies. Five stages of intervention development are presented as follows: (i) Choice of theory; (ii) Identification and characterization of key concepts and expected relations; (iii) Intervention construction; (iv) Initial testing and revision; and (v) Empirical testing of the intervention. Examples of this approach from the Colorado Meaning-Activity Project (COMAP) are presented. Based on self-determination theory integrated with meaning or purpose, and utilizing a motivational interviewing approach, the COMAP intervention is individually based with an initial interview followed by smart phone-delivered interventions for increasing daily activity. The psychometric approach to intervention development is one method to ensure careful consideration of theory in all steps of intervention development. This structured approach supports developing a research culture that endorses deliberate and systematic operationalization of theory into behavior change intervention from the outset of intervention development.

Adaptation of catch-up saccades during the initiation of smooth pursuit eye movements.

PubMed

Schütz, Alexander C; Souto, David

2011-04-01

Reduction of retinal speed and alignment of the line of sight are believed to be the respective primary functions of smooth pursuit and saccadic eye movements. As the eye muscles strength can change in the short-term, continuous adjustments of motor signals are required to achieve constant accuracy. While adaptation of saccade amplitude to systematic position errors has been extensively studied, we know less about the adaptive response to position errors during smooth pursuit initiation, when target motion has to be taken into account to program saccades, and when position errors at the saccade endpoint could also be corrected by increasing pursuit velocity. To study short-term adaptation (250 adaptation trials) of tracking eye movements, we introduced a position error during the first catch-up saccade made during the initiation of smooth pursuit-in a ramp-step-ramp paradigm. The target position was either shifted in the direction of the horizontally moving target (forward step), against it (backward step) or orthogonally to it (vertical step). Results indicate adaptation of catch-up saccade amplitude to back and forward steps. With vertical steps, saccades became oblique, by an inflexion of the early or late saccade trajectory. With a similar time course, post-saccadic pursuit velocity was increased in the step direction, adding further evidence that under some conditions pursuit and saccades can act synergistically to reduce position errors.

TAF(II)250: a transcription toolbox.

PubMed

Wassarman, D A; Sauer, F

2001-08-01

Activation of RNA-polymerase-II-dependent transcription involves conversion of signals provided by gene-specific activator proteins into the synthesis of messenger RNA. This conversion requires dynamic structural changes in chromatin and assembly of general transcription factors (GTFs) and RNA polymerase II at core promoter sequence elements surrounding the transcription start site of genes. One hallmark of transcriptional activation is the interaction of DNA-bound activators with coactivators such as the TATA-box binding protein (TBP)-associated factors (TAF(II)s) within the GTF TFIID. TAF(II)250 possesses a variety of activities that are likely to contribute to the initial steps of RNA polymerase II transcription. TAF(II)250 is a scaffold for assembly of other TAF(II)s and TBP into TFIID, TAF(II)250 binds activators to recruit TFIID to particular promoters, TAF(II)250 regulates binding of TBP to DNA, TAF(II)250 binds core promoter initiator elements, TAF(II)250 binds acetylated lysine residues in core histones, and TAF(II)250 possesses protein kinase, ubiquitin-activating/conjugating and acetylase activities that modify histones and GTFs. We speculate that these activities achieve two goals--(1) they aid in positioning and stabilizing TFIID at particular promoters, and (2) they alter chromatin structure at the promoter to allow assembly of GTFs--and we propose a model for how TAF(II)250 converts activation signals into active transcription.

Activated carbons from potato peels: The role of activation agent and carbonization temperature of biomass on their use as sorbents for bisphenol A uptake from aqueous solutions

NASA Astrophysics Data System (ADS)

Arampatzidou, An; Deliyanni, Eleni A.

2015-04-01

Activated carbons prepared from potato peels, a solid waste by product, and activated with different activating chemicals, have been studied for the adsorption of an endocrine disruptor (Bisphenol-A) from aqueous solutions. The potato peels biomass was activated with phosphoric acid, KOH and ZnCl2. The different activating chemicals were tested in order the better activation agent to be found. The carbons were carbonized by pyrolysis, in one step procedure, at three different temperatures in order the role of the temperature of carbonization to be pointed out. The porous texture and the surface chemistry of the prepared activated carbons were characterized by Nitrogen adsorption (BET), Scanning Electron Microscope (SEM), thermal analysis (DTA) and Fourier Transform Infrared Spectroscopy (FTIR). Batch experiments were performed to investigate the effect of pH, the adsorbent dose, the initial bisphenol A concentration and temperature. Equilibrium adsorption data were analyzed by Langmuir and Freundlich isotherms. The thermodynamic parameters such as the change of enthalpy (ΔH0), entropy (ΔS0) and Gibb's free energy (ΔG0) of adsorption systems were also evaluated. The adsorption capacity calculated from the Langmuir isotherm was found to be 450 mg g-1 at an initial pH 3 at 25 °C for the phosphoric acid activated carbon, that make the activated carbon a promising adsorbent material.

A Graphical User Interface for Software-assisted Tracking of Protein Concentration in Dynamic Cellular Protrusions.

PubMed

Saha, Tanumoy; Rathmann, Isabel; Galic, Milos

2017-07-11

Filopodia are dynamic, finger-like cellular protrusions associated with migration and cell-cell communication. In order to better understand the complex signaling mechanisms underlying filopodial initiation, elongation and subsequent stabilization or retraction, it is crucial to determine the spatio-temporal protein activity in these dynamic structures. To analyze protein function in filopodia, we recently developed a semi-automated tracking algorithm that adapts to filopodial shape-changes, thus allowing parallel analysis of protrusion dynamics and relative protein concentration along the whole filopodial length. Here, we present a detailed step-by-step protocol for optimized cell handling, image acquisition and software analysis. We further provide instructions for the use of optional features during image analysis and data representation, as well as troubleshooting guidelines for all critical steps along the way. Finally, we also include a comparison of the described image analysis software with other programs available for filopodia quantification. Together, the presented protocol provides a framework for accurate analysis of protein dynamics in filopodial protrusions using image analysis software.

Oxidation of F-actin controls the terminal steps of cytokinesis

PubMed Central

Frémont, Stéphane; Hammich, Hussein; Bai, Jian; Wioland, Hugo; Klinkert, Kerstin; Rocancourt, Murielle; Kikuti, Carlos; Stroebel, David; Romet-Lemonne, Guillaume; Pylypenko, Olena; Houdusse, Anne; Echard, Arnaud

2017-01-01

Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission. MICAL1 is recruited to the abscission site by the Rab35 GTPase through a direct interaction with a flat three-helix domain found in MICAL1 C terminus. Mechanistically, in vitro assays on single actin filaments demonstrate that MICAL1 is activated by Rab35. Moreover, in our experimental conditions, MICAL1 does not act as a severing enzyme, as initially thought, but instead induces F-actin depolymerization from both ends. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division. PMID:28230050

Subsurface oxide plays a critical role in CO2 activation by Cu(111) surfaces to form chemisorbed CO2, the first step in reduction of CO2.

PubMed

Favaro, Marco; Xiao, Hai; Cheng, Tao; Goddard, William A; Yano, Junko; Crumlin, Ethan J

2017-06-27

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide is essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.

Modelling reveals kinetic advantages of co-transcriptional splicing.

PubMed

Aitken, Stuart; Alexander, Ross D; Beggs, Jean D

2011-10-01

Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

Subsurface oxide plays a critical role in CO2 activation by Cu(111) surfaces to form chemisorbed CO2, the first step in reduction of CO2

PubMed Central

Favaro, Marco; Yano, Junko; Crumlin, Ethan J.

2017-01-01

A national priority is to convert CO2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO2 in the physisorbed configuration at 298 K, and we show that this suboxide is essential for converting to the chemisorbed CO2 in the presence of water as the first step toward CO2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts. PMID:28607092

Multiple cis-acting signals, some weak by necessity, collectively direct robust transport of oskar mRNA to the oocyte.

PubMed

Ryu, Young Hee; Kenny, Andrew; Gim, Youme; Snee, Mark; Macdonald, Paul M

2017-09-15

Localization of mRNAs can involve multiple steps, each with its own cis -acting localization signals and transport factors. How is the transition between different steps orchestrated? We show that the initial step in localization of Drosophila oskar mRNA - transport from nurse cells to the oocyte - relies on multiple cis -acting signals. Some of these are binding sites for the translational control factor Bruno, suggesting that Bruno plays an additional role in mRNA transport. Although transport of oskar mRNA is essential and robust, the localization activity of individual transport signals is weak. Notably, increasing the strength of individual transport signals, or adding a strong transport signal, disrupts the later stages of oskar mRNA localization. We propose that the oskar transport signals are weak by necessity; their weakness facilitates transfer of the oskar mRNA from the oocyte transport machinery to the machinery for posterior localization. © 2017. Published by The Company of Biologists Ltd.

Why pleiotropic interventions are needed for Alzheimer's disease.

PubMed

Frautschy, Sally A; Cole, Greg M

2010-06-01

Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of beta-amyloid (Abeta) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Abeta production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Abeta peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the "prodromal" period prior to conversion to "mild cognitive impairment (MCI)." Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284-286, 2006).

Sub-500 fs electronically nonadiabatic chemical dynamics of energetic molecules from the S1 excited state: Ab initio multiple spawning study

NASA Astrophysics Data System (ADS)

Ghosh, Jayanta; Gajapathy, Harshad; Konar, Arindam; Narasimhaiah, Gowrav M.; Bhattacharya, Atanu

2017-11-01

Energetic materials store a large amount of chemical energy. Different ignition processes, including laser ignition and shock or compression wave, initiate the energy release process by first promoting energetic molecules to the electronically excited states. This is why a full understanding of initial steps of the chemical dynamics of energetic molecules from the excited electronic states is highly desirable. In general, conical intersection (CI), which is the crossing point of multidimensional electronic potential energy surfaces, is well established as a controlling factor in the initial steps of chemical dynamics of energetic molecules following their electronic excitations. In this article, we have presented different aspects of the ultrafast unimolecular relaxation dynamics of energetic molecules through CIs. For this task, we have employed ab initio multiple spawning (AIMS) simulation using the complete active space self-consistent field (CASSCF) electronic wavefunction and frozen Gaussian-based nuclear wavefunction. The AIMS simulation results collectively reveal that the ultrafast relaxation step of the best energetic molecules (which are known to exhibit very good detonation properties) is completed in less than 500 fs. Many, however, exhibit sub-50 fs dynamics. For example, nitro-containing molecules (including C-NO2, N-NO2, and O-NO2 active moieties) relax back to the ground state in approximately 40 fs through similar (S1/S0)CI conical intersections. The N3-based energetic molecule undergoes the N2 elimination process in 40 fs through the (S1/S0)CI conical intersection. Nitramine-Fe complexes exhibit sub-50 fs Fe-O and N-O bond dissociation through the respective (S1/S0)CI conical intersection. On the other hand, tetrazine-N-oxides, which are known to exhibit better detonation properties than tetrazines, undergo internal conversion in a 400-fs time scale, while the relaxation time of tetrazine is very long (about 100 ns). Many other characteristics of sub-500 fs nonadiabatic decay of energetic molecules are discussed. In the end, many unresolved issues associated with the ultrafast nonadiabatic chemical dynamics of energetic molecules are presented.

A Data-Driven, Integrated Flare Model Based on Self-Organized Criticality

NASA Astrophysics Data System (ADS)

Dimitropoulou, M.; Isliker, H.; Vlahos, L.; Georgoulis, M.

2013-09-01

We interpret solar flares as events originating in solar active regions having reached the self-organized critical state, by alternatively using two versions of an "integrated flare model" - one static and one dynamic. In both versions the initial conditions are derived from observations aiming to investigate whether well-known scaling laws observed in the distribution functions of characteristic flare parameters are reproduced after the self-organized critical state has been reached. In the static model, we first apply a nonlinear force-free extrapolation that reconstructs the three-dimensional magnetic fields from two-dimensional vector magnetograms. We then locate magnetic discontinuities exceeding a threshold in the Laplacian of the magnetic field. These discontinuities are relaxed in local diffusion events, implemented in the form of cellular-automaton evolution rules. Subsequent loading and relaxation steps lead the system to self-organized criticality, after which the statistical properties of the simulated events are examined. In the dynamic version we deploy an enhanced driving mechanism, which utilizes the observed evolution of active regions, making use of sequential vector magnetograms. We first apply the static cellular automaton model to consecutive solar vector magnetograms until the self-organized critical state is reached. We then evolve the magnetic field inbetween these processed snapshots through spline interpolation, acting as a natural driver in the dynamic model. The identification of magnetically unstable sites as well as their relaxation follow the same rules as in the static model after each interpolation step. Subsequent interpolation/driving and relaxation steps cover all transitions until the end of the sequence. Physical requirements, such as the divergence-free condition for the magnetic field vector, are approximately satisfied in both versions of the model. We obtain robust power laws in the distribution functions of the modelled flaring events with scaling indices in good agreement with observations. We therefore conclude that well-known statistical properties of flares are reproduced after active regions reach self-organized criticality. The significant enhancement in both the static and the dynamic integrated flare models is that they initiate the simulation from observations, thus facilitating energy calculation in physical units. Especially in the dynamic version of the model, the driving of the system is based on observed, evolving vector magnetograms, allowing for the separation between MHD and kinetic timescales through the assignment of distinct MHD timestamps to each interpolation step.

40 CFR 35.2202 - Step 2+3 projects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Step 2+3 projects. 35.2202 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2202 Step 2+3 projects. (a) Prior to initiating action to acquire eligible real property, a Step 2+3 grantee shall submit for...

How we flipped the medical classroom.

PubMed

Sharma, Neel; Lau, C S; Doherty, Iain; Harbutt, Darren

2015-04-01

Flipping the classroom centres on the delivery of print, audio or video based material prior to a lecture or class session. The class session is then dedicated to more active learning processes with application of knowledge through problem solving or case based scenarios. The rationale behind this approach is that teachers can spend their face-to-face time supporting students in deeper learning processes. In this paper we provide a background literature review on the flipped classroom along with a three step approach to flipping the classroom comprising implementing, enacting and evaluating this form of pedagogy. Our three step approach is based on actual experience of delivering a flipped classroom at the University of Hong Kong. This initiative was evaluated with positive results. We hope our experience will be transferable to other medical institutions.

Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study.

PubMed

Khan, Md Abdul Shafeeuulla; Ganguly, Bishwajit

2012-05-01

Oximate anions are used as potential reactivating agents for OP-inhibited AChE because of they possess enhanced nucleophilic reactivity due to the α-effect. We have demonstrated the process of reactivating the VX-AChE adduct with formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6-311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine anion is more efficient than the formoximate anion at reactivating VX-inhibited AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems to be a two-step process. The rate-determining step in the process is the initial attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps are exergonic in nature. The potential energy surface (PES) for the reaction of the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process is facilitated by the lower free energy of activation (by a factor of 1.7 kcal mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of theory. The higher free energy of activation for the reverse reactivation reaction between hydroxylamine anion and the VX-serine adduct further suggests that the hydroxylamine anion is a very good antidote agent for the reactivation process. The activation barriers calculated in solvent using the polarizable continuum model (PCM) for the reactivation of the VX-AChE adduct with hydroxylamine anion were also found to be low. The calculated results suggest that V-series compounds can be more toxic than G-series compounds, which is in accord with earlier experimental observations.

Kinematic and behavioral analyses of protective stepping strategies and risk for falls among community living older adults.

PubMed

Bair, Woei-Nan; Prettyman, Michelle G; Beamer, Brock A; Rogers, Mark W

2016-07-01

Protective stepping evoked by externally applied lateral perturbations reveals balance deficits underlying falls. However, a lack of comprehensive information about the control of different stepping strategies in relation to the magnitude of perturbation limits understanding of balance control in relation to age and fall status. The aim of this study was to investigate different protective stepping strategies and their kinematic and behavioral control characteristics in response to different magnitudes of lateral waist-pulls between older fallers and non-fallers. Fifty-two community-dwelling older adults (16 fallers) reacted naturally to maintain balance in response to five magnitudes of lateral waist-pulls. The balance tolerance limit (BTL, waist-pull magnitude where protective steps transitioned from single to multiple steps), first step control characteristics (stepping frequency and counts, spatial-temporal kinematic, and trunk position at landing) of four naturally selected protective step types were compared between fallers and non-fallers at- and above-BTL. Fallers took medial-steps most frequently while non-fallers most often took crossover-back-steps. Only non-fallers varied their step count and first step control parameters by step type at the instants of step initiation (onset time) and termination (trunk position), while both groups modulated step execution parameters (single stance duration and step length) by step type. Group differences were generally better demonstrated above-BTL. Fallers primarily used a biomechanically less effective medial-stepping strategy that may be partially explained by reduced somato-sensation. Fallers did not modulate their step parameters by step type at first step initiation and termination, instances particularly vulnerable to instability, reflecting their limitations in balance control during protective stepping. Copyright © 2016. Published by Elsevier Ltd.

A review for identification of initiating events in event tree development process on nuclear power plants

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

Riyadi, Eko H., E-mail: e.riyadi@bapeten.go.id

2014-09-30

Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logicmore » model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events.« less

Gynecomastia: Pathophysiology, Evaluation, and Management

PubMed Central

Johnson, Ruth E.; Murad, M. Hassan

2009-01-01

Gynecomastia, defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications. Although a fairly common presentation in the primary care setting and mostly of benign etiology, it can cause patients considerable anxiety. The initial step is to rule out pseudogynecomastia by careful history taking and physical examination. A stepwise approach that includes imaging and laboratory testing to exclude neoplasms and endocrinopathies may facilitate cost-effective diagnosis. If results of all studies are normal, idiopathic gynecomastia is diagnosed. The evidence in this area is mainly of observational nature and lower quality. PMID:19880691

The impact of a public health department's expansion from a one-step to a two-step refugee screening process on the detection and initiation of treatment of latent tuberculosis.

PubMed

Einterz, E M; Younge, O; Hadi, C

2018-06-01

To determine, subsequent to the expansion of a county health department's refugee screening process from a one-step to a two-step process, the change in early loss to follow-up and time to initiation of treatment of new refugees with latent tuberculosis infection (LTBI). Quasi-experimental, quantitative. Review of patient medical records. Among 384 refugees who met the case definition of LTBI without prior tuberculosis (TB) classification, the number of cases lost to early follow-up fell from 12.5% to 0% after expansion to a two-step screening process. The average interval between in-country arrival and initiation of LTBI treatment was shortened by 41.4%. The addition of a second step to the refugee screening process was correlated with significant improvements in the county's success in tracking and treating cases of LTBI in refugees. Given the disproportionate importance of foreign-born cases of LTBI to the incidence of TB disease in low-incidence countries, these improvements could have a substantial impact on overall TB control, and the process described could serve as a model for other local health department refugee screening programs. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Initiation of forward gait with lateral occurrence of emotional stimuli: general findings and relevance for pedestrians crossing roads.

PubMed

Caffier, D; Gillet, C; Heurley, L P; Bourrelly, A; Barbier, F; Naveteur, J

2017-03-01

With reference to theoretical models regarding links between emotions and actions, the present study examined whether the lateral occurrence of an emotional stimulus influences spatial and temporal parameters of gait initiation in 18 younger and 18 older healthy adults. In order to simulate road-crossing hazard for pedestrians, slides of approaching cars were used and they were presented in counterbalanced order with threatening slides from the International Affective Picture System (IAPS) and control slides of safe walking areas. Each slide was presented on the left side of the participant once the first step was initiated. The results evidenced medio-lateral shifts to the left for the first step (right foot) and to the right for the second step (left foot). These shifts were both modulated by the slide contents in such a way that the resulting distance between the screen and the foot (right or left) was larger with the IAPS and traffic slides than with the control slides. The slides did not affect the base of support, step length, step velocity and time of double support. Advancing age influenced the subjective impact of the slides and gait characteristics, but did not modulate medio-lateral shifts. The data extend evidence of fast, emotional modulation of stepping, with theoretical and applied consequences.

Hybrid method to estimate two-layered superficial tissue optical properties from simulated data of diffuse reflectance spectroscopy.

PubMed

Hsieh, Hong-Po; Ko, Fan-Hua; Sung, Kung-Bin

2018-04-20

An iterative curve fitting method has been applied in both simulation [J. Biomed. Opt.17, 107003 (2012)JBOPFO1083-366810.1117/1.JBO.17.10.107003] and phantom [J. Biomed. Opt.19, 077002 (2014)JBOPFO1083-366810.1117/1.JBO.19.7.077002] studies to accurately extract optical properties and the top layer thickness of a two-layered superficial tissue model from diffuse reflectance spectroscopy (DRS) data. This paper describes a hybrid two-step parameter estimation procedure to address two main issues of the previous method, including (1) high computational intensity and (2) converging to local minima. The parameter estimation procedure contained a novel initial estimation step to obtain an initial guess, which was used by a subsequent iterative fitting step to optimize the parameter estimation. A lookup table was used in both steps to quickly obtain reflectance spectra and reduce computational intensity. On simulated DRS data, the proposed parameter estimation procedure achieved high estimation accuracy and a 95% reduction of computational time compared to previous studies. Furthermore, the proposed initial estimation step led to better convergence of the following fitting step. Strategies used in the proposed procedure could benefit both the modeling and experimental data processing of not only DRS but also related approaches such as near-infrared spectroscopy.

Methods of Engaging Preschool-age Children in Science Practices During Astronomy Activities

NASA Astrophysics Data System (ADS)

Plummer, J. D.

2015-11-01

Providing preschool children with science learning experiences may improve their later science literacy. Further, research shows that children are capable of engaging in the same kinds of scientific reasoning as adults. An initial step towards increasing the opportunities for children to engage in science is to improve our understanding of how to support children's engagement in the practices of science in astronomy. To this end, the My Sky Tonight project is developing and evaluating astronomy activities for informal science educators to use with young children. I have gathered video of a series of astronomy workshops that engaged preschool-age children with My Sky Tonight-developed activities. This paper describes features of these museum-based astronomy activities that supported young children in evidence-based science practices.

Nucleosome occupancy as a novel chromatin parameter for replication origin functions

PubMed Central

Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio

2017-01-01

Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110

Multiple Imputation of Completely Missing Repeated Measures Data within Person from a Complex Sample: Application to Accelerometer Data in the National Health and Nutrition Examination Survey

PubMed Central

Liu, Benmei; Yu, Mandi; Graubard, Barry I; Troiano, Richard P; Schenker, Nathaniel

2016-01-01

The Physical Activity Monitor (PAM) component was introduced into the 2003-2004 National Health and Nutrition Examination Survey (NHANES) to collect objective information on physical activity including both movement intensity counts and ambulatory steps. Due to an error in the accelerometer device initialization process, the steps data were missing for all participants in several primary sampling units (PSUs), typically a single county or group of contiguous counties, who had intensity count data from their accelerometers. To avoid potential bias and loss in efficiency in estimation and inference involving the steps data, we considered methods to accurately impute the missing values for steps collected in the 2003-2004 NHANES. The objective was to come up with an efficient imputation method which minimized model-based assumptions. We adopted a multiple imputation approach based on Additive Regression, Bootstrapping and Predictive mean matching (ARBP) methods. This method fits alternative conditional expectation (ace) models, which use an automated procedure to estimate optimal transformations for both the predictor and response variables. This paper describes the approaches used in this imputation and evaluates the methods by comparing the distributions of the original and the imputed data. A simulation study using the observed data is also conducted as part of the model diagnostics. Finally some real data analyses are performed to compare the before and after imputation results. PMID:27488606

An iron-sulfur center essential for transcriptional activation by the redox-sensing SoxR protein.

PubMed Central

Hidalgo, E; Demple, B

1994-01-01

The soxRS oxidative stress regulon of Escherichia coli is triggered by superoxide (O2.-) generating agents or by nitric oxide through two consecutive steps of gene activation. SoxR protein has been proposed as the redox sensing gene activator that triggers this cascade of gene expression. We have now characterized two forms of SoxR: Fe-SoxR contained non-heme iron (up to 1.6 atoms per monomer); apo-SoxR was devoid of Fe or other metals. The spectroscopic properties of Fe-SoxR indicated that it contains a redox active iron-sulfur (FeS) cluster that is oxidized upon extraction from E. coli. Fe-SoxR and apo-SoxR bound the in vivo target, the soxS promoter, with equal affinities and protected the same region from DNase I in vitro. However, only Fe-SoxR stimulated transcription initiation at soxS in vitro > 100-fold, similar to the activation of soxS expression in vivo. This stimulation occurred at a step after the binding of RNAP and indicates a conformational effect of oxidized Fe-SoxR on the soxS promoter. The variable redox state of the SoxR FeS cluster may thus be employed in vivo to modulate the transcriptional activity of this protein in response to specific types of oxidative stress. Images PMID:8306957

How vertebrate and invertebrate visual pigments differ in their mechanism of photoactivation

PubMed Central

Nakagawa, Masashi; Iwasa, Tatsuo; Kikkawa, Satoshi; Tsuda, Motoyuki; Ebrey, Thomas G.

1999-01-01

In vertebrate visual pigments, a glutamic acid serves as a negative counterion to the positively charged chromophore, a protonated Schiff base of retinal. When photoisomerization leads to the Schiff base deprotonating, the anionic glutamic acid becomes protonated, forming a neutral species that activates the visual cascade. We show that in octopus rhodopsin, the glutamic acid has no anionic counterpart. Thus, the “counterion” is already neutral, so no protonated form of an initially anionic group needs to be created to activate. This helps to explain another observation—that the active photoproduct of octopus rhodopsin can be formed without its Schiff base deprotonating. In this sense, the mechanism of light activation of octopus rhodopsin is simpler than for vertebrates, because it eliminates one of the steps required for vertebrate rhodopsins to achieve their activating state. PMID:10339563

Dual initiation strip charge apparatus and methods for making and implementing the same

DOEpatents

Jakaboski, Juan-Carlos [Albuquerque, NM; Todd,; Steven, N [Rio Rancho, NM; Polisar, Stephen [Albuquerque, NM; Hughs, Chance [Tijeras, NM

2011-03-22

A Dual Initiation Strip Charge (DISC) apparatus is initiated by a single initiation source and detonates a strip of explosive charge at two separate contacts. The reflection of explosively induced stresses meet and create a fracture and breach a target along a generally single fracture contour and produce generally fragment-free scattering and no spallation. Methods for making and implementing a DISC apparatus provide numerous advantages over previous methods of creating explosive charges by utilizing steps for rapid prototyping; by implementing efficient steps and designs for metering consistent, repeatable, and controlled amount of high explosive; and by utilizing readily available materials.

Planning for Growth.

ERIC Educational Resources Information Center

Astle, Judy Hughes

2001-01-01

A summer camp expanded into year-round operation one step at a time. Initial steps included identifying the camp mission, history, and assets. Successive steps became larger and included expanding the program within the mission, increasing marketing efforts, developing natural resources, creating plans for maintenance and improvements, and…

Activity Monitors Step Count Accuracy in Community-Dwelling Older Adults.

PubMed

Johnson, Marquell

2015-01-01

Objective: To examine the step count accuracy of activity monitors in community-dwelling older adults. Method : Twenty-nine participants aged 67.70 ± 6.07 participated. Three pedometers and the Actical accelerometer step count functions were compared with actual steps taken during a 200-m walk around an indoor track and during treadmill walking at three different speeds. Results : There was no statistical difference between activity monitors step counts and actual steps during self-selected pace walking. During treadmill walking at 0.67 m∙s -1 , all activity monitors step counts were significantly different from actual steps. During treadmill walking at 0.894m∙s -1 , the Omron HJ-112 pedometer step counts were not significantly different from actual steps. During treadmill walking at 1.12 m∙s -1 , the Yamax SW-200 pedometer steps were significantly different from actual steps. Discussion : Activity monitor selection should be deliberate when examining the walking behaviors of community-dwelling older adults, especially for those who walk at a slower pace.

Activity Monitors Step Count Accuracy in Community-Dwelling Older Adults

PubMed Central

2015-01-01

Objective: To examine the step count accuracy of activity monitors in community-dwelling older adults. Method: Twenty-nine participants aged 67.70 ± 6.07 participated. Three pedometers and the Actical accelerometer step count functions were compared with actual steps taken during a 200-m walk around an indoor track and during treadmill walking at three different speeds. Results: There was no statistical difference between activity monitors step counts and actual steps during self-selected pace walking. During treadmill walking at 0.67 m∙s−1, all activity monitors step counts were significantly different from actual steps. During treadmill walking at 0.894m∙s−1, the Omron HJ-112 pedometer step counts were not significantly different from actual steps. During treadmill walking at 1.12 m∙s−1, the Yamax SW-200 pedometer steps were significantly different from actual steps. Discussion: Activity monitor selection should be deliberate when examining the walking behaviors of community-dwelling older adults, especially for those who walk at a slower pace. PMID:28138464

Electrification in winter storms and the analysis of thunderstorm overflight data

NASA Technical Reports Server (NTRS)

Brook, Marx

1993-01-01

We have been focusing our study of electrification in winter storms on the lightning initiation process, making inferences about the magnitude of the electric fields from the initial pulses associated with breakdown, i.e., with the formation of the initial streamers. The essence of the most significant finding is as follows: (1) initial breakdown radiation pulses from stepped leaders prior to the first return stroke are very large, reaching values of 20-30 Volts/meter, comparable to return stroke radiation; and (2) the duration of the stepped leader, from the initial detectable radiation pulse to the return stroke onset, is very-short-ranging from a minimum 1.5 ms to a maximum of 4.5 ms. This past summer (June-August of 1991) we participated in the CAPE program at the Kennedy Space Center in order to acquire data on stepped leaders in summer storms with the same equipment used to get the winter storm data. We discovered that the vigorous leaders seen in winter so frequently were present in summer storms, although not as large in amplitude and certainly not as frequent.

24 CFR Appendix E to Part 3500 - Arithmetic Steps

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Arithmetic Steps E Appendix E to...—Arithmetic Steps I. Example Illustrating Aggregate Analysis: ASSUMPTIONS: Disbursements: $360 for school... Payment: July 1 Step 1—Initial Trial Balance Aggregate pmt disb bal Jun 0 0 0 Jul 130 500 −370 Aug 130 0...

Tandem catalysis for the preparation of cylindrical polypeptide brushes.

PubMed

Rhodes, Allison J; Deming, Timothy J

2012-11-28

Here, we report a method for synthesis of cylindrical copolypeptide brushes via N-carboxyanhydride (NCA) polymerization utilizing a new tandem catalysis approach that allows preparation of brushes with controlled segment lengths in a straightforward, one-pot procedure requiring no intermediate isolation or purification steps. To obtain high-density brush copolypeptides, we used a "grafting from" approach where alloc-α-aminoamide groups were installed onto the side chains of NCAs to serve as masked initiators. These groups were inert during cobalt-initiated NCA polymerization and gave allyloxycarbonyl-α-aminoamide-substituted polypeptide main chains. The alloc-α-aminoamide groups were then activated in situ using nickel to generate initiators for growth of side-chain brush segments. This use of stepwise tandem cobalt and nickel catalysis was found to be an efficient method for preparation of high-chain-density, cylindrical copolypeptide brushes, where both the main chains and side chains can be prepared with controlled segment lengths.

Growth-dependent regulation of rRNA synthesis is mediated by a transcription initiation factor (TIF-IA).

PubMed

Buttgereit, D; Pflugfelder, G; Grummt, I

1985-11-25

Mouse RNA polymerase I requires at least two chromatographically distinct transcription factors (designated TIF-IA and TIF-IB) to initiate transcription accurately and efficiently in vitro. In this paper we describe the partial purification of TIF-IA by a four-step fractionation procedure. The amount or activity of TIF-IA fluctuates in response to the physiological state of the cells. Extracts from quiescent cells are incapable of specific transcription and do not contain detectable levels of TIF-IA. Transcriptionally inactive extracts can be restored by the addition of TIF-IA preparations that have been highly purified from exponentially growing cells. During the fractionating procedure TIF-IA co-purifies with RNA polymerase I, suggesting that it is functionally associated with the transcribing enzyme. We suggest that only those enzyme molecules that are associated with TIF-IA are capable to interact with TIF-IB and to initiate transcription.

Improving the hardness of dry granulated tablets containing sodium lauryl sulfate.

PubMed

Moore, Francis; Okelo, Geoffrey; Colón, Ivelisse; Kushner, Joseph

2010-11-15

The impact of the addition of a wetting agent, the surfactant sodium lauryl sulfate (SLS), on the tablet hardness of a dry granulated, solid oral dosage form was investigated. In three batches, SLS was added concurrently with: (1) a poorly soluble, highly hydrophobic active pharmaceutical ingredient (API) and the other excipients prior to the initial blending step, (2) magnesium stearate prior to roller compaction, or (3) magnesium stearate prior to tableting. A fourth batch, which did not contain SLS, served as a control. The maximum hardness of 100 mg, 1/4″-SRC tablets for the four batches--SLS added initially, prior to roller compaction, prior to tableting, and no SLS--were 61±3, 71±3, 89±5, and 86±3N, respectively, suggesting reduced processing of SLS improves tablet hardness by ∼50%. Dissolution of the tablets in 900 ml of simulated gastric fluid with paddles at 75 rpm showed that: (1) there was no impact on the insertion point of SLS into the process on API dissolution, and (2) that the presence of SLS improved dissolution by 5% compared to the control tablets. Adding SLS just prior to tableting can improve tablet hardness and yield similar dissolution performance relative to SLS addition prior to the initial blending step. Copyright © 2010 Elsevier B.V. All rights reserved.

Enzymology below 200 K: The kinetics and thermodynamics of the photochemistry catalyzed by protochlorophyllide oxidoreductase

PubMed Central

Heyes, Derren J.; Ruban, Alexander V.; Wilks, Helen M.; Hunter, C. Neil

2002-01-01

The chlorophyll biosynthesis enzyme protochlorophyllide reductase (POR) catalyzes the light-dependent reduction of protochlorophyllide (Pchlide) into chlorophyllide in the presence of NADPH. As POR is light-dependent, catalysis can be initiated by illumination of the enzyme-substrate complex at low temperatures, making it an attractive model for studying aspects of biological proton and hydride transfers. The early stages in the photoreduction, involving Pchlide binding and an initial photochemical reaction, have been studied in vitro by using low-temperature fluorescence and absorbance measurements. Formation of the ternary POR-NADPH-Pchlide complex produces red shifts in the fluorescence and absorbance maxima of Pchlide, allowing the dissociation constant for Pchlide binding to be measured. We demonstrate that the product of an initial photochemical reaction, which can occur below 200 K, is a nonfluorescent intermediate with a broad absorbance band at 696 nm (A696) that is suggested to represent an ion radical complex. The temperature dependence of the rate of A696 formation has allowed the activation energy for the photochemical step to be calculated and has shown that POR catalysis can proceed at much lower temperatures than previously thought. Calculations of differences in free energy between various reaction intermediates have been calculated; these, together with the quantum efficiency for Pchlide conversion, suggest a quantitative model for the thermodynamics of the light-driven step of Pchlide reduction. PMID:12177453

"A phony way to show sincerity, as we all well know": tobacco industry lobbying against tobacco control in Hong Kong

PubMed Central

Knight, J; Chapman, S

2004-01-01

Objective: To examine the tobacco industry's efforts to influence public policy and block the legislative process on tobacco control in Hong Kong, 1973 to 1997. Method: Systematic review of relevant tobacco industry documents made public via the Master Settlement Agreement. Results: The tobacco industry in Hong Kong has sought to manipulate the policymaking process and delay the introduction of tobacco control legislation in Hong Kong from at least 1973. The industry ensured that each of the government's initial meagre steps toward tobacco control were delayed and thwarted by drawn out "cooperation" followed by voluntary concessions on issues the industry regarded as minor. By the 1980s the government had became increasingly active in tobacco control and introduced a number of initiatives, resulting in some of the tightest legislative restrictions on smoking in Asia. The tobacco industry was successful in thwarting only one of these initiatives. Conclusions: Throughout the 1980s and 1990s two factors played a significant role in hindering the tobacco industry from successfully blocking policy initiatives: a growing political imperative, and an active and sophisticated tobacco control movement. Political will to promote public health and a strong tobacco control advocacy presence can enable governments to resist the enormous pressure exerted upon them by multinational tobacco companies. PMID:15564215

Effects of Alloyed Metal on the Catalysis Activity of Pt for Ethanol Partial Oxidation: Adsorption and Dehydrogenation on Pt3M (M=Pt, Ru, Sn, Re, Rh, and Pd)

PubMed Central

Xu, Zhen-Feng; Wang, Yixuan

2011-01-01

The adsorption and dehydrogenation reactions of ethanol over bimetallic clusters, Pt3M (M = Pt, Ru, Sn, Re, Rh, and Pd), have been extensively investigated with density functional theory. Both the α-hydrogen and hydroxyl adsorptions on Pt as well as on the alloyed transition metal M sites of PtM were considered as initial reaction steps. The adsorptions of ethanol on Pt and M sites of some PtM via the α-hydrogen were well established. Although the α-hydrogen adsorption on Pt site is weaker than the hydroxyl, the potential energy profiles show that the dehydrogenation via the α-hydrogen path has much lower energy barrier than that via the hydroxyl path. Generally for the α-hydrogen path the adsorption is a rate-determining-step because of rather low dehydrogenation barrier for the α-hydrogen adsorption complex (thermodynamic control), while the hydroxyl path is determined by its dehydrogenation step (kinetic control). The effects of alloyed metal on the catalysis activity of Pt for ethanol partial oxidation, including adsorption energy, energy barrier, electronic structure, and eventually rate constant were discussed. Among all of the alloyed metals only Sn enhances the rate constant of the dehydrogenation via the α-hydrogen path on the Pt site of Pt3Sn as compared with Pt alone, which interprets why the PtSn is the most active to the oxidation of ethanol. PMID:22102920

Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway

PubMed Central

Takashima, Shigeo; Adams, Katrina L.; Ortiz, Paola A.; Ying, Chong T.; Moridzadeh, Rameen; Younossi-Hartenstein, Amelia; Hartenstein, Volker

2013-01-01

In this paper we have investigated the developmental-genetic steps that shape the entero-endocrine system of Drosophila melanogaster from the embryo to the adult. The process starts in the endoderm of the early embryo where precursors of endocrine cells and enterocytes of the larval midgut, as well as progenitors of the adult midgut, are specified by a Notch signaling-dependent mechanism. In a second step that occurs during the late larval period, enterocytes and endocrine cells of a transient pupal midgut are selected from within the clusters of adult midgut progenitors. As in the embryo, activation of the Notch pathway triggers enterocyte differentiation, and inhibits cells from further proliferation or choosing the endocrine fate. The third step of entero-endocrine cell development takes place at a mid-pupal stage. Before this time point, the epithelial layer destined to become the adult midgut is devoid of endocrine cells. However, precursors of the intestinal midgut stem cells (pISCs) are already present. After an initial phase of symmetric divisions which causes an increase in their own population size, pISCs start to spin off cells that become postmitotic and express the endocrine fate marker, Prospero. Activation of Notch in pISCs forces these cells into an enterocyte fate. Loss of Notch function causes an increase in the proliferatory activity of pISCs, as well as a higher ratio of Prospero-positive cells. PMID:21382366

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers

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

Zajnulina, M.; Giannone, D.; Haynes, R.

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromaticmore » input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.« less

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers.

PubMed

Zajnulina, M; Böhm, M; Blow, K; Rieznik, A A; Giannone, D; Haynes, R; Roth, M M

2015-10-01

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromatic input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers

NASA Astrophysics Data System (ADS)

Zajnulina, M.; Böhm, M.; Blow, K.; Rieznik, A. A.; Giannone, D.; Haynes, R.; Roth, M. M.

2015-10-01

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromatic input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.

Six-Minute-Walk Distance and Accelerometry Predict Outcomes in Chronic Obstructive Pulmonary Disease Independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group

PubMed Central

Smith, Patrick J.; Babyak, Michael A.; Mabe, Stephanie K.; Martinu, Tereza; Welty-Wolf, Karen E.; Emery, Charles F.; Palmer, Scott M.; Blumenthal, James A.

2015-01-01

Rationale: The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. Objectives: To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Methods: Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Measurements and Main Results: Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P = 0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P = 0.002). Conclusions: Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD. PMID:25568929

The effect of cane use on the compensatory step following posterior perturbations.

PubMed

Hall, Courtney D; Jensen, Jody L

2004-08-01

The compensatory step is a critical component of the balance response and is impaired in older fallers. The purpose of this research was to examine whether utilization of a cane modified the compensatory step response following external posterior perturbations. Single subject withdrawal design was employed. Single subject statistical analysis--the standard deviation bandwidth-method--supplemented visual analysis of the data. Four older adults (range: 73-83 years) with balance impairment who habitually use a cane completed this study. Subjects received a series of sudden backward pulls that were large enough to elicit compensatory stepping. We examined the following variables both with and without cane use: timing of cane loading relative to step initiation and center of mass acceleration, stability margin, center of mass excursion and velocity, step length and width. No participant loaded the cane prior to initiation of the first compensatory step. There was no effect of cane use on the stability margin, nor was there an effect of cane use on center of mass excursion or velocity, or step length or width. These data suggest that cane use does not necessarily improve balance recovery following an external posterior perturbation when the individual is forced to rely on compensatory stepping. Instead these data suggest that the strongest factor in modifying step characteristics is experience with the perturbation.

THE EFFECT OF STEP RATE MANIPULATION ON FOOT STRIKE PATTERN OF LONG DISTANCE RUNNERS.

PubMed

Allen, Darrell J; Heisler, Hollie; Mooney, Jennifer; Kring, Richard

2016-02-01

Running gait retraining to change foot strike pattern in runners from a heel strike pattern to a non heel- strike pattern has been shown to reduce impact forces and may help to reduce running related injuries. Step rate manipulation above preferred is known to help decrease step length, foot inclination angle, and vertical mass excursion, but has not yet been evaluated as a method to change foot strike pattern. The purpose of this study was to investigate the effect of step rate manipulation on foot strike pattern in shod recreational runners who run with a heel strike pattern. A secondary purpose was to describe the effect of step rate manipulation at specific percentages above preferred on foot inclination angle at initial contact. Forty volunteer runners, who were self-reported heel strikers and had a weekly running mileage of at least 10 miles, were recruited. Runners were confirmed to be heel strikers during the warm up period on the treadmill. The subject's step rate was determined at their preferred running pace. A metronome was used to increase step rate above the preferred step rate by 5%, 10% and 15%. 2D video motion analysis was utilized to determine foot strike pattern and to measure foot inclination angle at initial contact for each step rate condition. There was a statistically significant change in foot strike pattern from a heel strike pattern to a mid-foot or forefoot strike pattern at both 10% and 15% step rates above preferred. Seven of the 40 subjects (17.5%) changed from a heel- strike pattern to a non- heel strike pattern at +10% and 12 of the 40 subjects (30%) changed to a non-heel strike pattern at +15%. Mean foot inclination angle at initial contact showed a statistically significant change (reduction) as step rate increased. Step rate manipulation of 10% or greater may be enough to change foot strike pattern from a heel strike to a mid-foot or forefoot strike pattern in a small percentage of recreational runners who run in traditional running shoes. If changing the foot strike pattern is the main goal, other gait re-training methods may be needed to make a change from a heel strike to a non-heel strike pattern. Step rate manipulation shows a progressive reduction of foot inclination angle at 5%, 10%, and 15% above preferred step rate which reduces the severity of the heel strike at initial contact. Step rate manipulation of at least +10% above preferred may be an effective running gait retraining method for clinicians to decrease the severity of heel strike and possibly assist a runner to change to a non-heel strike pattern. 3.

Serial changes of humor comprehension for four-frame comic Manga: an fMRI study.

PubMed

Osaka, Mariko; Yaoi, Ken; Minamoto, Takehiro; Osaka, Naoyuki

2014-07-25

Serial changes of humor comprehension evoked by a well organized four-frame comic Manga were investigated by fMRI in each step of humor comprehension. The neural substrates underlying the amusing effects in response to funny and mixed order manga were compared. In accordance with the time course of the four frames, fMRI activations changed serially. Beginning with the second frame (development scene), activation of the temporo-parietal junction (TPJ) was observed, followed by activations in the temporal and frontal areas during viewing of the third frame (turn scene). For the fourth frame (punch line), strong increased activations were confirmed in the medial prefrontal cortex (MPFC) and cerebellum. Interestingly, distinguishable activation differences in the cerebellum between funny and non-funny conditions were also found for the fourth frame. These findings suggest that humor comprehension evokes activation that initiates in the TPJ and expands to the MPFC and cerebellum at the convergence level.

Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

PubMed

Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

2005-04-26

Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

Computer Based Procedures for Field Workers - FY16 Research Activities

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

Oxstrand, Johanna; Bly, Aaron

The Computer-Based Procedure (CBP) research effort is a part of the Light-Water Reactor Sustainability (LWRS) Program, which provides the technical foundations for licensing and managing the long-term, safe, and economical operation of current nuclear power plants. One of the primary missions of the LWRS program is to help the U.S. nuclear industry adopt new technologies and engineering solutions that facilitate the continued safe operation of the plants and extension of the current operating licenses. One area that could yield tremendous savings in increased efficiency and safety is in improving procedure use. A CBP provides the opportunity to incorporate context-driven jobmore » aids, such as drawings, photos, and just-in-time training. The presentation of information in CBPs can be much more flexible and tailored to the task, actual plant condition, and operation mode. The dynamic presentation of the procedure will guide the user down the path of relevant steps, thus minimizing time spent by the field worker to evaluate plant conditions and decisions related to the applicability of each step. This dynamic presentation of the procedure also minimizes the risk of conducting steps out of order and/or incorrectly assessed applicability of steps. This report provides a summary of the main research activities conducted in the Computer-Based Procedures for Field Workers effort since 2012. The main focus of the report is on the research activities conducted in fiscal year 2016. The activities discussed are the Nuclear Electronic Work Packages – Enterprise Requirements initiative, the development of a design guidance for CBPs (which compiles all insights gained through the years of CBP research), the facilitation of vendor studies at the Idaho National Laboratory (INL) Advanced Test Reactor (ATR), a pilot study for how to enhance the plant design modification work process, the collection of feedback from a field evaluation study at Plant Vogtle, and path forward to commercialize INL’s CBP system.« less

Space availability in confined sheep during pregnancy, effects in movement patterns and use of space.

PubMed

Averós, Xavier; Lorea, Areta; Beltrán de Heredia, Ignacia; Arranz, Josune; Ruiz, Roberto; Estevez, Inma

2014-01-01

Space availability is essential to grant the welfare of animals. To determine the effect of space availability on movement and space use in pregnant ewes (Ovis aries), 54 individuals were studied during the last 11 weeks of gestation. Three treatments were tested (1, 2, and 3 m2/ewe; 6 ewes/group). Ewes' positions were collected for 15 minutes using continuous scan samplings two days/week. Total and net distance, net/total distance ratio, maximum and minimum step length, movement activity, angular dispersion, nearest, furthest and mean neighbour distance, peripheral location ratio, and corrected peripheral location ratio were calculated. Restriction in space availability resulted in smaller total travelled distance, net to total distance ratio, maximum step length, and angular dispersion but higher movement activity at 1 m2/ewe as compared to 2 and 3 m2/ewe (P<0.01). On the other hand, nearest and furthest neighbour distances increased from 1 to 3 m2/ewe (P<0.001). Largest total distance, maximum and minimum step length, and movement activity, as well as lowest net/total distance ratio and angular dispersion were observed during the first weeks (P<0.05) while inter-individual distances increased through gestation. Results indicate that movement patterns and space use in ewes were clearly restricted by limitations of space availability to 1 m2/ewe. This reflected in shorter, more sinuous trajectories composed of shorter steps, lower inter-individual distances and higher movement activity potentially linked with higher restlessness levels. On the contrary, differences between 2 and 3 m2/ewe, for most variables indicate that increasing space availability from 2 to 3 m2/ewe would appear to have limited benefits, reflected mostly in a further increment in the inter-individual distances among group members. No major variations in spatial requirements were detected through gestation, except for slight increments in inter-individual distances and an initial adaptation period, with ewes being restless and highly motivated to explore their new environment.

How we treat chronic active Epstein-Barr virus infection.

PubMed

Sawada, Akihisa; Inoue, Masami; Kawa, Keisei

2017-04-01

Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of the EBV-associated T- or NK-cell lymphoproliferative diseases, which also include hypersensitivity to mosquito bites and severe-type hydroavacciniforme. The manifestations of CAEBV are often self-limiting with minimum supportive care or only prednisolone and cyclosporine A with or without etoposide. However, allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure, without which patients with CAEBV die within several years. A severe hypercytokinemia and hemophagocytic syndrome, which may occur suddenly, often results in a fatal clinical course. At out institute, we have established a 3-step strategy, including allogeneic HSCT, for the treatment of CAEBV. Seventy-nine patients with CAEBV and related diseases have been treated to date. The 3-year overall survival rate (3y-OS) is currently 87.3 ± 4.2% after planned allogeneic HSCT. However, 3y-OS in patients with uncontrolled active disease is only 16.7 ± 10.8%. To maximize survival rates with minimized late sequelae, we recommend earlier initiation and completion of the 3-step treatment without watchful waiting. We present six illustrative and difficult cases (including severe hypercytokinemia or emergent HSCT) and discuss them together with 73 residual cases.

Specificity in endoplasmic reticulum-stress signaling in yeast entails a step-wise engagement of HAC1 mRNA to clusters of the stress sensor Ire1.

PubMed

van Anken, Eelco; Pincus, David; Coyle, Scott; Aragón, Tomás; Osman, Christof; Lari, Federica; Gómez Puerta, Silvia; Korennykh, Alexei V; Walter, Peter

2014-12-30

Insufficient protein-folding capacity in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR). In the ER lumen, accumulation of unfolded proteins activates the transmembrane ER-stress sensor Ire1 and drives its oligomerization. In the cytosol, Ire1 recruits HAC1 mRNA, mediating its non-conventional splicing. The spliced mRNA is translated into Hac1, the key transcription activator of UPR target genes that mitigate ER-stress. In this study, we report that oligomeric assembly of the ER-lumenal domain is sufficient to drive Ire1 clustering. Clustering facilitates Ire1's cytosolic oligomeric assembly and HAC1 mRNA docking onto a positively charged motif in Ire1's cytosolic linker domain that tethers the kinase/RNase to the transmembrane domain. By the use of a synthetic bypass, we demonstrate that mRNA docking per se is a pre-requisite for initiating Ire1's RNase activity and, hence, splicing. We posit that such step-wise engagement between Ire1 and its mRNA substrate contributes to selectivity and efficiency in UPR signaling.

Time resolved infrared studies of C-H bond activation by organometallics

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

Asplund, M.C.

This work describes how step-scan Fourier Transform Infrared spectroscopy and visible and near infrared ultrafast lasers have been applied to the study of the photochemical activation of C-H bonds in organometallic systems, which allow for the selective breaking of C-H bonds in alkanes. The author has established the photochemical mechanism of C-H activation by Tp{sup *}Rh(CO){sub 2}(Tp{sup *} = HB-Pz{sup *}{sub 3}, Pz = 3,5-dimethylpyrazolyl) in alkane solution. The initially formed monocarbonyl forms a weak solvent complex, which undergoes a change in Tp{sup *} ligand connectivity. The final C-H bond breaking step occurs at different time scales depending on themore » structure of the alkane. In linear solvents, the time scale is <50 ns and cyclic alkanes is {approximately}200 ps. The reactivity of the Tp{sup *}Rh(CO){sub 2} system has also been studied in aromatic solvents. Here the reaction proceeds through two different pathways, with very different time scales. The first proceeds in a manner analogous to alkanes and takes <50 ns. The second proceeds through a Rh-C-C complex, and takes place on a time scale of 1.8 {micro}s.« less

These Shoes Are Made for Walking: Sensitivity Performance Evaluation of Commercial Activity Monitors under the Expected Conditions and Circumstances Required to Achieve the International Daily Step Goal of 10,000 Steps

PubMed Central

O’Connell, Sandra; ÓLaighin, Gearóid; Kelly, Lisa; Murphy, Elaine; Beirne, Sorcha; Burke, Niall; Kilgannon, Orlaith; Quinlan, Leo R.

2016-01-01

Introduction Physical activity is a vitally important part of a healthy lifestyle, and is of major benefit to both physical and mental health. A daily step count of 10,000 steps is recommended globally to achieve an appropriate level of physical activity. Accurate quantification of physical activity during conditions reflecting those needed to achieve the recommended daily step count of 10,000 steps is essential. As such, we aimed to assess four commercial activity monitors for their sensitivity/accuracy in a prescribed walking route that reflects a range of surfaces that would typically be used to achieve the recommended daily step count, in two types of footwear expected to be used throughout the day when aiming to achieve the recommended daily step count, and in a timeframe required to do so. Methods Four commercial activity monitors were worn simultaneously by participants (n = 15) during a prescribed walking route reflective of surfaces typically encountered while achieving the daily recommended 10,000 steps. Activity monitors tested were the Garmin Vivofit ™, New Lifestyles’ NL-2000 ™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2) ™, and Fitbit One ™. Results All activity monitors tested were accurate in their step detection over the variety of different surfaces tested (natural lawn grass, gravel, ceramic tile, tarmacadam/asphalt, linoleum), when wearing both running shoes and hard-soled dress shoes. Conclusion All activity monitors tested were accurate in their step detection sensitivity and are valid monitors for physical activity quantification over the variety of different surfaces tested, when wearing both running shoes and hard-soled dress shoes, and over a timeframe necessary for accumulating the recommended daily step count of 10,000 steps. However, it is important to consider the accuracy of activity monitors, particularly when physical activity in the form of stepping activities is prescribed as an intervention in the treatment or prevention of a disease state. PMID:27167121

IGF-1-Involved Negative Feedback of NR2B NMDA Subunits Protects Cultured Hippocampal Neurons Against NMDA-Induced Excitotoxicity.

PubMed

Li, Yun; Sun, Wei; Han, Song; Li, Jianing; Ding, Shu; Wang, Wei; Yin, Yanling

2017-01-01

Insulin-like growth factor 1 (IGF-1) is a multifunctional protein involved in neuronal polarity and axonal guidance. In our previous study, it was discovered that IGF-1 alleviated 50-μM NMDA-induced excitotoxicity against neuronal autophagy via depression of NR2B p-Ser1303 activation. However, it was found that NMDA at a higher dose did not cause neuronal autophagy. And, the performance of IGF-1 under severe excitotoxicity still needs to be clarified. In this study, we observed that IGF-1 can salvage the hippocampal neurons in an autophagy-independent manner after 150-μM NMDA exposure using thiazolyl blue tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Western blot assay, and transmission electron microscopy. In addition, over-activation of post-synaptic NMDARs was found with the whole-cell patch clamp recording method. In order to explore whether there is a positive feedback way for post-synaptic NMDARs and the different pathway caused by 150 μM NMDA, the phosphorylation level of Fyn and the phosphorylation site of NR2B were investigated. It was observed that NR2B p-Tyr1472 was increased by the activation of Fyn after 150-μM NMDA exposure. When the neutralizing antibody against NR2B p-Ser1303 was added into the medium, both the activations of Fyn and NR2B p-Tyr1472 were blocked, suggesting NR2B p-Ser1303 may be the initial step of NMDA-induced excitotoxicity. In addition, since IGF-1 can block the initial step of NR2B activation, its effect is concluded to continue with the development of excitotoxicity. Overall, this study strongly indicates that the relationship between different phosphorylation sites of NR2B should be laid more emphasis on, which may be a vital target for the NR2B-involved excitotoxicity.

Students Targeting Engineering and Physical Science (STEPS) at California State University Northridge (CSUN):Activities and Outcomes 2011-2016

NASA Astrophysics Data System (ADS)

Cadavid, A. C.; Pedone, V. A.; Horn, W.; Rich, H.

2016-12-01

The specific goal of STEPS at CSUN is to increase the number bachelor's degrees in STEM majors, particularly those in engineering, computer science, mathematics and the physical sciences. Prior to STEPS, only 33% of first-time freshmen in these majors graduated from CSUN within 6-7 years. We employ two main strategies: 1) fostering success in lower-division mathematics for freshmen and sophomores, 2) Summer Interdisciplinary Team Experience (SITE) for students transitioning to junior level courses. To improve success in mathematics, we have advanced initial placements in the foundational mathematics sequence by one or two semesters through improvements in the placement test (6-7% improvement) and have increased the first-time pass rate in foundational math courses through mandatory supplementary laboratories for at-risk students. Students who successfully complete the supplemental laboratories pass the lecture class at a higher rate than the total population of at-risk students (65% compared to 61%). Both approaches have been institutionalized. SITE targets students entering their junior years in a 3-week interdisciplinary team project that highlights problem solving and hands-on activities. Survey results of the 233 participants show that SITE: 1) maintained or increased desire to earn a STEM degree, 2) increased positive attitudes toward team-based problem solving, 3) increased understanding in how they will use their major in a career, and 4) increased interest in faculty-mentored research and industry internships. Our 5-year program is nearing completion and shows success in meeting our goal. We have measured a 9% point increase in the pass rate of Calculus I for post-STEPS cohorts compared to pre-STEPS cohorts. Failure to pass Calculus is a leading cause in non-completion of the majors targeted by STEPS. We have analyzed the graduation rates of two pre-STEPS cohorts that have had over 6 years to graduate. Both have a graduate rate of 28%. We expect that the 9% point increase in calculus passers will lead to a comparable increase in graduation rate, resulting in a 37% graduation rate for the post-STEPS cohorts.

Hypoxia Regulates mTORC1-Mediated Keratinocyte Motility and Migration via the AMPK Pathway

PubMed Central

Yan, Tiantian; Zhang, Junhui; Tang, Di; Zhang, Xingyue; Jiang, Xupin; Zhao, Liping; Zhang, Qiong; Zhang, Dongxia; Huang, Yuesheng

2017-01-01

Keratinocyte migration, the initial event and rate-limiting step in wound healing, plays a vital role in restoration of the intact skin barrier, also known as re-epithelialization. After acute tissue injury, hypoxic microenvironment gradually develops and acts as an early stimulus to initiate the healing process. Although we have previously found that hypoxia induces keratinocyte migration, the underlying mechanism remains unknown. Here, we first observed that hypoxia increased mTORC1 activity. Recombinant lentivirus vector and Rapamycin were used for silencing mTORC1 in HaCaT cells and primary mouse keratinocytes (MKs). Using cell migration assay and a Zeiss chamber equipped with imaging system, we also demonstrated that mTORC1 downregulation reversed hypoxia-induced keratinocyte motility and lateral migration. Importantly, hypoxia-activated mTORC1 was accompanied by the AMPK downregulation, and we found that the AMPK pathway activators Metformin (Met) and 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) decreased the mTORC1 activity, cell motility and lateral migration. Thus, our results suggest that hypoxia regulates mTORC1-mediated keratinocyte motility and migration via the AMPK pathway. PMID:28068384

Constitutive activation of a plasma membrane H(+)-ATPase prevents abscisic acid-mediated stomatal closure.

PubMed

Merlot, Sylvain; Leonhardt, Nathalie; Fenzi, Francesca; Valon, Christiane; Costa, Miguel; Piette, Laurie; Vavasseur, Alain; Genty, Bernard; Boivin, Karine; Müller, Axel; Giraudat, Jérôme; Leung, Jeffrey

2007-07-11

Light activates proton (H(+))-ATPases in guard cells, to drive hyperpolarization of the plasma membrane to initiate stomatal opening, allowing diffusion of ambient CO(2) to photosynthetic tissues. Light to darkness transition, high CO(2) levels and the stress hormone abscisic acid (ABA) promote stomatal closing. The overall H(+)-ATPase activity is diminished by ABA treatments, but the significance of this phenomenon in relationship to stomatal closure is still debated. We report two dominant mutations in the OPEN STOMATA2 (OST2) locus of Arabidopsis that completely abolish stomatal response to ABA, but importantly, to a much lesser extent the responses to CO(2) and darkness. The OST2 gene encodes the major plasma membrane H(+)-ATPase AHA1, and both mutations cause constitutive activity of this pump, leading to necrotic lesions. H(+)-ATPases have been traditionally assumed to be general endpoints of all signaling pathways affecting membrane polarization and transport. Our results provide evidence that AHA1 is a distinct component of an ABA-directed signaling pathway, and that dynamic downregulation of this pump during drought is an essential step in membrane depolarization to initiate stomatal closure.

From good ideas to actions: a model-driven community collaborative to prevent childhood obesity.

PubMed

Huberty, Jennifer L; Balluff, Mary; O'Dell, Molly; Peterson, Kerri

2010-01-01

Activate Omaha Kids, a community collaborative, was designed, implemented, and evaluated with the aim of preventing childhood obesity in the Omaha community. Activate Omaha Kids brought together key stakeholders and community leaders to create a community coalition. The coalition's aim was to oversee a long-term sustainable approach to preventing obesity. Following a planning phase, a business plan was developed that prioritized best practices to be implemented in Omaha. The business plan was developed using the Ecological Model, Health Policy Model, and Robert Wood Johnson Foundation Active Living by Design 5P model. The three models helped the community identify target populations and activities that then created a single model for sustainable change. Twenty-four initiatives were identified, over one million dollars in funding was secured, and evaluation strategies were identified. By using the models from the initial steps through evaluation, a clear facilitation of the process was possible, and the result was a comprehensive, feasible plan. The use of the models to design a strategic plan was pivotal in building a sustainable coalition to achieve measurable improvements in the health of children and prove replicable over time.

New Reduced Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2004-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes that are being developed at Glenn. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting properties of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates were then used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx were obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

Geoscientific Site Evaluation Approach for Canada's Deep Geological Repository for Used Nuclear Fuel

NASA Astrophysics Data System (ADS)

Sanchez-Rico Castejon, M.; Hirschorn, S.; Ben Belfadhel, M.

2015-12-01

The Nuclear Waste Management Organization (NWMO) is responsible for implementing Adaptive Phased Management, the approach selected by the Government of Canada for long-term management of used nuclear fuel generated by Canadian nuclear reactors. The ultimate objective of APM is the centralized containment and isolation of Canada's used nuclear fuel in a Deep Geological Repository in a suitable crystalline or sedimentary rock formation. In May 2010, the NWMO published and initiated a nine-step site selection process to find an informed and willing community to host a deep geological repository for Canada's used nuclear fuel. The site selection process is designed to address a broad range of technical and social, economic and cultural factors. The site evaluation process includes three main technical evaluation steps: Initial Screenings; Preliminary Assessments; and Detailed Site Characterizations, to assess the suitability of candidate areas in a stepwise manner over a period of many years. By the end of 2012, twenty two communities had expressed interest in learning more about the project. As of July 2015, nine communities remain in the site selection process. To date (July 2015), NWMO has completed Initial Screenings for the 22 communities that expressed interest, and has completed the first phase of Preliminary Assessments (desktop) for 20 of the communities. Phase 2 of the Preliminary Assessments has been initiated in a number of communities, with field activities such as high-resolution airborne geophysical surveys and geological mapping. This paper describes the approach, methods and criteria being used to assess the geoscientific suitability of communities currently involved in the site selection process.

Calibration and validation of wearable monitors.

PubMed

Bassett, David R; Rowlands, Alex; Trost, Stewart G

2012-01-01

Wearable monitors are increasingly being used to objectively monitor physical activity in research studies within the field of exercise science. Calibration and validation of these devices are vital to obtaining accurate data. This article is aimed primarily at the physical activity measurement specialist, although the end user who is conducting studies with these devices also may benefit from knowing about this topic. Initially, wearable physical activity monitors should undergo unit calibration to ensure interinstrument reliability. The next step is to simultaneously collect both raw signal data (e.g., acceleration) from the wearable monitors and rates of energy expenditure, so that algorithms can be developed to convert the direct signals into energy expenditure. This process should use multiple wearable monitors and a large and diverse subject group and should include a wide range of physical activities commonly performed in daily life (from sedentary to vigorous). New methods of calibration now use "pattern recognition" approaches to train the algorithms on various activities, and they provide estimates of energy expenditure that are much better than those previously available with the single-regression approach. Once a method of predicting energy expenditure has been established, the next step is to examine its predictive accuracy by cross-validating it in other populations. In this article, we attempt to summarize the best practices for calibration and validation of wearable physical activity monitors. Finally, we conclude with some ideas for future research ideas that will move the field of physical activity measurement forward.

Reduced-order aeroelastic model for limit-cycle oscillations in vortex-dominated unsteady airfoil flows

NASA Astrophysics Data System (ADS)

Suresh Babu, Arun Vishnu; Ramesh, Kiran; Gopalarathnam, Ashok

2017-11-01

In previous research, Ramesh et al. (JFM,2014) developed a low-order discrete vortex method for modeling unsteady airfoil flows with intermittent leading edge vortex (LEV) shedding using a leading edge suction parameter (LESP). LEV shedding is initiated using discrete vortices (DVs) whenever the Leading Edge Suction Parameter (LESP) exceeds a critical value. In subsequent research, the method was successfully employed by Ramesh et al. (JFS, 2015) to predict aeroelastic limit-cycle oscillations in airfoil flows dominated by intermittent LEV shedding. When applied to flows that require large number of time steps, the computational cost increases due to the increasing vortex count. In this research, we apply an amalgamation strategy to actively control the DV count, and thereby reduce simulation time. A pair each of LEVs and TEVs are amalgamated at every time step. The ideal pairs for amalgamation are identified based on the requirement that the flowfield in the vicinity of the airfoil is least affected (Spalart, 1988). Instead of placing the amalgamated vortex at the centroid, we place it at an optimal location to ensure that the leading-edge suction and the airfoil bound circulation are conserved. Results of the initial study are promising.

Electroless silver plating on PET fabric initiated by in situ reduction of polyaniline

NASA Astrophysics Data System (ADS)

Mu, Shipeng; Xie, Huayang; Wang, Wei; Yu, Dan

2015-10-01

Novel electroless silver plating poly(ethylene terephthalate) (PET) fabric was prepared by a two-step procedure. In the first step, the in situ polymerized polyaniline (PANI) occurred on the fabric surface in the presence of ammonium persulfate (APS). Then, Ag(0) species reduced from silver nitrate (AgNO3) by in situ reduction of PANI were used as catalyst to initiate electroless silver plating. Hence, this composite material was prepared by conductive polymer combined with electroless plating. The silver layer on PET fabric surface was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive spectroscopy (EDX) as well as X-ray photoelectron spectroscopy (XPS). The results showed that the silver layer was plated uniformly and compactly with surface resistance about 0.1 Ω/sq on average. The shielding effectiveness (SE) of silver-plated PET fabric was around 50-90 dB, which was considered to have potential applications in electromagnetic shielding materials. Thermogravimetric (TG) analysis was carried out to study thermal stability. The antibacterial tests demonstrated that the silver-plated fabric exhibited excellent antibacterial activity against Staphylococcus aureus and Escherichia coli both with 100%.

Ankle mechanics during sidestep cutting implicates need for 2-degrees of freedom powered ankle-foot prostheses.

PubMed

Ficanha, Evandro M; Rastgaar, Mohammad; Kaufman, Kenton R

2015-01-01

The ankle joint of currently available powered prostheses is capable of controlling one degree of freedom (DOF), focusing on improved mobility in the sagittal plane. To increase agility, the requirements of turning in prosthesis design need to be considered. Ankle kinematics and kinetics were studied during sidestep cutting and straight walking. There were no significant differences between the ankle sagittal plane mechanics when comparing sidestep cutting and straight walking; however, significant differences were observed in ankle frontal plane mechanics. During straight walking, the inversion-eversion (IE) angles were smaller than with sidestep cutting. The ankle that initiated the sidestep cutting showed progressively increasing inversion from 2 to 13 degrees while the following contralateral step showed progressively decreasing inversion from 8 to -4 degrees during normal walking speed. The changes in IE kinematics were the most significant during sidestep cutting compared with straight walking. The IE moments of the step that initiated the sidestep cutting were always in eversion, acting as a braking moment opposing the inverting motion. This suggests that an ankle-foot prosthesis with active DOFs in the sagittal and frontal planes will increase the agility of gait for patients with limb loss.

Why a mosquito leg possesses superior load-bearing capacity on water: Experimentals

NASA Astrophysics Data System (ADS)

Kong, Xiang-Qing; Liu, Jian-Lin; Wu, Cheng-Wei

2016-04-01

Mosquitoes possess the striking ability to walk on water because each of their legs has a huge water supporting force (WSF) that is 23 times their body weight. Aiming at a full understanding of the origins of this extremely large force, in this study, we concentrate on two aspects of it: the intrinsic properties of the leg surface and the active control of the initial stepping angle of the whole leg. Using a measurement system that we developed ourselves, the WSFs for the original leg samples are compared with those whose surface wax and microstructures have been removed and with those of a different stiffness. The results show that leg flexibility plays a dominant role over surface wax and microstructures on the leg surface in creating the supporting force. Moreover, we discuss the dependence relationship between the maximum WSF and the initial stepping angle, which indicates that the mosquito can regulate this angle to increase or decrease the WSF during landing or takeoff. These findings are helpful for uncovering the locomotion mechanism of aquatic insects and for providing inspiration for the design of microfluids, miniature boats, biomimetic robots, and microsensors.

Mechanistic insights into the dehalogenation reaction of fluoroacetate/fluoroacetic acid

NASA Astrophysics Data System (ADS)

Miranda-Rojas, Sebastián; Toro-Labbé, Alejandro

2015-05-01

Fluoroacetate is a toxic compound whose environmental accumulation may represent an important contamination problem, its elimination is therefore a challenging issue. Fluoroacetate dehalogenase catalyzes its degradation through a two step process initiated by an SN2 reaction in which the aspartate residue performs a nucleophilic attack on the carbon bonded to the fluorine; the second step is hydrolysis that releases the product as glycolate. In this paper, we present a study based on density functional theory calculations of the SN2 initiation reaction modeled through the interaction between the substrate and the propionate anion as the nucleophile. Results are analyzed within the framework of the reaction force and using the reaction electronic flux to identify and characterize the electronic activity that drives the reaction. Our results reveal that the selective protonation of the substrate catalyzes the reaction by decreasing the resistance of the structural and electronic reorganization needed to reach the transition state. Finally, the reaction energy is modulated by the degree of stabilization of the fluoride anion formed after the SN2 reaction. In this way, a site-induced partial protonation acts as a chemical switch in a key process that determines the output of the reaction.

Metabolic fate of desomorphine elucidated using rat urine, pooled human liver preparations, and human hepatocyte cultures as well as its detectability using standard urine screening approaches.

PubMed

Richter, Lilian H J; Kaminski, Yeda Rumi; Noor, Fozia; Meyer, Markus R; Maurer, Hans H

2016-09-01

Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin. It is a crude synthesis product homemade from codeine with toxic byproducts. The aim of the present work was to investigate the metabolic fate of desomorphine in vivo using rat urine and in vitro using pooled human liver microsomes and cytosol as well as human liver cell lines (HepG2 and HepaRG) by Orbitrap-based liquid chromatography-high resolution-tandem mass spectrometry or hydrophilic interaction liquid chromatography. According to the identified metabolites, the following metabolic steps could be proposed: N-demethylation, hydroxylation at various positions, N-oxidation, glucuronidation, and sulfation. The cytochrome P450 (CYP) initial activity screening revealed CYP3A4 to be the only CYP involved in all phase I steps. UDP-glucuronyltransferase (UGT) initial activity screening showed that UGT1A1, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17 formed desomorphine glucuronide. Among the tested in vitro models, HepaRG cells were identified to be the most suitable tool for prediction of human hepatic phase I and II metabolism of drugs of abuse. Finally, desomorphine (crocodile) consumption should be detectable by all standard urine screening approaches mainly via the parent compound and/or its glucuronide assuming similar kinetics in rats and humans.

Methanol decomposition reactions over a boron-doped graphene supported Ru-Pt catalyst.

PubMed

Damte, Jemal Yimer; Lyu, Shang-Lin; Leggesse, Ermias Girma; Jiang, Jyh Chiang

2018-04-04

The decomposition of methanol is currently attracting research attention due to the potential widespread applications of its end products. In this work, density functional theory (DFT) calculations have been performed to investigate the adsorption and decomposition of methanol on a Ru-Pt/boron doped graphene surface. We find that the most favorable reaction pathway is methanol (CH3OH) decomposition through O-H bond breaking to form methoxide (CH3O) as the initial step, followed by further dehydrogenation steps which generate formaldehyde (CH2O), formyl (CHO), and carbon monoxide (CO). The calculations illustrate that CH3OH and CO groups prefer to adsorb at the Ru-top sites, while CH2OH, CH3O, CH2O, CHO, and H2 groups favor the Ru-Pt bridge sites, indicating the preference of Ru atoms to adsorb the active intermediates or species having lone-pair electrons. Based on the results, it is found that the energy barrier for CH3OH decomposition through the initial O-H bond breaking is less than its desorption energy of 0.95 eV, showing that CH3OH prefers to undergo decomposition to CH3O rather than direct desorption. The study provides in-depth theoretical insights into the potentially enhanced catalytic activity of Ru-Pt/boron doped graphene surfaces for methanol decomposition reactions, thereby contributing to the understanding and designing of an efficient catalyst under optimum conditions.

31P and 13C NMR analyses of the energy metabolism of the thermophilic anaerobe Clostridium thermocellum.

PubMed

Tolman, C J; Kanodia, S; Roberts, M F

1987-08-15

The energy metabolism of an anaerobic obligate thermophile, Clostridium thermocellum, has been examined as a function of incubation temperature using 31P NMR spectroscopy. Specifically investigated were the generation and availability of ATP as a function of temperature, activation energies for key processes in energy metabolism including formation of a pH gradient across the cell membrane, transport of key nutrients, and initial steps in glycolysis, and the existence of a membrane phase transition in the intact organism. Cells generate ATP via glycolysis at all temperatures examined; hence, limitation of the energy supply is not directly responsible for the lack of growth of this organism at low temperatures. Estimations of activation energies show a distinct hierarchy in the ATP-utilizing reactions examined. Conservation of ATP hydrolysis energy as delta pH has the lowest activation energy (less than or equal to 4 kcal/mol), two transport processes exhibit 10 kcal/mol activation energies, and early phosphorylation steps in glycolysis have significantly higher activation energies (approximately 25 kcal/mol). Neither the membrane-bound ATPase responsible for formation of the pH gradient nor the permease involved in phosphate transport shows evidence of a change in behavior around the phase transition temperature determined for extracted lipids of C. thermocellum. Line widths of inorganic phosphate do show a break in behavior around 35-40 degrees C. Possible explanations for this behavior are discussed.

[Molecular mechanisms of protein biosynthesis initiation--biochemical and biomedical implications of a new model of translation enhanced by the RNA hypoxia response element (rHRE)].

PubMed

Master, Adam; Nauman, Alicja

2014-01-01

Translation initiation is a key rate-limiting step in cellular protein synthesis. A cap-dependent initiation is the most effective mechanism of the translation. However, some physiological (mitosis) and pathological (oxidative stress) processes may switch the classic mechanism to an alternative one that is regulated by an mRNA element such as IRES, uORF, IRE, CPE, DICE, AURE or CITE. A recently discovered mechanism of RNA hypoxia response element (rHRE)-dependent translation initiation, may change the view of oxygen-regulated translation and give a new insight into unexplained biochemical processes. Hypoxia is one of the better-known factors that may trigger an alternative mechanism of the translation initiation. Temporal events of oxygen deficiency within tissues and organs may activate processes such as angiogenesis, myogenesis, regeneration, wound healing, and may promote an adaptive response in cardiovascular and neurodegenerative diseases. On the other hand, growth of solid tumors may be accompanied by cyclic hypoxia, allowing for synthesis of proteins required for further progression of cancer cells. This paper provides a review of current knowledge on translational control in the context of alternative models of translation initiation.

Triggered lightning strikes to aircraft and natural intracloud discharges

NASA Technical Reports Server (NTRS)

Mazur, Vladislav

1989-01-01

The physical model of Mazur (1989) for triggering lightning strikes by aircraft was used to interpret the initiation of intracloud flashes observed by the French UHF-VHF interferometric system. It is shown that both the intracloud discharges and airplane-triggered lightning strikes were initiated by simultaneous bidirectional development of the negative stepped leader and the positive leader-continous current process. However, the negative stepped leader phase in triggered flashes is of shorter duration (tens of milliseconds), than that in intracloud flashes (usually hundreds of milliseconds). This is considered to be due to the fact that, on the aircraft there is a single initiation process, versus the numerous initiation processes that occur inside the cloud.

Total Synthesis of Spirotenuipesines A and B

PubMed Central

2008-01-01

Spirotenuipesines A and B, isolated from the entomopathogenic fungus Paecilomyces tenuipes by Oshima and co-workers, have been synthesized. The synthesis features the highly stereoselective construction of two vicinal all-carbon quaternary centers (C5 and C6) via an intramolecular cyclopropanation/radical initiated fragmentation sequence and a diastereoselective intermolecular Diels−Alder reaction between α-methylenelactone dienophile 20 and synergistic diene 6a. Installation of the C9 tertiary alcohol occurred via nucleophilic methylation. An RCM reaction to produce a tetrasubstituted double bond in the presence of free allylic alcohol and homoallylic oxygenated functional group is also described. This route shortened the synthesis of 11 from 9 steps to 3 steps. We have further developed a strategy to gain access to optically active spirotenuipesines A and B through the synthesis of enantioenriched 10 from commercially available R-(−)-epichlorohydrin. PMID:18973385

Plasmodium vivax Malaria in Cambodia

PubMed Central

Siv, Sovannaroth; Roca-Feltrer, Arantxa; Vinjamuri, Seshu Babu; Bouth, Denis Mey; Lek, Dysoley; Rashid, Mohammad Abdur; By, Ngau Peng; Popovici, Jean; Huy, Rekol; Menard, Didier

2016-01-01

The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed. PMID:27708187

AMO EXPRESS: A Command and Control Experiment for Crew Autonomy

NASA Technical Reports Server (NTRS)

Stetson, Howard K.; Frank, Jeremy; Cornelius, Randy; Haddock, Angie; Wang, Lui; Garner, Larry

2015-01-01

NASA is investigating a range of future human spaceflight missions, including both Mars-distance and Near Earth Object (NEO) targets. Of significant importance for these missions is the balance between crew autonomy and vehicle automation. As distance from Earth results in increasing communication delays, future crews need both the capability and authority to independently make decisions. However, small crews cannot take on all functions performed by ground today, and so vehicles must be more automated to reduce the crew workload for such missions. NASA's Advanced Exploration Systems Program funded Autonomous Mission Operations (AMO) project conducted an autonomous command and control demonstration of intelligent procedures to automatically initialize a rack onboard the International Space Station (ISS) with power and thermal interfaces, and involving core and payload command and telemetry processing, without support from ground controllers. This autonomous operations capability is enabling in scenarios such as a crew medical emergency, and representative of other spacecraft autonomy challenges. The experiment was conducted using the Expedite the Processing of Experiments for Space Station (EXPRESS) rack 7, which was located in the Port 2 location within the U.S Laboratory onboard the International Space Station (ISS). Activation and deactivation of this facility is time consuming and operationally intensive, requiring coordination of three flight control positions, 47 nominal steps, 57 commands, 276 telemetry checks, and coordination of multiple ISS systems (both core and payload). The autonomous operations concept includes a reduction of the amount of data a crew operator is required to verify during activation or de-activation, as well as integration of procedure execution status and relevant data in a single integrated display. During execution, the auto-procedures provide a step-by-step messaging paradigm and a high level status upon termination. This messaging and high level status is the only data generated for operator display. To enhance situational awareness of the operator, the Web-based Procedure Display (WebPD) provides a novel approach to the issues of procedure display and execution tracking. For this demonstration, the procedure was initiated and monitored from the ground. As the Timeliner sequences executed, their high level execution status was transmitted to ground, for WebPD consumption.

Pregnant & Lactating Mothers' Attitudes and Practice of the Ten Steps to Successful Breastfeeding at King Fahd Hospital of University (KFHU)--Khobar, Saudi Arabia: Appraisal of Baby Friendly Hospital Initiatives

ERIC Educational Resources Information Center

Salem, Laila Younis Abu; Al Madani, Maha Mohammed

2015-01-01

Background: World Health organization (WHO) and the United Nations Children's Fund (UNICEF) have been recommended the application of the Ten Steps to Successful Breastfeeding of the Baby-Friendly Hospital Initiative (BFHI) in order to promote & support breastfeeding. The aim of this study was to assess pregnant and lactating mothers' attitudes…

Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Prober, R. J.; de Guzman, C. P.; de Leon, R.

1992-01-01

The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its ability to execute full weight-supporting locomotion on a treadmill belt.

Client-centered counseling improves client satisfaction with family planning visits: evidence from Irbid, Jordan

PubMed Central

Kamhawi, Sarah; Underwood, Carol; Murad, Huda; Jabre, Bushra

2013-01-01

ABSTRACT Background: High levels of unmet need for family planning and high contraceptive discontinuation rates persist in Jordan, prompting the Jordan Health Communication Partnership (JHCP) to initiate a client-centered family planning service program called “Consult and Choose” (CC), together with community-based activities to encourage women with unmet need to visit health centers. Methods: We held exit interviews with 461 family planning clients between November–December 2011 to assess, from the clients' perspective, whether trained providers followed the CC protocol and used the CC tools, as well as to measure client satisfaction. We also tracked referral card information from community-based activities to health centers and examined service statistics to explore trends in family planning use. Results: On average, clients reported that providers performed 5.6 of the 7 steps outlined in the CC protocol. Nearly 83% of respondents were very satisfied with their clinic visits. Logistic regression analysis found that the odds of being “very satisfied” increases by 20% with each additional counseling protocol step performed and by 70% with each increase in the number of CC materials used. Between June 2011 and August 2012, 14,490 referral cards from community-based activities were collected in health centers, 59% of which were for family planning services. Service statistic trends indicate an increase in the number of new family planning users and in couple-years of protection after starting the CC program. Conclusions: Implementation of the CC program at health centers nationally, in tandem with community-based interventions, could play a key role in attaining Jordan's goal of reducing its total fertility rate to 2.1 by 2030. Although this initiative would likely be replicated most readily in other middle-income countries, lower-resource countries could also adapt the tested CC approach. PMID:25276531

Efficient hyperspectral image segmentation using geometric active contour formulation

NASA Astrophysics Data System (ADS)

Albalooshi, Fatema A.; Sidike, Paheding; Asari, Vijayan K.

2014-10-01

In this paper, we present a new formulation of geometric active contours that embeds the local hyperspectral image information for an accurate object region and boundary extraction. We exploit self-organizing map (SOM) unsupervised neural network to train our model. The segmentation process is achieved by the construction of a level set cost functional, in which, the dynamic variable is the best matching unit (BMU) coming from SOM map. In addition, we use Gaussian filtering to discipline the deviation of the level set functional from a signed distance function and this actually helps to get rid of the re-initialization step that is computationally expensive. By using the properties of the collective computational ability and energy convergence capability of the active control models (ACM) energy functional, our method optimizes the geometric ACM energy functional with lower computational time and smoother level set function. The proposed algorithm starts with feature extraction from raw hyperspectral images. In this step, the principal component analysis (PCA) transformation is employed, and this actually helps in reducing dimensionality and selecting best sets of the significant spectral bands. Then the modified geometric level set functional based ACM is applied on the optimal number of spectral bands determined by the PCA. By introducing local significant spectral band information, our proposed method is capable to force the level set functional to be close to a signed distance function, and therefore considerably remove the need of the expensive re-initialization procedure. To verify the effectiveness of the proposed technique, we use real-life hyperspectral images and test our algorithm in varying textural regions. This framework can be easily adapted to different applications for object segmentation in aerial hyperspectral imagery.

Optochemical Control of Protein Localization and Activity within Cell-like Compartments.

PubMed

Caldwell, Reese M; Bermudez, Jessica G; Thai, David; Aonbangkhen, Chanat; Schuster, Benjamin S; Courtney, Taylor; Deiters, Alexander; Hammer, Daniel A; Chenoweth, David M; Good, Matthew C

2018-05-08

We report inducible dimerization strategies for controlling protein positioning, enzymatic activity, and organelle assembly inside synthetic cell-like compartments upon photostimulation. Using a photocaged TMP-Haloligand compound, we demonstrate small molecule and light-induced dimerization of DHFR and Haloenzyme to localize proteins to a compartment boundary and reconstitute tripartite sfGFP assembly. Using photocaged rapamycin and fragments of split TEV protease fused to FRB and FKBP, we establish optical triggering of protease activity inside cell-size compartments. We apply light-inducible protease activation to initiate assembly of membraneless organelles, demonstrating the applicability of these tools for characterizing cell biological processes in vitro. This modular toolkit, which affords spatial and temporal control of protein function in a minimal cell-like system, represents a critical step toward the reconstitution of a tunable synthetic cell, built from the bottom up.

KSC-2014-2737

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Kennedy Space Center Director Bob Cabana, right, Florida State Surgeon General John Armstrong and other guests prepare for an early morning run at the center's Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

KSC-2014-2740

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Kennedy Space Center Director Bob Cabana, right, and Florida State Surgeon General John Armstrong begin an early morning run along the center's Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

KSC-2014-2739

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Kennedy Space Center Director Bob Cabana, right, shakes hands with Florida State Surgeon General John Armstrong before an early morning run along the center's Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

KSC-2014-2745

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Kennedy Space Center Director Bob Cabana, left, and Florida State Surgeon General John Armstrong complete an early morning run along the center's Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

KSC-2014-2741

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Nancy Bray, right, Center Operations director at Kennedy Space Center, and Lori Hicks, Human Resources, take an early morning walk along the center's Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

KSC-2014-2743

NASA Image and Video Library

2014-05-19

CAPE CANAVERAL, Fla. – Kennedy Space Center Director Bob Cabana, right, and Florida State Surgeon General John Armstrong take an early morning run along the center's Pathfinder Trail near the Operations and Support Building II at Kennedy Space Center in Florida, to officially kick off National Employee Health and Fitness Month with the NASA Moves! challenge. NASA Moves! challenged the workforce from each of the agency's field centers to engage in at least 20 minutes of activity, or 10,000 steps, each day from May 18-31. About 100 people participated in the kickoff event on the Pathfinder Trail in the heart of the center's Launch Complex 39. The one-third-mile-long gravel walkway traces the iconic shape of a space shuttle orbiter and features a set of exercise stations. The friendly contest is part of NASA's new Health4Life initiative, a Web-based health initiative designed to help employees track their health, fitness and nutrition. Health4Life also provides an array of resources geared toward increasing physical activity. Photo credit: NASA/Dimitri Gerondidakis

Sequential solar photo-fenton-biological system for the treatment of winery wastewaters.

PubMed

Mosteo, R; Sarasa, J; Ormad, Maria P; Ovelleiro, J L

2008-08-27

In this study, winery wastewaters are considered for degradation using heterogeneous photo-Fenton as a preliminary step before biotreatment. The heterogeneous photo-Fenton process assisted by solar light is able to partially degrade the organic matter present in winery wastewaters. When an initial hydrogen peroxide concentration of 0.1 M is used over 24 h of treatment, a degradation yield of organic matter (measured as TOC) of around 50% is reached. The later treatment (activated sludge process) allows the elimination of 90% of the initial TOC present in pretreated winery wastewaters without producing nondesired side-effects, such as the bulking phenomenon, which is usually detected when this treatment is used alone. The final effluent contains a concentration of organic matter (measured as COD) of 128 mg O2/L. The coupled system comprising the heterogeneous photo-Fenton process and biological treatment based on activated sludge in simple stage is a real alternative for the treatment of winery wastewater.

The time course of saccadic decision making: dynamic field theory.

PubMed

Wilimzig, Claudia; Schneider, Stefan; Schöner, Gregor

2006-10-01

Making a saccadic eye movement involves two decisions, the decision to initiate the saccade and the selection of the visual target of the saccade. Here we provide a theoretical account for the time-courses of these two processes, whose instabilities are the basis of decision making. We show how the cross-over from spatial averaging for fast saccades to selection for slow saccades arises from the balance between excitatory and inhibitory processes. Initiating a saccade involves overcoming fixation, as can be observed in the countermanding paradigm, which we model accounting both for the temporal evolution of the suppression probability and its dependence on fixation activity. The interaction between the two forms of decision making is demonstrated by predicting how the cross-over from averaging to selection depends on the fixation stimulus in gap-step-overlap paradigms. We discuss how the activation dynamics of our model may be mapped onto neuronal structures including the motor map and the fixation cells in superior colliculus.

IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2α Kinase GCN2 in the modulation of Neurite Outgrowth*

PubMed Central

Roffé, Martín; Hajj, Glaucia N. M.; Azevedo, Hátylas F.; Alves, Viviane S.; Castilho, Beatriz A.

2013-01-01

The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system. PMID:23447528

IMPACT is a developmentally regulated protein in neurons that opposes the eukaryotic initiation factor 2α kinase GCN2 in the modulation of neurite outgrowth.

PubMed

Roffé, Martín; Hajj, Glaucia N M; Azevedo, Hátylas F; Alves, Viviane S; Castilho, Beatriz A

2013-04-12

The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system.

Raindrops of synaptic noise on dual excitability landscape: an approach to astrocyte network modelling

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Postnov, Dmitry E.; Verveyko, Darya V.; Brazhe, Alexey R.

2018-04-01

The most abundant non-neuronal cells in the brain, astrocytes, populate all parts of the central nervous system (CNS). Astrocytic calcium activity ranging from subcellular sparkles to intercellular waves is believed to be the key to a plethora of regulatory pathways in the central nervous system from synaptic plasticity to blood flow regulation. Modeling of the calcium wave initiation and transmission and their spatiotemporal dynamics is therefore an important step stone in understanding the crucial cogs of cognition. Astrocytes are active sensors of ongoing neuronal and synaptic activity, and neurotransmitters diffusing from the synaptic cleft make a strong impact on the astrocytic activity. Here we propose a model describing the patterns of calcium wave formation at a single cell level and discuss the interplay between astrocyte shape the calcium waves dynamics driven by local stochastic surges of glutamate simulating synaptic activity.

Colloid-based multiplexed method for screening plant biomass-degrading glycoside hydrolase activities in microbial communities

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

Reindl, W.; Deng, K.; Gladden, J.M.

2011-05-01

The enzymatic hydrolysis of long-chain polysaccharides is a crucial step in the conversion of biomass to lignocellulosic biofuels. The identification and characterization of optimal glycoside hydrolases is dependent on enzyme activity assays, however existing methods are limited in terms of compatibility with a broad range of reaction conditions, sample complexity, and especially multiplexity. The method we present is a multiplexed approach based on Nanostructure-Initiator Mass Spectrometry (NIMS) that allowed studying several glycolytic activities in parallel under diverse assay conditions. Although the substrate analogs carried a highly hydrophobic perfluorinated tag, assays could be performed in aqueous solutions due colloid formation ofmore » the substrate molecules. We first validated our method by analyzing known {beta}-glucosidase and {beta}-xylosidase activities in single and parallel assay setups, followed by the identification and characterization of yet unknown glycoside hydrolase activities in microbial communities.« less

DNA Recognition by a σ 54 Transcriptional Activator from Aquifex aeolicus

DOE PAGES

Vidangos, Natasha K.; Heideker, Johanna; Lyubimov, Artem; ...

2014-08-23

Transcription initiation by bacterial σ 54-polymerase requires the action of a transcriptional activator protein. Activators bind sequence-specifically upstream of the transcription initiation site via a DNA-binding domain. The structurally characterized DNA-binding domains from activators all belong to the Factor for Inversion Stimulation (Fis) family of helix-turn-helix DNA-binding proteins. We report here structures of the free and DNA-bound forms of the DNA-binding domain of NtrC4 (4DBD) from Aquifex aeolicus, a member of the NtrC family of σ 54 activators. Two NtrC4 binding sites were identified upstream (-145 and -85 base pairs) from the start of the lpxC gene, which is responsiblemore » for the first committed step in Lipid A biosynthesis. This is the first experimental evidence for σ 54 regulation in lpxC expression. 4DBD was crystallized both without DNA and in complex with the -145 binding site. The structures, together with biochemical data, indicate that NtrC4 binds to DNA in a manner that is similar to that of its close homologue, Fis. Ultimately, the greater sequence specificity for the binding of 4DBD relative to Fis seems to arise from a larger number of base specific contacts contributing to affinity than for Fis.« less

Compliance With WHO/UNICEF BFHI Standards in Croatia After Implementation of the BFHI.

PubMed

Zakarija-Grković, Irena; Boban, Marija; Janković, Sunčana; Ćuže, Anamarija; Burmaz, Tea

2018-02-01

The primary goal of the Baby-Friendly Hospital Initiative (BFHI) is to create conditions in maternity facilities that enable women to initiate and sustain the practice of breastfeeding exclusively. Research aim: This study aimed to determine hospital practices and breastfeeding rates before and after BFHI implementation and assess compliance with UNICEF/World Health Organization (WHO) standards for seven of the BFHI's Ten Steps to Successful Breastfeeding ( Ten Steps). Mothers of healthy, term infants ( N = 1,115) were recruited from the postnatal ward of the University Hospital of Split, Croatia, between February 2008 and July 2011 and followed for 12 months in a repeated-measures, prospective, longitudinal, three-group, nonequivalent, cohort study. Breastfeeding rates, hospital practices-including seven of the Ten Steps-and maternal sociodemographic data were collected. Parts of all seven Ten Steps that were assessed improved significantly post-BFHI. Step 3 ("antenatal education") showed the least improvement, whereas Step 7 ("rooming-in"; 2.6% pre-BFHI vs. 98.5% post-BFHI) and Step 9 ("no pacifiers/teats"; 21.8% pre-BFHI vs. 99.4% post-BFHI) showed the greatest improvement. Six months after Baby-Friendly designation, only Steps 7 and 9 were in full compliance with UNICEF/WHO standards. In-hospital, exclusive-breastfeeding rates rose markedly ( p < .001), but no change occurred in breastfeeding rates at 3, 6, or 12 months. Full implementation of the BFHI was associated with significant improvement in hospital practices and in-hospital, exclusive-breastfeeding rates, but it did not affect breastfeeding rates postdischarge, emphasizing the vital role of community support. Baby-Friendly Hospital Initiative standards declined rapidly post-hospital designation, indicating the need for regular monitoring and reassessment as well as ongoing, effective training for hospital staff.

Does footwear type impact the number of steps required to reach gait steady state?: an innovative look at the impact of foot orthoses on gait initiation.

PubMed

Najafi, Bijan; Miller, Daniel; Jarrett, Beth D; Wrobel, James S

2010-05-01

Many studies have attempted to better elucidate the effect of foot orthoses on gait dynamics. To our knowledge, most previous studies exclude the first few steps of gait and begin analysis at steady state walking. These unanalyzed steps of gait may contain important information about the dynamic and complex processes required to achieve equilibrium for a given gait velocity. The purpose of this study was to quantify gait initiation and determine how many steps were required to reach steady state walking under three footwear conditions: barefoot, habitual shoes, and habitual shoes with a prefabricated foot orthoses. Fifteen healthy subjects walked 50m at habitual speed in each condition. Wearing habitual shoes with the prefabricated orthoses enabled subjects to reach steady state walking in fewer steps (3.5 steps+/-2.0) compared to the barefoot condition (5.2 steps+/-3.0; p=0.02) as well as compared to the habitual shoes condition (4.7 steps+/-1.6; p=0.05). Interestingly, the subjects' dynamic medial-lateral balance was significantly improved (22%, p<0.05) by using foot orthoses compared to other footwear conditions. These findings suggest that foot orthoses may help individuals reach steady state more quickly and with a better dynamic balance in the medial-lateral direction, independent of foot type. The findings of this pilot study may open new avenues for objectively assessing the impact of prescription footwear on dynamic balance and spatio-temporal parameters of gait. Further work to better assess the impact of foot orthoses on gait initiation in patients suffering from gait and instability pathologies may be warranted. Copyright 2010 Elsevier B.V. All rights reserved.

Case Report: Activity Diagrams for Integrating Electronic Prescribing Tools into Clinical Workflow

PubMed Central

Johnson, Kevin B.; FitzHenry, Fern

2006-01-01

To facilitate the future implementation of an electronic prescribing system, this case study modeled prescription management processes in various primary care settings. The Vanderbilt e-prescribing design team conducted initial interviews with clinic managers, physicians and nurses, and then represented the sequences of steps carried out to complete prescriptions in activity diagrams. The diagrams covered outpatient prescribing for patients during a clinic visit and between clinic visits. Practice size, practice setting, and practice specialty type influenced the prescribing processes used. The model developed may be useful to others engaged in building or tailoring an e-prescribing system to meet the specific workflows of various clinic settings. PMID:16622168

An optimized fed-batch culture strategy integrated with a one-step fermentation improves L-lactic acid production by Rhizopus oryzae.

PubMed

Fu, Yongqian; Sun, Xiaolong; Zhu, Huayue; Jiang, Ru; Luo, Xi; Yin, Longfei

2018-05-21

In previous work, we proposed a novel modified one-step fermentation fed-batch strategy to efficiently generate L-lactic acid (L-LA) using Rhizopus oryzae. In this study, to further enhance efficiency of L-LA production through one-step fermentation in fed-batch cultures, we systematically investigated the initial peptone- and glucose-feeding approaches, including different initial peptone and glucose concentrations and maintained residual glucose levels. Based on the results of this study, culturing R. oryzae with initial peptone and glucose concentrations of 3.0 and 50.0 g/l, respectively, using a fed-batch strategy is an effective approach of producing L-LA through one-step fermentation. Changing the residual glucose had no obvious effect on the generation of L-LA. We determined the maximum LA production and productivity to be 162 g/l and 6.23 g/(l·h), respectively, during the acid production stage. Compared to our previous work, there was almost no change in L-LA production or yield; however, the productivity of L-LA increased by 14.3%.

Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.

PubMed

Serrao, Mariano; Ranavolo, Alberto; Conte, Carmela; Davassi, Chiara; Mari, Silvia; Fasano, Alfonso; Chini, Giorgia; Coppola, Gianluca; Draicchio, Francesco; Pierelli, Francesco

2015-11-01

The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.

Combustion efficiency determined from wall pressure and temperature measurement in a Mach 2 combustor

NASA Technical Reports Server (NTRS)

Segal, Corin; Mcdaniel, James C.; Whitehurst, Robert B.; Krauss, Roland H.

1991-01-01

A study of transverse hydrogen injection behind a rearward facing step in a Mach 2 airflow was conducted to determine the combustion efficiency and the combustor/inlet interactions at the low temperature lean-mixture operational end of a scramjet combustor model. The fuel was injected at sonic conditions into the electrically heated airstream, which was maintained at 850 K or below. The static pressure delivered at the entrance of the combustor ranged between 0.25 to 0.5 atm. Injector configurations included single and staged injectors placed at 3 or 3-and-7 step-heights downstream of the step, respectively, with injector diameters of 1, 1.5, and 2 mm. Ignition was achieved by initially unstarting the test section. The constant area combustor and the low initial temperatures caused thermal choking and upstream interaction to occur at very low equivalence ratios. Typically, most of the fuel was burned in the recirculation region behind the step and around the jets. The effects of initial conditions (temperature and pressure), fuel-to-air dynamic pressure ratio, and boundaries (thermal vs adiabatic) are presented.

Stepping responses to treadmill perturbations vary with severity of motor deficits in human SCI.

PubMed

Chu, Virginia Way Tong; Hornby, T George; Schmit, Brian D

2018-04-18

In this study, we investigated the responses to tread perturbations during human stepping on a treadmill. Our approach was to test the effects of perturbations to a single leg using a split-belt treadmill in healthy participants and in participants with varying severity of spinal cord injury (SCI). We recruited 11 people with incomplete SCI and 5 noninjured participants. As participants walked on an instrumented treadmill, the belt on one side was stopped or accelerated briefly during mid to late stance. A majority of participants initiated an unnecessary swing when the treadmill was stopped in mid stance, although the likelihood of initiating a step was decreased in participants with more severe SCI. Accelerating or decelerating one belt of the treadmill during stance altered the characteristics of swing. We observed delayed swing initiation when the belt was decelerated (i.e. the hip was in a more flexed position at time of swing) and advanced swing initiation with acceleration (i.e. hip extended at swing initiation). Further, the timing and leg posture of heel strike appeared to remain constant, reflected by a sagittal plane hip angle at heel strike that remained the same regardless of the perturbation. In summary, our results supported the current understanding of the role of sensory feedback and central drive in the control of stepping in participants with incomplete SCI and noninjured participants. In particular, the observation of unnecessary swing during a stop perturbation highlights the interdependence of central and sensory drive in walking control.

Ab initio molecular dynamics of H2O adsorbed on solid MgO

NASA Astrophysics Data System (ADS)

Langel, Walter; Parrinello, Michele

1995-08-01

The Car-Parrinello method has been applied to study the adsorption of water on solid magnesium oxide with surface defects. A step consisting of an (100) and an (010) surface on an (011) base plane allows us to model the experimentally observed microfaceting. In and on this step dissociation of water into a hydroxyl group and a H-atom took place following a complicated pathway only accessible by the simulation of thermal motion. Under comparable conditions physisorption only was observed on a regular (001) plane. This solves an experimental controversy and it is in agreement with the observation, that disordered surfaces are more active in initiating the dissociation of the water molecules. Our work allows us to identify an important active center. We can also account for the experimentally observed broadening and shifting to the red of the stretching mode of hydrogen bonded hydroxyl groups, and we provide a detailed explanation of the origin of this effect. This allows us to verify earlier theories of hydrogen bonding such as that of the adiabatic separation of the proton dynamics.

MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis.

PubMed

Bousquet, Jean; Schünemann, Holger J; Hellings, Peter W; Arnavielhe, Sylvie; Bachert, Claus; Bedbrook, Anna; Bergmann, Karl-Christian; Bosnic-Anticevich, Sinthia; Brozek, Jan; Calderon, Moises; Canonica, G Walter; Casale, Thomas B; Chavannes, Niels H; Cox, Linda; Chrystyn, Henry; Cruz, Alvaro A; Dahl, Ronald; De Carlo, Giuseppe; Demoly, Pascal; Devillier, Phillipe; Dray, Gérard; Fletcher, Monica; Fokkens, Wytske J; Fonseca, Joao; Gonzalez-Diaz, Sandra N; Grouse, Lawrence; Keil, Thomas; Kuna, Piotr; Larenas-Linnemann, Désirée; Lodrup Carlsen, Karin C; Meltzer, Eli O; Mullol, Jaoquim; Muraro, Antonella; Naclerio, Robert N; Palkonen, Susanna; Papadopoulos, Nikolaos G; Passalacqua, Giovanni; Price, David; Ryan, Dermot; Samolinski, Boleslaw; Scadding, Glenis K; Sheikh, Aziz; Spertini, François; Valiulis, Arunas; Valovirta, Erkka; Walker, Samantha; Wickman, Magnus; Yorgancioglu, Arzu; Haahtela, Tari; Zuberbier, Torsten

2016-08-01

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Treatment of simulated wastewater containing Reactive Red 195 by zero-valent iron/activated carbon combined with microwave discharge electrodeless lamp/sodium hypochlorite.

PubMed

Fu, Jie; Xu, Zhen; Li, Qing-Shan; Chen, Song; An, Shu-Qing; Zeng, Qing-Fu; Zhu, Hai-Liang

2010-01-01

A comparative study of treatment of simulated wastewater containing Reactive Red 195 using zero-valent iron/activated carbon (ZVI/AC), microwave discharge electrodeless lamp/sodium hypochlorite (MDEL/NaClO) and the combination of ZVI/AC-MDEL/NaClO was conducted. The preliminary results showed the two steps method of ZVI/AC-MDEL/NaClO had much higher degradation efficiency than both single steps. The final color removal percentage was nearly up to 100% and the chemical oxygen demand reduction percentage was up to approximately 82%. The effects of operational parameters, including initial pH value of simulated wastewater, ZVI/AC ratio and particle size of ZVI were also investigated. In addition, from the discussion of synergistic effect between ZVI/AC and MEDL/NaClO, we found that in the ZVI/AC-MEDL/NaClO process, ZVI/AC could break the azo bond firstly and then MEDL/NaClO degraded the aromatic amine products effectively. Reversing the order would reduce the degradation efficiency.

Nucleation of uniform mono- and bilayer epitaxial graphene on SiC(0001)

NASA Astrophysics Data System (ADS)

Wu, Xiaosong; Zhang, Rui; Dong, Yunliang; Guo, Shuai; Kong, Wenjie; Liao, Zhimin; Yu, Dapeng

2012-02-01

Early stage of epitaxial graphene growth on SiC(0001) has been investigated. Using the confinement controlled sublimation (CCS) method, we has achieved well controlled growth and been able to see the formation of mono- and bilayer graphene islands. The growth features reveal the intriguing growth mechanism. In particular, a new ``stepdown'' growth mode has been identified. Graphene can propagate tens of micrometers across many SiC steps, while, most importantly, step bunching is avoided and the initial regular stepped SiC surface morphology is preserved. The stepdown growth demonstrates a route towards uniform epitaxial graphene in wafer size without sacrificing the initial substrate surface morphology.

Validity of Different Activity Monitors to Count Steps in an Inpatient Rehabilitation Setting.

PubMed

Treacy, Daniel; Hassett, Leanne; Schurr, Karl; Chagpar, Sakina; Paul, Serene S; Sherrington, Catherine

2017-05-01

Commonly used activity monitors have been shown to be accurate in counting steps in active people; however, further validation is needed in slower walking populations. To determine the validity of activity monitors for measuring step counts in rehabilitation inpatients compared with visually observed step counts. To explore the influence of gait parameters, activity monitor position, and use of walkers on activity monitor accuracy. One hundred and sixty-six inpatients admitted to a rehabilitation unit with an average walking speed of 0.4 m/s (SD 0.2) wore 16 activity monitors (7 different devices in different positions) simultaneously during 6-minute and 6-m walks. The number of steps taken during the tests was also counted by a physical therapist. Gait parameters were assessed using the GAITRite system. To analyze the influence of different gait parameters, the percentage accuracy for each monitor was graphed against various gait parameters for each activity monitor. The StepWatch, Fitbit One worn on the ankle and the ActivPAL showed excellent agreement with observed step count (ICC 2,1 0.98; 0.92; 0.78 respectively). Other devices (Fitbit Charge, Fitbit One worn on hip, G-Sensor, Garmin Vivofit, Actigraph) showed poor agreement with the observed step count (ICC 2,1 0.12-0.40). Percentage agreement with observed step count was highest for the StepWatch (mean 98%). The StepWatch and the Fitbit One worn on the ankle maintained accuracy in individuals who walked more slowly and with shorter strides but other devices were less accurate in these individuals. There were small numbers of participants for some gait parameters. The StepWatch showed the highest accuracy and closest agreement with observed step count. This device can be confidently used by researchers for accurate measurement of step counts in inpatient rehabilitation in individuals who walk slowly. If immediate feedback is desired, the Fitbit One when worn on the ankle would be the best choice for this population. © 2017 American Physical Therapy Association

The Influence of the Local Neighbourhood Environment on Walking Levels during the Walking for Wellbeing in the West Pedometer-Based Community Intervention

PubMed Central

Robertson, L. B.; Ward Thompson, C.; Aspinall, P.; Millington, C.; McAdam, C.; Mutrie, N.

2012-01-01

We investigated the relationship between walking levels and the local neighbourhood physical environment during the Walking for Wellbeing in the West (WWW) randomised pedometer-based community intervention. Walking activity was recorded as step counts at baseline (n = 76), and at 3 months (n = 57), 6 months (n = 54), and 12 months (n = 45) post-intervention. Objective physical environment data were obtained from GIS datasets and street surveys conducted using the SWAT audit tool. Sixty-nine environment variables were reduced to eight environment factors using principal axis factoring, and the relationship between environment factors and (i) step counts, and (ii) the change in step counts relative to baseline, was examined using hierarchical multiple linear regression, controlling for age, gender, income, and deprivation. Five environment factors were significant predictors of step counts, but none were significant predictors of the change in step counts relative to baseline. None of the demographic variables included in the analysis were significant predictors at any stage of the study. Total variance explained by the environment ranged from 6% (P < 0.05) to 34% (P < 0.01), with lowest levels during the initial stages of the study. The physical environment appears to have influenced walking levels during the WWW intervention, and to have contributed to the maintenance of walking levels post-intervention. PMID:22899944

The influence of the local neighbourhood environment on walking levels during the Walking for Wellbeing in the West pedometer-based community intervention.

PubMed

Robertson, L B; Ward Thompson, C; Aspinall, P; Millington, C; McAdam, C; Mutrie, N

2012-01-01

We investigated the relationship between walking levels and the local neighbourhood physical environment during the Walking for Wellbeing in the West (WWW) randomised pedometer-based community intervention. Walking activity was recorded as step counts at baseline (n = 76), and at 3 months (n = 57), 6 months (n = 54), and 12 months (n = 45) post-intervention. Objective physical environment data were obtained from GIS datasets and street surveys conducted using the SWAT audit tool. Sixty-nine environment variables were reduced to eight environment factors using principal axis factoring, and the relationship between environment factors and (i) step counts, and (ii) the change in step counts relative to baseline, was examined using hierarchical multiple linear regression, controlling for age, gender, income, and deprivation. Five environment factors were significant predictors of step counts, but none were significant predictors of the change in step counts relative to baseline. None of the demographic variables included in the analysis were significant predictors at any stage of the study. Total variance explained by the environment ranged from 6% (P < 0.05) to 34% (P < 0.01), with lowest levels during the initial stages of the study. The physical environment appears to have influenced walking levels during the WWW intervention, and to have contributed to the maintenance of walking levels post-intervention.

How many steps/day are enough? For adults.

PubMed

Tudor-Locke, Catrine; Craig, Cora L; Brown, Wendy J; Clemes, Stacy A; De Cocker, Katrien; Giles-Corti, Billie; Hatano, Yoshiro; Inoue, Shigeru; Matsudo, Sandra M; Mutrie, Nanette; Oppert, Jean-Michel; Rowe, David A; Schmidt, Michael D; Schofield, Grant M; Spence, John C; Teixeira, Pedro J; Tully, Mark A; Blair, Steven N

2011-07-28

Physical activity guidelines from around the world are typically expressed in terms of frequency, duration, and intensity parameters. Objective monitoring using pedometers and accelerometers offers a new opportunity to measure and communicate physical activity in terms of steps/day. Various step-based versions or translations of physical activity guidelines are emerging, reflecting public interest in such guidance. However, there appears to be a wide discrepancy in the exact values that are being communicated. It makes sense that step-based recommendations should be harmonious with existing evidence-based public health guidelines that recognize that "some physical activity is better than none" while maintaining a focus on time spent in moderate-to-vigorous physical activity (MVPA). Thus, the purpose of this review was to update our existing knowledge of "How many steps/day are enough?", and to inform step-based recommendations consistent with current physical activity guidelines. Normative data indicate that healthy adults typically take between 4,000 and 18,000 steps/day, and that 10,000 steps/day is reasonable for this population, although there are notable "low active populations." Interventions demonstrate incremental increases on the order of 2,000-2,500 steps/day. The results of seven different controlled studies demonstrate that there is a strong relationship between cadence and intensity. Further, despite some inter-individual variation, 100 steps/minute represents a reasonable floor value indicative of moderate intensity walking. Multiplying this cadence by 30 minutes (i.e., typical of a daily recommendation) produces a minimum of 3,000 steps that is best used as a heuristic (i.e., guiding) value, but these steps must be taken over and above habitual activity levels to be a true expression of free-living steps/day that also includes recommendations for minimal amounts of time in MVPA. Computed steps/day translations of time in MVPA that also include estimates of habitual activity levels equate to 7,100 to 11,000 steps/day. A direct estimate of minimal amounts of MVPA accumulated in the course of objectively monitored free-living behaviour is 7,000-8,000 steps/day. A scale that spans a wide range of incremental increases in steps/day and is congruent with public health recognition that "some physical activity is better than none," yet still incorporates step-based translations of recommended amounts of time in MVPA may be useful in research and practice. The full range of users (researchers to practitioners to the general public) of objective monitoring instruments that provide step-based outputs require good reference data and evidence-based recommendations to be able to design effective health messages congruent with public health physical activity guidelines, guide behaviour change, and ultimately measure, track, and interpret steps/day.

How many steps/day are enough? for adults

PubMed Central

2011-01-01

Physical activity guidelines from around the world are typically expressed in terms of frequency, duration, and intensity parameters. Objective monitoring using pedometers and accelerometers offers a new opportunity to measure and communicate physical activity in terms of steps/day. Various step-based versions or translations of physical activity guidelines are emerging, reflecting public interest in such guidance. However, there appears to be a wide discrepancy in the exact values that are being communicated. It makes sense that step-based recommendations should be harmonious with existing evidence-based public health guidelines that recognize that "some physical activity is better than none" while maintaining a focus on time spent in moderate-to-vigorous physical activity (MVPA). Thus, the purpose of this review was to update our existing knowledge of "How many steps/day are enough?", and to inform step-based recommendations consistent with current physical activity guidelines. Normative data indicate that healthy adults typically take between 4,000 and 18,000 steps/day, and that 10,000 steps/day is reasonable for this population, although there are notable "low active populations." Interventions demonstrate incremental increases on the order of 2,000-2,500 steps/day. The results of seven different controlled studies demonstrate that there is a strong relationship between cadence and intensity. Further, despite some inter-individual variation, 100 steps/minute represents a reasonable floor value indicative of moderate intensity walking. Multiplying this cadence by 30 minutes (i.e., typical of a daily recommendation) produces a minimum of 3,000 steps that is best used as a heuristic (i.e., guiding) value, but these steps must be taken over and above habitual activity levels to be a true expression of free-living steps/day that also includes recommendations for minimal amounts of time in MVPA. Computed steps/day translations of time in MVPA that also include estimates of habitual activity levels equate to 7,100 to 11,000 steps/day. A direct estimate of minimal amounts of MVPA accumulated in the course of objectively monitored free-living behaviour is 7,000-8,000 steps/day. A scale that spans a wide range of incremental increases in steps/day and is congruent with public health recognition that "some physical activity is better than none," yet still incorporates step-based translations of recommended amounts of time in MVPA may be useful in research and practice. The full range of users (researchers to practitioners to the general public) of objective monitoring instruments that provide step-based outputs require good reference data and evidence-based recommendations to be able to design effective health messages congruent with public health physical activity guidelines, guide behaviour change, and ultimately measure, track, and interpret steps/day. PMID:21798015

MO-D-213-01: Workflow Monitoring for a High Volume Radiation Oncology Center

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

Laub, S; Dunn, M; Galbreath, G

2015-06-15

Purpose: Implement a center wide communication system that increases interdepartmental transparency and accountability while decreasing redundant work and treatment delays by actively monitoring treatment planning workflow. Methods: Intake Management System (IMS), a program developed by ProCure Treatment Centers Inc., is a multi-function database that stores treatment planning process information. It was devised to work with the oncology information system (Mosaiq) to streamline interdepartmental workflow.Each step in the treatment planning process is visually represented and timelines for completion of individual tasks are established within the software. The currently active step of each patient’s planning process is highlighted either red or greenmore » according to whether the initially allocated amount of time has passed for the given process. This information is displayed as a Treatment Planning Process Monitor (TPPM), which is shown on screens in the relevant departments throughout the center. This display also includes the individuals who are responsible for each task.IMS is driven by Mosaiq’s quality checklist (QCL) functionality. Each step in the workflow is initiated by a Mosaiq user sending the responsible party a QCL assignment. IMS is connected to Mosaiq and the sending or completing of a QCL updates the associated field in the TPPM to the appropriate status. Results: Approximately one patient a week is identified during the workflow process as needing to have his/her treatment start date modified or resources re-allocated to address the most urgent cases. Being able to identify a realistic timeline for planning each patient and having multiple departments communicate their limitations and time constraints allows for quality plans to be developed and implemented without overburdening any one department. Conclusion: Monitoring the progression of the treatment planning process has increased transparency between departments, which enables efficient communication. Having built-in timelines allows easy prioritization of tasks and resources and facilitates effective time management.« less

Structure of the beta-galactosidase gene from Thermus sp. strain T2: expression in Escherichia coli and purification in a single step of an active fusion protein.

PubMed

Vian, A; Carrascosa, A V; García, J L; Cortés, E

1998-06-01

The nucleotide sequence of both the bgaA gene, coding for a thermostable beta-galactosidase of Thermus sp. strain T2, and its flanking regions was determined. The deduced amino acid sequence of the enzyme predicts a polypeptide of 645 amino acids (Mr, 73,595). Comparative analysis of the open reading frames located in the flanking regions of the bgaA gene revealed that they might encode proteins involved in the transport and hydrolysis of sugars. The observed homology between the deduced amino acid sequences of BgaA and the beta-galactosidase of Bacillus stearothermophilus allows us to classify the new enzyme within family 42 of glycosyl hydrolases. BgaA was overexpressed in its active form in Escherichia coli, but more interestingly, an active chimeric beta-galactosidase was constructed by fusing the BgaA protein to the choline-binding domain of the major pneumococcal autolysin. This chimera illustrates a novel approach for producing an active and thermostable hybrid enzyme that can be purified in a single step by affinity chromatography on DEAE-cellulose, retaining the catalytic properties of the native enzyme. The chimeric enzyme showed a specific activity of 191,000 U/mg at 70 degrees C and a Km value of 1.6 mM with o-nitrophenyl-beta-D-galactopyranoside as a substrate, and it retained 50% of its initial activity after 1 h of incubation at 70 degrees C.

Response of ryanodine receptor channels to Ca2+ steps produced by rapid solution exchange.

PubMed Central

Laver, D R; Curtis, B A

1996-01-01

We used a flow method for Ca2+ activation of sheep cardiac and rabbit skeletal ryanodine receptor (RyR) channels in lipid bilayers, which activated RyRs in < 20 ms and maintained a steady [Ca2+] for 5 s. [Ca2+] was rapidly altered by flowing Ca(2+)-buffered solutions containing 100 or 200 microM Ca2+ from a perfusion tube inserted in the cis, myoplasmic chamber above the bilayer. During steps from 0.1 to 100 microM, [Ca2+] reached 0.3 microM (activation threshold) and 10 microM (maximum Po) in times consistent with predictions of a solution exchange model. Immediately following rapid RyR activation, Po was 0.67 (cardiac) and 0.45 (skeletal) at a holding voltage of +40 mV (cis/trans). Po then declined (at constant [Ca2+]) in 70% of channels (n = 25) with time constants ranging from .5 to 15 s. The mechanism for Po decline, whether it be adaptation or inactivation, was not determined in this study. cis, 2 mM Mg2+ reduced the initial Po for skeletal RyRs to 0.21 and marginally slowed the declining phase. During very rapid falls in [Ca2+] from mM (inhibited) to sub-microM (sub-activating) levels, skeletal RyR did not open. We conclude the RyR gates responsible for Ca(2+)-dependent activation and inhibition of skeletal RyRs can gate independently. Images FIGURE 1 FIGURE 8 PMID:8842211

Sustainability of the whole-community project '10,000 Steps': a longitudinal study.

PubMed

Van Acker, Ragnar; De Bourdeaudhuij, Ilse; De Cocker, Katrien; Klesges, Lisa M; Willem, Annick; Cardon, Greet

2012-03-05

In the dissemination and implementation literature, there is a dearth of information on the sustainability of community-wide physical activity (PA) programs in general and of the '10,000 Steps' project in particular. This paper reports a longitudinal evaluation of organizational and individual sustainability indicators of '10,000 Steps'. Among project adopters, department heads of 24 public services were surveyed 1.5 years after initially reported project implementation to assess continuation, institutionalization, sustained implementation of intervention components, and adaptations. Barriers and facilitators of project sustainability were explored. Citizens (n = 483) living near the adopting organizations were interviewed to measure maintenance of PA differences between citizens aware and unaware of '10,000 Steps'. Independent-samples t, Mann-Whitney U, and chi-square tests were used to compare organizations for representativeness and individual PA differences. Of all organizations, 50% continued '10,000 Steps' (mostly in cycles) and continuation was independent of organizational characteristics. Level of intervention institutionalization was low to moderate on evaluations of routinization and moderate for project saturation. The global implementation score (58%) remained stable and three of nine project components were continued by less than half of organizations (posters, street signs and variants, personalized contact). Considerable independent adaptations of the project were reported (e.g. campaign image). Citizens aware of '10,000 Steps' remained more active during leisure time than those unaware (227 ± 235 and 176 ± 198 min/week, respectively; t = -2.6; p < .05), and reported more household-related (464 ± 397 and 389 ± 346 min/week, respectively; t = -2.2; p < .05) and moderate-intensity-PA (664 ± 424 and 586 ± 408 min/week, respectively; t = -2.0; p < .05). Facilitators of project sustainability included an organizational leader supporting the project, availability of funding or external support, and ready-for-use materials with ample room for adaptation. Barriers included insufficient synchronization between regional and community policy levels and preference for other PA projects. '10,000 Steps' could remain sustainable but design, organizational, and contextual barriers need consideration. Sustainability of '10,000 Steps' in organizations can occur in cycles rather than in ongoing projects. Future research should compare sustainability other whole-community PA projects with '10,000 Steps' to contrast sustainability of alternative models of whole-community PA projects. This would allow optimization of project elements and methods to support decisions of choice for practitioners.

Three-Dimensional Structure of Boundary Layers in Transition to Turbulence

DTIC Science & Technology

1989-03-01

step-by-step Orr- Sommerfeld solution and integration. What is needed is an initial condition and initial wavenumber. These data can be obtained from a ...general than unsteady boundary-layer equations and Orr- Sommerfeld equation which are special cases. There- fore, the PSE will be a valuable tool for...spectra (discrete, continuous) result in a given problem is discussed in monographs and journal articles. Here, we try to find solutions to the

Electrochemical and Structural Study of a Chemically Dealloyed PtCu Oxygen Reduction Catalyst

PubMed Central

Dutta, Indrajit; Carpenter, Michael K; Balogh, Michael P; Ziegelbauer, Joseph M; Moylan, Thomas E; Atwan, Mohammed H; Irish, Nicholas P

2013-01-01

A carbon-supported, dealloyed platinum-copper (Pt-Cu) oxygen reduction catalyst was prepared using a multi-step synthetic procedure. Material produced at each step was characterized using high angle annular dark field scanning transmission electron microscopy (HAADF-STEM), electron energy loss spectroscopy (EELS) mapping, x-ray absorption spectroscopy (XAS), x-ray diffraction (XRD), and cyclic voltammetry (CV), and its oxygen reduction reaction (ORR) activity was measured by a thin-film rotating disk electrode (TF-RDE) technique. The initial synthetic step, a co-reduction of metal salts, produced a range of poorly crystalline Pt, Cu, and Pt-Cu alloy nanoparticles that nevertheless exhibited good ORR activity. Annealing this material alloyed the metals and increased particle size and crystallinity. TEM shows the annealed catalyst to include particles of various sizes, large (>25 nm), medium (12–25 nm), and small (<12 nm). Most of the small and medium-sized particles exhibited a partial or complete coreshell (Cu-rich core and Pt shell) structure with the smaller particles typically having more complete shells. The appearance of Pt shells after annealing indicates that they are formed by a thermal diffusion mechanism. Although the specific activity of the catalyst material was more than doubled by annealing, the concomitant decrease in Pt surface area resulted in a drop in its mass activity. Subsequent dealloying of the catalyst by acid treatment to partially remove the copper increased the Pt surface area by changing the morphology of the large and some medium particles to a “Swiss cheese” type structure having many voids. The smaller particles retained their core-shell structure. The specific activity of the catalyst material was little reduced by dealloying, but its mass activity was more than doubled due to the increase in surface area. The possible origins of these results are discussed in this report. PMID:23807900

Subsurface oxide plays a critical role in CO 2 activation by Cu(111) surfaces to form chemisorbed CO 2, the first step in reduction of CO 2

DOE PAGES

Favaro, Marco; Xiao, Hai; Cheng, Tao; ...

2017-06-12

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide ismore » essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.« less

Billing third party payers for pharmaceutical care services.

PubMed

Poirier, S; Buffington, D E; Memoli, G A

1999-01-01

To describe the steps pharmacists must complete when seeking compensation from third party payers for pharmaceutical care services. Government publications; professional publications, including manuals and newsletters; authors' personal experience. Pharmacists in increasing numbers are meeting with success in getting reimbursed by third party payers for patient care activities. However, many pharmacists remain reluctant to seek compensation because they do not understand the steps involved. Preparatory steps include obtaining a provider/supplier number, procuring appropriate claim forms, developing data collection and documentation systems, establishing professional fees, creating a marketing plan, and developing an accounting system. To bill for specific patient care services, pharmacists need to collect the patient's insurance information, obtain a statement of medical necessity from the patient's physician, complete the appropriate claim form accurately, and submit the claim with supporting documentation to the insurer. Although many claims from pharmacists are rejected initially, pharmacists who work with third party payers to understand the reasons for denial of payment often receive compensation when claims are resubmitted. Pharmacists who follow these guidelines for billing third party payers for pharmaceutical care services should notice an increase in the number of paid claims.

A DFT Investigation of the Mechanism of Propene Ammoxidation over α-Bismuth Molybdate

DOE PAGES

Licht, Rachel B.; Bell, Alexis T.

2016-11-17

We investigated the mechanisms and energetics for the propene oxidation and ammoxidation occurring on the (010) surface of Bi 2 Mo 3 O 12 using density functional theory (DFT). An energetically feasible sequence of elementary steps for propene oxidation to acrolein, propene ammoxidation to acrylonitrile, and acrolein ammoxidation to acrylonitrile is proposed. Consistent with experimental findings, the rate-limiting step for both propene oxidation and ammoxidation is the initial hydrogen abstraction from the methyl group of propene, which is calculated to have an apparent activation energy of 27.3 kcal/mol. The allyl species produced in this reaction is stabilized as an allylmore » alkoxide, which can then undergo hydrogen abstraction to form acrolein or react with ammonia adsorbed on under-coordinated surface Bi 3+ cations to form allylamine. Dehydrogenation of allylamine is shown to produce acrylonitrile, whereas reaction with additional adsorbed ammonia leads to the formation of acetonitrile and hydrogen cyanide. The dehydrogenation of allyalkoxide species is found to have a significantly higher activation barrier than reaction with adsorbed ammonia, consistent with the observation that very little acrolein is produced when ammonia is present. Finally, we found that rapid reoxidation of the catalyst surface to release wate the driving force for all reactions involving the cleavage of C-H or N-H bonds, because practically all of these steps are endothermic. (Chemical Equation Presented).« less

A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157.

PubMed

Preugschat, Frank; Carter, Luke H; Boros, Eric E; Porter, David J T; Stewart, Eugene L; Shewchuk, Lisa M

2014-12-15

hCD157 catalyzes the hydrolysis of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The release of nicotinamide or nicotinic acid from NR or NAR was confirmed by spectrophotometric, HPLC and NMR analyses. hCD157 is inactivated by a mechanism-based inhibitor, 2'-deoxy-2'-fluoro-nicotinamide arabinoside (fNR). Modification of the enzyme during the catalytic cycle by NR, NAR, or fNR increased the intrinsic protein fluorescence by approximately 50%. Pre-steady state and steady state data were used to derive a minimal kinetic scheme for the hydrolysis of NR. After initial complex formation a reversible step (360 and 30s(-1)) is followed by a slow irreversible step (0.1s(-1)) that defined the rate limiting step, or kcat. The calculated KMapp value for NR in the hydrolytic reaction is 6nM. The values of the kinetic constants suggest that one biological function of cell-surface hCD157 is to bind and slowly hydrolyze NR, possibly converting it to a ligand-activated receptor. Differences in substrate preference between hCD157 and hCD38 were rationalized through a comparison of the crystal structures of the two proteins. This comparison identified several residues in hCD157 (F108 and F173) that can potentially hinder the binding of dinucleotide substrates (NAD+). Copyright © 2014 Elsevier Inc. All rights reserved.

Multilevel Evaluation Alignment: An Explication of a Four-Step Model

ERIC Educational Resources Information Center

Yang, Huilan; Shen, Jianping; Cao, Honggao; Warfield, Charles

2004-01-01

Using the evaluation work on the W.K. Kellogg Foundation's Unleashing Resources Initiative as an example, in this article we explicate a general four-step model appropriate for multilevel evaluation alignment. We review the relevant literature, argue for the need for evaluation alignment in a multilevel context, explain the four-step model,…

Suppression of the Escherichia coli dnaA46 mutation by changes in the activities of the pyruvate-acetate node links DNA replication regulation to central carbon metabolism.

PubMed

Tymecka-Mulik, Joanna; Boss, Lidia; Maciąg-Dorszyńska, Monika; Matias Rodrigues, João F; Gaffke, Lidia; Wosinski, Anna; Cech, Grzegorz M; Szalewska-Pałasz, Agnieszka; Węgrzyn, Grzegorz; Glinkowska, Monika

2017-01-01

To ensure faithful transmission of genetic material to progeny cells, DNA replication is tightly regulated, mainly at the initiation step. Escherichia coli cells regulate the frequency of initiation according to growth conditions. Results of the classical, as well as the latest studies, suggest that the DNA replication in E. coli starts at a predefined, constant cell volume per chromosome but the mechanisms coordinating DNA replication with cell growth are still not fully understood. Results of recent investigations have revealed a role of metabolic pathway proteins in the control of cell division and a direct link between metabolism and DNA replication has also been suggested both in Bacillus subtilis and E. coli cells. In this work we show that defects in the acetate overflow pathway suppress the temperature-sensitivity of a defective replication initiator-DnaA under acetogenic growth conditions. Transcriptomic and metabolic analyses imply that this suppression is correlated with pyruvate accumulation, resulting from alterations in the pyruvate dehydrogenase (PDH) activity. Consequently, deletion of genes encoding the pyruvate dehydrogenase subunits likewise resulted in suppression of the thermal-sensitive growth of the dnaA46 strain. We propose that the suppressor effect may be directly related to the PDH complex activity, providing a link between an enzyme of the central carbon metabolism and DNA replication.

[Inflammatory process in atherogenesis: new facts about old flame].

PubMed

Vucević, Danijela; Radak, Dorde; Radosavljević, Tatjana; Mladenović, Dusan; Milovanović, Ivan

2012-01-01

INTRODUCTION. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of this disease is not fully understood. Endothelial Dysfunction and Inflammatory Process. Endothelial dysfunction is recognized as the crucial step in atherogenesis. A lot of studies have confirmed the involvement of various mediators of inflammation in initial proatherogenic processes, such as the upregulation of adhesion molecules on endothelial cells, binding of low density lipoproteins to endothelium, activation of macrophages and proliferation of vascular smooth muscle cells. Fatty stain and Inflammatory Process. Fatty stain consists of foam cell accumulation. After foam cell formation, mediators of inflammation initiate a series ofintracellular events that include the induction of inflammatory cytokines. Thus, a vicious circle of inflammation, modification of lipoproteins and further inflammation can be maintained in the artery. Transitory Lesion and Inflammatory Process. In transitory lesion intensive phagocytosis of oxidized low density lipoproteins additionally activates monocytes and macrophages and consequently facilitates and exacerbates the inflammatory response. Fibrotic Plaque and Inflammatory Process. Inflammatory process, matrix-degrading metalloproteinases activity, platelets aggregation and smooth muscle cells proliferation play a central role in development of fibrotic plaque. Complex Lesion and Inflammatory Process. It has been shown that inflammation is closely related to the development of atherosclerotic plaque rupture. The contribution of inflammatory process has become increasingly meaningful in understanding the initiation, progression and clinical manifestations ofatherosclerosis.

A TBP-containing multiprotein complex (TIF-IB) mediates transcription specificity of murine RNA polymerase I.

PubMed

Eberhard, D; Tora, L; Egly, J M; Grummt, I

1993-09-11

TIF-IB is a transcription factor which interacts with the mouse ribosomal gene promoter and nucleates the formation of an initiation complex containing RNA polymerase I (Pol I). We have purified this factor to near homogeneity and demonstrate that TIF-IB is a large complex (< 200 kDa) which contains several polypeptides. One of the subunits present in this protein complex is the TATA-binding protein (TBP) as revealed by copurification of TIF-IB activity and TBP over different chromatographic steps including immunoaffinity purification. In addition to TBP, three tightly associated proteins (TAFs-I) with apparent molecular weights of 95, 68, and 48 kDa are contained in this multimeric complex. This subunit composition is similar--but not identical--to the analogous human factor SL1. Depletion of TBP from TIF-IB-containing fractions by immunoprecipitation eliminates TIF-IB activity. Neither TBP alone nor fractions containing other TBP complexes are capable of substituting for TIF-IB activity. Therefore, TIF-IB is a unique complex with Pol I-specific TAFs distinct from other TBP-containing complexes. The identification of TBP as an integral part of the murine rDNA promoter-specific transcription initiation factor extends the previously noted similarity of transcriptional initiation by the three nuclear RNA polymerases and underscores the importance of TAFs in determining promoter specificity.

A TBP-containing multiprotein complex (TIF-IB) mediates transcription specificity of murine RNA polymerase I.

PubMed Central

Eberhard, D; Tora, L; Egly, J M; Grummt, I

1993-01-01

TIF-IB is a transcription factor which interacts with the mouse ribosomal gene promoter and nucleates the formation of an initiation complex containing RNA polymerase I (Pol I). We have purified this factor to near homogeneity and demonstrate that TIF-IB is a large complex (< 200 kDa) which contains several polypeptides. One of the subunits present in this protein complex is the TATA-binding protein (TBP) as revealed by copurification of TIF-IB activity and TBP over different chromatographic steps including immunoaffinity purification. In addition to TBP, three tightly associated proteins (TAFs-I) with apparent molecular weights of 95, 68, and 48 kDa are contained in this multimeric complex. This subunit composition is similar--but not identical--to the analogous human factor SL1. Depletion of TBP from TIF-IB-containing fractions by immunoprecipitation eliminates TIF-IB activity. Neither TBP alone nor fractions containing other TBP complexes are capable of substituting for TIF-IB activity. Therefore, TIF-IB is a unique complex with Pol I-specific TAFs distinct from other TBP-containing complexes. The identification of TBP as an integral part of the murine rDNA promoter-specific transcription initiation factor extends the previously noted similarity of transcriptional initiation by the three nuclear RNA polymerases and underscores the importance of TAFs in determining promoter specificity. Images PMID:8414971

Isolation and functional characterization of TIF-IB, a factor that confers promoter specificity to mouse RNA polymerase I.

PubMed

Schnapp, A; Clos, J; Hädelt, W; Schreck, R; Cvekl, A; Grummt, I

1990-03-25

The murine ribosomal gene promoter contains two cis-acting control elements which operate in concert to promote efficient and accurate transcription initiation by RNA polymerase I. The start site proximal core element which is indispensable for promoter recognition by RNA polymerase I (pol I) encompasses sequences from position -39 to -1. An upstream control element (UCE) which is located between nucleotides -142 and -112 stimulates the efficiency of transcription initiation both in vivo and in vitro. Here we report the isolation and functional characterization of a specific rDNA binding protein, the transcription initiation factor TIF-IB, which specifically interacts with the core region of the mouse ribosomal RNA gene promoter. Highly purified TIF-IB complements transcriptional activity in the presence of two other essential initiation factors TIF-IA and TIF-IC. We demonstrate that the binding efficiency of purified TIF-IB to the core promoter is strongly enhanced by the presence in cis of the UCE. This positive effect of upstream sequences on TIF-IB binding is observed throughout the purification procedure suggesting that the synergistic action of the two distant promoter elements is not mediated by a protein different from TIF-IB. Increasing the distance between both control elements still facilitates stable factor binding but eliminates transcriptional activation. The results demonstrate that TIF-IB binding to the rDNA promoter is an essential early step in the assembly of a functional transcription initiation complex. The subsequent interaction of TIF-IB with other auxiliary transcription initiation factors, however, requires the correct spacing between the UCE and the core promoter element.

Hyperthermophilic Archaeon Thermococcus kodakarensis Utilizes a Four-Step Pathway for NAD+ Salvage through Nicotinamide Deamination.

PubMed

Hachisuka, Shin-Ichi; Sato, Takaaki; Atomi, Haruyuki

2018-06-01

Many organisms possess pathways that regenerate NAD + from its degradation products, and two pathways are known to salvage NAD + from nicotinamide (Nm). One is a four-step pathway that proceeds through deamination of Nm to nicotinic acid (Na) by Nm deamidase and phosphoribosylation to nicotinic acid mononucleotide (NaMN), followed by adenylylation and amidation. Another is a two-step pathway that does not involve deamination and directly proceeds with the phosphoribosylation of Nm to nicotinamide mononucleotide (NMN), followed by adenylylation. Judging from genome sequence data, the hyperthermophilic archaeon Thermococcus kodakarensis is supposed to utilize the four-step pathway, but the fact that the adenylyltransferase encoded by TK0067 recognizes both NMN and NaMN also raises the possibility of a two-step salvage mechanism. Here, we examined the substrate specificity of the recombinant TK1676 protein, annotated as nicotinic acid phosphoribosyltransferase. The TK1676 protein displayed significant activity toward Na and phosphoribosyl pyrophosphate (PRPP) and only trace activity with Nm and PRPP. We further performed genetic analyses on TK0218 (quinolinic acid phosphoribosyltransferase) and TK1650 (Nm deamidase), involved in de novo biosynthesis and four-step salvage of NAD + , respectively. The ΔTK0218 mutant cells displayed growth defects in a minimal synthetic medium, but growth was fully restored with the addition of Na or Nm. The ΔTK0218 ΔTK1650 mutant cells did not display growth in the minimal medium, and growth was restored with the addition of Na but not Nm. The enzymatic and genetic analyses strongly suggest that NAD + salvage in T. kodakarensis requires deamination of Nm and proceeds through the four-step pathway. IMPORTANCE Hyperthermophiles must constantly deal with increased degradation rates of their biomolecules due to their high growth temperatures. Here, we identified the pathway that regenerates NAD + from nicotinamide (Nm) in the hyperthermophilic archaeon Thermococcus kodakarensis The organism utilizes a four-step pathway that initially hydrolyzes the amide bond of Nm to generate nicotinic acid (Na), followed by phosphoribosylation, adenylylation, and amidation. Although the two-step pathway, consisting of only phosphoribosylation of Nm and adenylylation, seems to be more efficient, Nm mononucleotide in the two-step pathway is much more thermolabile than Na mononucleotide, the corresponding intermediate in the four-step pathway. Although NAD + itself is thermolabile, this may represent an example of a metabolism that has evolved to avoid the use of thermolabile intermediates. Copyright © 2018 American Society for Microbiology.

Validity of Activity Monitor Step Detection Is Related to Movement Patterns.

PubMed

Hickey, Amanda; John, Dinesh; Sasaki, Jeffer E; Mavilia, Marianna; Freedson, Patty

2016-02-01

There is a need to examine step-counting accuracy of activity monitors during different types of movements. The purpose of this study was to compare activity monitor and manually counted steps during treadmill and simulated free-living activities and to compare the activity monitor steps to the StepWatch (SW) in a natural setting. Fifteen participants performed laboratory-based treadmill (2.4, 4.8, 7.2 and 9.7 km/h) and simulated free-living activities (eg, cleaning room) while wearing an activPAL, Omron HJ720-ITC, Yamax Digi- Walker SW-200, 2 ActiGraph GT3Xs (1 in "low-frequency extension" [AGLFE] and 1 in "normal-frequency" mode), an ActiGraph 7164, and a SW. Participants also wore monitors for 1-day in their free-living environment. Linear mixed models identified differences between activity monitor steps and the criterion in the laboratory/free-living settings. Most monitors performed poorly during treadmill walking at 2.4 km/h. Cleaning a room had the largest errors of all simulated free-living activities. The accuracy was highest for forward/rhythmic movements for all monitors. In the free-living environment, the AGLFE had the largest discrepancy with the SW. This study highlights the need to verify step-counting accuracy of activity monitors with activities that include different movement types/directions. This is important to understand the origin of errors in step-counting during free-living conditions.

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease.

PubMed

Nakamura, Yu; Strohmaier, Christine; Tamura, Kaoru; Kataoka, Naoko; Nakano, Masayuki; Oda, Shoichiro; Nishimura, Kazuma; Homma, Akira

2015-01-01

To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm(2) and titrated to 10 cm(2) after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm(2) and titrated by 2.5 cm(2) every 4 weeks to 10 cm(2)). A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was -3.6% (95% confidence interval: -17.0, 9.6), falling within the prespecified acceptance range. The tolerability of two different titration schemes was similar in Japanese patients with AD.

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

PubMed Central

Nakamura, Yu; Strohmaier, Christine; Tamura, Kaoru; Kataoka, Naoko; Nakano, Masayuki; Oda, Shoichiro; Nishimura, Kazuma; Homma, Akira

2015-01-01

Aim To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm2 and titrated to 10 cm2 after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm2 and titrated by 2.5 cm2 every 4 weeks to 10 cm2). Methods A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Results Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6), falling within the prespecified acceptance range. Conclusion The tolerability of two different titration schemes was similar in Japanese patients with AD. PMID:26557135

Measured close lightning leader-step electric-field-derivative waveforms.

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

Jordan, Doug M.; Hill, Dustin; Biagi, Christopher J.

2010-12-01

We characterize the measured electric field-derivative (dE/dt) waveforms of lightning stepped-leader steps from three negative lightning flashes at distances of tens to hundreds of meters. Electromagnetic signatures of leader steps at such close distances have rarely been documented in previous literature. Individual leader-step three-dimensional locations are determined by a dE/dt TOA system. The leader-step field derivative is typically a bipolar pulse with a sharp initial half-cycle of the same polarity as that of the return stroke, followed by an opposite polarity overshoot that decays relatively slowly to background level. This overshoot increases in amplitude relative to the initial peak andmore » becomes dominant as range decreases. The initial peak is often preceded by a 'slow front,' similar to the slow front that precedes the fast transition to peak in first return stroke dE/dt and E waveforms. The overall step-field waveform duration is typically less than 1 {micro}s. The mean initial peak of dE/dt, range-normalized to 100 km, is 7.4 V m{sup -1} {micro}s{sup -1} (standard deviation (S.D.), 3.7 V m{sup -1} {micro}s{sup -1}, N = 103), the mean half-peak width is 33.5 ns (S.D., 11.9 ns, N = 69), and the mean 10-to-90% risetime is 43.6 ns (S.D., 24.2 ns, N = 69). From modeling, we determine the properties of the leader step currents which produced two typical measured field derivatives, and we use one of these currents to calculate predicted leader step E and dE/dt as a function of source range and height, the results being in good agreement with our observations. The two modeled current waveforms had maximum rates of current rise-to-peak near 100 kA {micro}s{sup -1}, peak currents in the 5-7 kA range, current half-peak widths of about 300 ns, and charge transfers of {approx}3 mC. As part of the modeling, those currents were propagated upward at 1.5 x 10{sup 8} m s{sup -1}, with their amplitudes decaying exponentially with a decay height constant of 25 m.« less

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity.

PubMed

Richard-Bulteau, Hélène; Serrurier, Bernard; Crassous, Brigitte; Banzet, Sébastien; Peinnequin, André; Bigard, Xavier; Koulmann, Nathalie

2008-02-01

The present study was designed to test the hypothesis that increasing physical activity by running exercise could favor the recovery of muscle mass after extensive injury and to determine the main molecular mechanisms involved. Left soleus muscles of female Wistar rats were degenerated by notexin injection before animals were assigned to either a sedentary group or an exercised group. Both regenerating and contralateral intact muscles from active and sedentary rats were removed 5, 7, 14, 21, 28 and 42 days after injury (n = 8 rats/group). Increasing contractile activity through running exercise during muscle regeneration ensured the full recovery of muscle mass and muscle cross-sectional area as soon as 21 days after injury, whereas muscle weight remained lower even 42 days postinjury in sedentary rats. Proliferator cell nuclear antigen and MyoD protein expression went on longer in active rats than in sedentary rats. Myogenin protein expression was higher in active animals than in sedentary animals 21 days postinjury. The Akt-mammalian target of rapamycin (mTOR) pathway was activated early during the regeneration process, with further increases of mTOR phosphorylation and its downstream effectors, eukaryotic initiation factor-4E-binding protein-1 and p70(s6k), in active rats compared with sedentary rats (days 7-14). The exercise-induced increase in mTOR phosphorylation, independently of Akt, was associated with decreased levels of phosphorylated AMP-activated protein kinase. Taken together, these results provided evidence that increasing contractile activity during muscle regeneration ensured early and full recovery of muscle mass and suggested that these beneficial effects may be due to a longer proliferative step of myogenic cells and activation of mTOR signaling, independently of Akt, during the maturation step of muscle regeneration.

Thermodynamics of enzyme-catalyzed esterifications: II. Levulinic acid esterification with short-chain alcohols.

PubMed

Altuntepe, Emrah; Emel'yanenko, Vladimir N; Forster-Rotgers, Maximilian; Sadowski, Gabriele; Verevkin, Sergey P; Held, Christoph

2017-10-01

Levulinic acid was esterified with methanol, ethanol, and 1-butanol with the final goal to predict the maximum yield of these equilibrium-limited reactions as function of medium composition. In a first step, standard reaction data (standard Gibbs energy of reaction Δ R g 0 ) were determined from experimental formation properties. Unexpectedly, these Δ R g 0 values strongly deviated from data obtained with classical group contribution methods that are typically used if experimental standard data is not available. In a second step, reaction equilibrium concentrations obtained from esterification catalyzed by Novozym 435 at 323.15 K were measured, and the corresponding activity coefficients of the reacting agents were predicted with perturbed-chain statistical associating fluid theory (PC-SAFT). The so-obtained thermodynamic activities were used to determine Δ R g 0 at 323.15 K. These results could be used to cross-validate Δ R g 0 from experimental formation data. In a third step, reaction-equilibrium experiments showed that equilibrium position of the reactions under consideration depends strongly on the concentration of water and on the ratio of levulinic acid: alcohol in the initial reaction mixtures. The maximum yield of the esters was calculated using Δ R g 0 data from this work and activity coefficients of the reacting agents predicted with PC-SAFT for varying feed composition of the reaction mixtures. The use of the new Δ R g 0 data combined with PC-SAFT allowed good agreement to the measured yields, while predictions based on Δ R g 0 values obtained with group contribution methods showed high deviations to experimental yields.

Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series.

PubMed

Goetz, Matthew B; Bowman, Candice; Hoang, Tuyen; Anaya, Henry; Osborn, Teresa; Gifford, Allen L; Asch, Steven M

2008-03-19

We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis - a point of substantial importance to the VA, which is the largest provider of HIV care in the United States. Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA.Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation. Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3-5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations. This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4).

Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series

PubMed Central

Goetz, Matthew B; Bowman, Candice; Hoang, Tuyen; Anaya, Henry; Osborn, Teresa; Gifford, Allen L; Asch, Steven M

2008-01-01

Background We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis – a point of substantial importance to the VA, which is the largest provider of HIV care in the United States. Methods Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA. Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation. Results Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3–5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations. Discussion This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4). PMID:18353185

Process relevant screening of cellulolytic organisms for consolidated bioprocessing.

PubMed

Antonov, Elena; Schlembach, Ivan; Regestein, Lars; Rosenbaum, Miriam A; Büchs, Jochen

2017-01-01

Although the biocatalytic conversion of cellulosic biomass could replace fossil oil for the production of various compounds, it is often not economically viable due to the high costs of cellulolytic enzymes. One possibility to reduce costs is consolidated bioprocessing (CBP), integrating cellulase production, hydrolysis of cellulose, and the fermentation of the released sugars to the desired product into one process step. To establish such a process, the most suitable cellulase-producing organism has to be identified. Thereby, it is crucial to evaluate the candidates under target process conditions. In this work, the chosen model process was the conversion of cellulose to the platform chemical itaconic acid by a mixed culture of a cellulolytic fungus with Aspergillus terreus as itaconic acid producer. Various cellulase producers were analyzed by the introduced freeze assay that measures the initial carbon release rate, quantifying initial cellulase activity under target process conditions. Promising candidates were then characterized online by monitoring their respiration activity metabolizing cellulose to assess the growth and enzyme production dynamics. The screening of five different cellulase producers with the freeze assay identified Trichoderma   reesei and Penicillium   verruculosum as most promising. The measurement of the respiration activity revealed a retarded induction of cellulase production for P.   verruculosum but a similar cellulase production rate afterwards, compared to T.   reesei . The freeze assay measurement depicted that P.   verruculosum reaches the highest initial carbon release rate among all investigated cellulase producers. After a modification of the cultivation procedure, these results were confirmed by the respiration activity measurement. To compare both methods, a correlation between the measured respiration activity and the initial carbon release rate of the freeze assay was introduced. The analysis revealed that the different initial enzyme/cellulose ratios as well as a discrepancy in cellulose digestibility are the main differences between the two approaches. With two complementary methods to quantify cellulase activity and the dynamics of cellulase production for CBP applications, T.   reesei and P.   verruculosum were identified as compatible candidates for the chosen model process. The presented methods can easily be adapted to screen for suitable cellulose degrading organisms for various other applications.

Master Logic Diagram: An Approach to Identify Initiating Events of HTGRs

NASA Astrophysics Data System (ADS)

Purba, J. H.

2018-02-01

Initiating events of a nuclear power plant being evaluated need to be firstly identified prior to applying probabilistic safety assessment on that plant. Various types of master logic diagrams (MLDs) have been proposedforsearching initiating events of the next generation of nuclear power plants, which have limited data and operating experiences. Those MLDs are different in the number of steps or levels and different in the basis for developing them. This study proposed another type of MLD approach to find high temperature gas cooled reactor (HTGR) initiating events. It consists of five functional steps starting from the top event representing the final objective of the safety functions to the basic event representing the goal of the MLD development, which is an initiating event. The application of the proposed approach to search for two HTGR initiating events, i.e. power turbine generator trip and loss of offsite power, is provided. The results confirmed that the proposed MLD is feasiblefor finding HTGR initiating events.

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

PubMed

Grimm, Sasha S; Isacoff, Ehud Y

2016-04-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis.

Allosteric substrate switching in a voltage sensing lipid phosphatase

PubMed Central

Grimm, Sasha S.; Isacoff, Ehud Y.

2016-01-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We find the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), to have not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage sensing domain (VSD). Using fast FRET reporters of PIPs to monitor enzyme activity and voltage clamp fluorometry to monitor conformational changes in the VSD, we find that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This novel 2-step allosteric control over a dual specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility and endo/exocytosis. PMID:26878552

One-Class Classification-Based Real-Time Activity Error Detection in Smart Homes.

PubMed

Das, Barnan; Cook, Diane J; Krishnan, Narayanan C; Schmitter-Edgecombe, Maureen

2016-08-01

Caring for individuals with dementia is frequently associated with extreme physical and emotional stress, which often leads to depression. Smart home technology and advances in machine learning techniques can provide innovative solutions to reduce caregiver burden. One key service that caregivers provide is prompting individuals with memory limitations to initiate and complete daily activities. We hypothesize that sensor technologies combined with machine learning techniques can automate the process of providing reminder-based interventions. The first step towards automated interventions is to detect when an individual faces difficulty with activities. We propose machine learning approaches based on one-class classification that learn normal activity patterns. When we apply these classifiers to activity patterns that were not seen before, the classifiers are able to detect activity errors, which represent potential prompt situations. We validate our approaches on smart home sensor data obtained from older adult participants, some of whom faced difficulties performing routine activities and thus committed errors.

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation

PubMed Central

Reinhardt, Christoph; von Brühl, Marie-Luise; Manukyan, Davit; Grahl, Lenka; Lorenz, Michael; Altmann, Berid; Dlugai, Silke; Hess, Sonja; Konrad, Ildiko; Orschiedt, Lena; Mackman, Nigel; Ruddock, Lloyd; Massberg, Steffen; Engelmann, Bernd

2008-01-01

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased — and, under conditions of decreased platelet adhesion, PDI inhibition reduced — fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet–secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury. PMID:18274674

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation.

PubMed

Reinhardt, Christoph; von Brühl, Marie-Luise; Manukyan, Davit; Grahl, Lenka; Lorenz, Michael; Altmann, Berid; Dlugai, Silke; Hess, Sonja; Konrad, Ildiko; Orschiedt, Lena; Mackman, Nigel; Ruddock, Lloyd; Massberg, Steffen; Engelmann, Bernd

2008-03-01

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased - and, under conditions of decreased platelet adhesion, PDI inhibition reduced - fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet-secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury.

[Management of rheumatoid arthritis].

PubMed

Fiehn, C; Krüger, K

2016-11-01

Rheumatoid arthritis is the most common inflammatory rheumatic disease. Due to the destruction of joints in the course of the disease it leads to significant morbidity in affected patients. The quality of life and even life expectancy can be severely impaired. Early diagnosis and early initiation of treatment is a decisive step towards a more benign course of the disease. New classification criteria have been published in order to help in early diagnosis. Methods of imaging, such as ultrasound and magnetic resonance imaging help in the detection of synovitis, which is the major pathomorphological manifestation of arthritis and should be identified without any doubt. Treatment follows the rule of treat to target with the aim of achieving remission or if this is not realistic, at least the lowest possible level of disease activity. The first and perhaps most important step in therapy is the initiation of methotrexate or if contraindications are present, another disease-modifying antirheumatic drug (DMARD) as soon as the diagnosis is made. Initial addition of glucocorticoids is recommended, which should be reduced in dose and terminated as soon as possible. Furthermore, either the combination of different DMARDs or the start of biologic DMARDs, such as tumor necrosis factor alpha (TNF-alpha) inhibitors or second generation biologic DMARDs is possible as a treatment option. The treatment follows the rule of shared decision-making and is the standard to treat comorbidities, the use an interdisciplinary approach and to treat functional deficits by rehabilitation measures, such as physiotherapy.

Bridging basic and clinical science with policy studies: The Partners with Transdisciplinary Tobacco Use Research Centers experience.

PubMed

Kobus, Kimberly; Mermelstein, Robin

2009-05-01

The Partners with Transdisciplinary Tobacco Use Research Centers (TTURCs) initiative was a transdisciplinary team-building program, funded by the Robert Wood Johnson Foundation, to expand the policy research capacity of the TTURCs. EXPANSION INTO POLICY RESEARCh: Policy research activities at the TTURCs fell into four broad domains: (a) health services research, (b) examination of the business case for cessation treatment and funding, (c) collaborative teams with key stakeholders, and (d) direct assessment of smoking-related policies. Examples of each domain are presented. Goals of the initiative included efforts to foster collaborative, transdisciplinary research, to bring new investigators into the field, to develop programs of policy research, to answer next-step translational questions, and to enhance awareness of policy relevance. Success at meeting each of these goals is discussed. We offer recommendations for incorporating programs of policy research into full-spectrum transdisciplinary research initiatives, including the roles of research teams, senior researchers, infrastructure, stakeholders, and communications activities. The TTURC Partners initiative represented a first-generation effort to fill the gap between scientific discovery and research translation through expansion into policy studies. While all aspects of the effort were not equally successful, the effort demonstrated that it is possible to develop successful collaborations that extend more basic and applied research into studies that examine their policy and practice implications.

An inhibitor of eIF2 activity in the sRNA pool of eukaryotic cells.

PubMed

Centrella, Michael; Porter, David L; McCarthy, Thomas L

2011-08-15

Eukaryotic protein synthesis is a multi-step and highly controlled process that includes an early initiation complex containing eukaryotic initiation factor 2 (eIF2), GTP, and methionine-charged initiator methionyl-tRNA (met-tRNAi). During studies to reconstruct formation of the ternary complex containing these molecules, we detected a potent inhibitor in low molecular mass RNA (sRNA) preparations of eukaryotic tRNA. The ternary complex inhibitor (TCI) was retained in the total sRNA pool after met-tRNAi was charged by aminoacyl tRNA synthetase, co-eluted with sRNA by size exclusion chromatography, but resolved from met-tRNAi by ion exchange chromatography. The adverse effect of TCI was not overcome by high GTP or magnesium omission and was independent of GTP regeneration. Rather, TCI suppressed the rate of ternary complex formation, and disrupted protein synthesis and the accumulation of heavy polymeric ribosomes in reticulocyte lysates in vitro. Lastly, a component or components in ribosome depleted cell lysate significantly reversed TCI activity. Since assembly of the met-tRNAi/eIF2/GTP ternary complex is integral to protein synthesis, awareness of TCI is important to avoid confusion in studies of translation initiation. A clear definition of TCI may also allow a better appreciation of physiologic or pathologic situations, factors, and events that control protein synthesis in vivo. Copyright © 2011 Elsevier B.V. All rights reserved.

Extending the DIDEO ontology to include entities from the natural product drug interaction domain of discourse.

PubMed

Judkins, John; Tay-Sontheimer, Jessica; Boyce, Richard D; Brochhausen, Mathias

2018-05-09

Prompted by the frequency of concomitant use of prescription drugs with natural products, and the lack of knowledge regarding the impact of pharmacokinetic-based natural product-drug interactions (PK-NPDIs), the United States National Center for Complementary and Integrative Health has established a center of excellence for PK-NPDI. The Center is creating a public database to help researchers (primarly pharmacologists and medicinal chemists) to share and access data, results, and methods from PK-NPDI studies. In order to represent the semantics of the data and foster interoperability, we are extending the Drug-Drug Interaction and Evidence Ontology (DIDEO) to include definitions for terms used by the data repository. This is feasible due to a number of similarities between pharmacokinetic drug-drug interactions and PK-NPDIs. To achieve this, we set up an iterative domain analysis in the following steps. In Step 1 PK-NPDI domain experts produce a list of terms and definitions based on data from PK-NPDI studies, in Step 2 an ontology expert creates ontologically appropriate classes and definitions from the list along with class axioms, in Step 3 there is an iterative editing process during which the domain experts and the ontology experts review, assess, and amend class labels and definitions and in Step 4 the ontology expert implements the new classes in the DIDEO development branch. This workflow often results in different labels and definitions for the new classes in DIDEO than the domain experts initially provided; the latter are preserved in DIDEO as separate annotations. Step 1 resulted in a list of 344 terms. During Step 2 we found that 9 of these terms already existed in DIDEO, and 6 existed in other OBO Foundry ontologies. These 6 were imported into DIDEO; additional terms from multiple OBO Foundry ontologies were also imported, either to serve as superclasses for new terms in the initial list or to build axioms for these terms. At the time of writing, 7 terms have definitions ready for review (Step 2), 64 are ready for implementation (Step 3) and 112 have been pushed to DIDEO (Step 4). Step 2 also suggested that 26 terms of the original list were redundant and did not need implementation; the domain experts agreed to remove them. Step 4 resulted in many terms being added to DIDEO that help to provide an additional layer of granularity in describing experimental conditions and results, e.g. transfected cultured cells used in metabolism studies and chemical reactions used in measuring enzyme activity. These terms also were integrated into the NaPDI repository. We found DIDEO to provide a sound foundation for semantic representation of PK-NPDI terms, and we have shown the novelty of the project in that DIDEO is the only ontology in which NPDI terms are formally defined.

Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors

NASA Astrophysics Data System (ADS)

Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

2015-05-01

In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

Molecular mechanism of ERK dephosphorylation by striatal-enriched protein tyrosine phosphatase (STEP)

PubMed Central

Li, Hui; Li, Kang-shuai; Su, Jing; Chen, Lai-Zhong; Xu, Yun-Fei; Wang, Hong-Mei; Gong, Zheng; Cui, Guo-Ying; Yu, Xiao; Wang, Kai; Yao, Wei; Xin, Tao; Li, Min-Yong; Xiao, Kun-Hong; An, Xiao-fei; Huo, Yuqing; Xu, Zhi-gang; Sun, Jin-Peng; Pang, Qi

2013-01-01

Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward pNPP, phospho-tyrosine-containing peptides, and the full-length phospho-ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N-terminal regulatory region and key residues in its active site. Specifically, both KIM and KIS of STEP were required for ERK interaction. In addition to the N-terminal KIS region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho-ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho-ERK peptide sequence through its active site, and the contact of STEP F311 with phospho-ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP-ERK recognition, which could serve as a potential therapy for neurological disorders. PMID:24117863

Reduced Order Models for Reactions of Energetic Materials

NASA Astrophysics Data System (ADS)

Kober, Edward

The formulation of reduced order models for the reaction chemistry of energetic materials under high pressures is needed for the development of mesoscale models in the areas of initiation, deflagration and detonation. Phenomenologically, 4-8 step models have been formulated from the analysis of cook-off data by analyzing the temperature rise of heated samples. Reactive molecular dynamics simulations have been used to simulate many of these processes, but reducing the results of those simulations to simple models has not been achieved. Typically, these efforts have focused on identifying molecular species and detailing specific chemical reactions. An alternative approach is presented here that is based on identifying the coordination geometries of each atom in the simulation and tracking classes of reactions by correlated changes in these geometries. Here, every atom and type of reaction is documented for every time step; no information is lost from unsuccessful molecular identification. Principal Component Analysis methods can then be used to map out the effective chemical reaction steps. For HMX and TATB decompositions simulated with ReaxFF, 90% of the data can be explained by 4-6 steps, generating models similar to those from the cook-off analysis. By performing these simulations at a variety of temperatures and pressures, both the activation and reaction energies and volumes can then be extracted.

Effects of various light curing methods on the leachability of uncured substances and hardness of a composite resin.

PubMed

Moon, H-J; Lee, Y-K; Lim, B-S; Kim, C-W

2004-03-01

The purpose of this study was to evaluate the effect of the various light curing units (plasma arc, halogen and light-emitting diodes) and irradiation methods (one-step, two-step and pulse) using different light energy densities on the leachability of unreacted monomers (Bis-GMA and UDMA) and the surface hardness of a composite resin (Z250, 3M). Leachability of the specimens immersed for 7 days in ethanol was analysed by HPLC. Vicker's hardness number (VHN) was measured immediately after curing (IC) and after immersion in ethanol for 7 days. Various irradiation methods with three curing units resulted in differences in the amount of leached monomers and VHN of IC when light energy density was lower than 17.0 J cm(-2) (P = 0.05). However, regardless of curing units and irradiation methods, these results were not different when the time or light energy density increased. When similar light energy density was irradiated (15.6-17.7 J cm(-2)), the efficiency of irradiation methods was different by the following order: one-step > or = two-step > pulse. These results suggest that the amount of leached monomers and VHN were influenced by forming polymer structure in activation and initiation stages of polymerization process with different light source energies and curing times.

Response of deformation patterns to reorganization of the southern San Andreas fault system since ca. 1.5 Ma

NASA Astrophysics Data System (ADS)

Fattaruso, Laura A.; Cooke, Michele L.; Dorsey, Rebecca J.; Housen, Bernard A.

2016-12-01

Between 1.5 and 1.1 Ma, the southern San Andreas fault system underwent a major reorganization that included initiation of the San Jacinto fault zone and termination of slip on the extensional West Salton detachment fault. The southern San Andreas fault itself has also evolved since this time, with several shifts in activity among fault strands within San Gorgonio Pass. We use three-dimensional mechanical Boundary Element Method models to investigate the impact of these changes to the fault network on deformation patterns. A series of snapshot models of the succession of active fault geometries explore the role of fault interaction and tectonic loading in abandonment of the West Salton detachment fault, initiation of the San Jacinto fault zone, and shifts in activity of the San Andreas fault. Interpreted changes to uplift patterns are well matched by model results. These results support the idea that initiation and growth of the San Jacinto fault zone led to increased uplift rates in the San Gabriel Mountains and decreased uplift rates in the San Bernardino Mountains. Comparison of model results for vertical-axis rotation to data from paleomagnetic studies reveals a good match to local rotation patterns in the Mecca Hills and Borrego Badlands. We explore the mechanical efficiency at each step in the modeled fault evolution, and find an overall trend toward increased efficiency through time. Strain energy density patterns are used to identify regions of incipient faulting, and support the notion of north-to-south propagation of the San Jacinto fault during its initiation.

Quantitative modeling of the molecular steps underlying shut-off of rhodopsin activity in rod phototransduction

PubMed Central

Kraft, Timothy W.

2016-01-01

Purpose To examine the predictions of alternative models for the stochastic shut-off of activated rhodopsin (R*) and their implications for the interpretation of experimentally recorded single-photon responses (SPRs) in mammalian rods. Theory We analyze the transitions that an activated R* molecule undergoes as a result of successive phosphorylation steps and arrestin binding. We consider certain simplifying cases for the relative magnitudes of the reaction rate constants and derive the probability distributions for the time to arrestin binding. In addition to the conventional model in which R* catalytic activity declines in a graded manner with successive phosphorylations, we analyze two cases in which the activity is assumed to occur not via multiple small steps upon each phosphorylation but via a single large step. We refer to these latter two cases as the binary R* shut-off and three-state R* shut-off models. Methods We simulate R*’s stochastic reactions numerically for the three models. In the simplifying cases for the ratio of rate constants in the binary and three-state models, we show that the probability distribution of the time to arrestin binding is accurately predicted. To simulate SPRs, we then integrate the differential equations for the downstream reactions using a standard model of the rod outer segment that includes longitudinal diffusion of cGMP and Ca2+. Results Our simulations of SPRs in the conventional model of graded shut-off of R* conform closely to the simulations in a recent study. However, the gain factor required to account for the observed mean SPR amplitude is higher than can be accounted for from biochemical experiments. In addition, a substantial minority of the simulated SPRs exhibit features that have not been reported in published experiments. Our simulations of SPRs using the model of binary R* shut-off appear to conform closely to experimental results for wild type (WT) mouse rods, and the required gain factor conforms to biochemical expectations. However, for the arrestin knockout (Arr−/−) phenotype, the predictions deviated from experimental findings and led us to invoke a low-activity state that R* enters before arrestin binding. Our simulations of this three-state R* shut-off model are very similar to those of the binary model in the WT case but are preferred because they appear to accurately predict the mean SPRs for four mutant phenotypes, Arr+/−, Arr−/−, GRK1+/−, and GRK1−/−, in addition to the WT phenotype. When we additionally treated the formation and shut-off of activated phosphodiesterase (E*) as stochastic, the simulated SPRs appeared even more similar to real SPRs, and there was very little change in the ensemble mean and standard deviation or in the amplitude distribution. Conclusions We conclude that the conventional model of graded reduction in R* activity through successive phosphorylation steps appears to be inconsistent with experimental results. Instead, we find that two variants of a model in which R* activity initially remains high and then declines abruptly after several phosphorylation steps appears capable of providing a better description of experimentally measured SPRs. PMID:27375353

Auxotonic to isometric contraction transitioning in a beating heart causes myosin step-size to down shift

PubMed Central

Sun, Xiaojing; Wang, Yihua; Ajtai, Katalin

2017-01-01

Myosin motors in cardiac ventriculum convert ATP free energy to the work of moving blood volume under pressure. The actin bound motor cyclically rotates its lever-arm/light-chain complex linking motor generated torque to the myosin filament backbone and translating actin against resisting force. Previous research showed that the unloaded in vitro motor is described with high precision by single molecule mechanical characteristics including unitary step-sizes of approximately 3, 5, and 8 nm and their relative step-frequencies of approximately 13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin essential light chain (ELC) N-terminus actin binding. Step-size and step-frequency quantitation specifies in vitro motor function including duty-ratio, power, and strain sensitivity metrics. In vivo, motors integrated into the muscle sarcomere form the more complex and hierarchically functioning muscle machine. The goal of the research reported here is to measure single myosin step-size and step-frequency in vivo to assess how tissue integration impacts motor function. A photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in the beating heart of a live zebrafish embryo. Detected single GFP emission reports time-resolved myosin lever-arm orientation interpreted as step-size and step-frequency providing single myosin mechanical characteristics over the active cycle. Following step-frequency of cardiac ventriculum myosin transitioning from low to high force in relaxed to auxotonic to isometric contraction phases indicates that the imposition of resisting force during contraction causes the motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in the near-isometric phase. At peak force, the ATP initiated actomyosin dissociation is the predominant strain inhibited transition in the native myosin contraction cycle. The proposed model for motor down-shifting and strain sensing involves ELC N-terminus actin binding. Overall, the approach is a unique bottom-up single molecule mechanical characterization of a hierarchically functional native muscle myosin. PMID:28423017

Ubiquitin and Proteasomes in Transcription

PubMed Central

Geng, Fuqiang; Wenzel, Sabine; Tansey, William P.

2013-01-01

Regulation of gene transcription is vitally important for the maintenance of normal cellular homeostasis. Failure to correctly regulate gene expression, or to deal with problems that arise during the transcription process, can lead to cellular catastrophe and disease. One of the ways cells cope with the challenges of transcription is by making extensive use of the proteolytic and nonproteolytic activities of the ubiquitin-proteasome system (UPS). Here, we review recent evidence showing deep mechanistic connections between the transcription and ubiquitin-proteasome systems. Our goal is to leave the reader with a sense that just about every step in transcription—from transcription initiation through to export of mRNA from the nucleus—is influenced by the UPS and that all major arms of the system—from the first step in ubiquitin (Ub) conjugation through to the proteasome—are recruited into transcriptional processes to provide regulation, directionality, and deconstructive power. PMID:22404630

Cobalt catalyzed carbonylation of unactivated C(sp3)–H bonds† †Electronic supplementary information (ESI) available. CCDC 1507203 (2t) & 1507204 (2a). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc05026c Click here for additional data file. Click here for additional data file.

PubMed Central

Barsu, Nagaraju; Bolli, Shyam Kumar

2017-01-01

A general efficient regioselective cobalt catalyzed carbonylation of unactivated C(sp3)–H bonds of aliphatic amides was demonstrated using atmospheric (1–2 atm) carbon monoxide as a C1 source. This straightforward approach provides access to α-spiral succinimide regioselectively in a good yield. Cobalt catalyzed sp3 C–H bond carbonylation is reported for the first time including the functionalization of (β)-C–H bonds of α-1°, 2°, 3° carbons and even internal (β)-C–H bonds. Our initial mechanistic investigation reveals that the C–H activation step is irreversible and will possibly be the rate determining step. PMID:28451350

Well-Defined Models for the Elusive Dinuclear Intermediates of the Pauson-Khand Reaction.

PubMed

Hartline, Douglas R; Zeller, Matthias; Uyeda, Christopher

2016-05-10

The mechanism of the Pauson-Khand reaction has attracted significant interest due to the unusual dinuclear nature of the Co2 (CO)x active site. Experimental and computational data have indicated that the intermediates following the initial Co2 (CO)6 (alkyne) complex are thermodynamically unstable and do not build up in appreciable concentrations during the course of the reaction. As a consequence, the key steps that control the scope of viable substrates and various aspects of selectivity have remained largely uncharacterized. Herein, a direct experimental investigation of the dinuclear metallacycle-forming step of the Pauson-Khand reaction is reported. These studies capitalize on well-defined d(9) -d(9) dinickel complexes supported by a naphthyridine-diimine (NDI) pincer ligand as functional surrogates of Co2 (CO)8 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Report of the In Situ Resources Utilization Workshop

NASA Technical Reports Server (NTRS)

Fairchild, Kyle (Editor); Mendell, Wendell W. (Editor)

1988-01-01

The results of a workshop of 50 representatives from the public and private sector which investigated the potential joint development of the key technologies and mechanisms that will enable the permanent habitation of space are presented. The workshop is an initial step to develop a joint public/private assessment of new technology requirements of future space options, to share knowledge on required technologies that may exist in the private sector, and to investigate potential joint technology development opportunities. The majority of the material was produced in 5 working groups: (1) Construction, Assembly, Automation and Robotics; (2) Prospecting, Mining, and Surface Transportation; (3) Biosystems and Life Support; (4) Materials Processing; and (5) Innovative Ventures. In addition to the results of the working groups, preliminary technology development recommendations to assist in near-term development priority decisions are presented. Finally, steps are outlined for potential new future activities and relationships among the public, private, and academic sectors.

Comparison of the Anti-Adhesion Activity of Three Different Cranberry Extracts on Uropathogenic P-fimbriated Escherichia coli: a Randomized, Double-blind, Placebo Controlled, Ex Vivo, Acute Study.

PubMed

Howell, Amy; Souza, Dan; Roller, Marc; Fromentin, Emilie

2015-07-01

Research suggests that cranberry (Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine. from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo.

Automated assay for screening the enzymatic release of reducing sugars from micronized biomass.

PubMed

Navarro, David; Couturier, Marie; da Silva, Gabriela Ghizzi Damasceno; Berrin, Jean-Guy; Rouau, Xavier; Asther, Marcel; Bignon, Christophe

2010-07-16

To reduce the production cost of bioethanol obtained from fermentation of the sugars provided by degradation of lignocellulosic biomass (i.e., second generation bioethanol), it is necessary to screen for new enzymes endowed with more efficient biomass degrading properties. This demands the set-up of high-throughput screening methods. Several methods have been devised all using microplates in the industrial SBS format. Although this size reduction and standardization has greatly improved the screening process, the published methods comprise one or more manual steps that seriously decrease throughput. Therefore, we worked to devise a screening method devoid of any manual steps. We describe a fully automated assay for measuring the amount of reducing sugars released by biomass-degrading enzymes from wheat-straw and spruce. The method comprises two independent and automated steps. The first step is the making of "substrate plates". It consists of filling 96-well microplates with slurry suspensions of micronized substrate which are then stored frozen until use. The second step is an enzymatic activity assay. After thawing, the substrate plates are supplemented by the robot with cell-wall degrading enzymes where necessary, and the whole process from addition of enzymes to quantification of released sugars is autonomously performed by the robot. We describe how critical parameters (amount of substrate, amount of enzyme, incubation duration and temperature) were selected to fit with our specific use. The ability of this automated small-scale assay to discriminate among different enzymatic activities was validated using a set of commercial enzymes. Using an automatic microplate sealer solved three main problems generally encountered during the set-up of methods for measuring the sugar-releasing activity of plant cell wall-degrading enzymes: throughput, automation, and evaporation losses. In its present set-up, the robot can autonomously process 120 triplicate wheat-straw samples per day. This throughput can be doubled if the incubation time is reduced from 24 h to 4 h (for initial rates measurements, for instance). This method can potentially be used with any insoluble substrate that is micronizable. A video illustrating the method can be seen at the following URL: http://www.youtube.com/watch?v=NFg6TxjuMWU.

How many steps/day are enough? For older adults and special populations

PubMed Central

2011-01-01

Older adults and special populations (living with disability and/or chronic illness that may limit mobility and/or physical endurance) can benefit from practicing a more physically active lifestyle, typically by increasing ambulatory activity. Step counting devices (accelerometers and pedometers) offer an opportunity to monitor daily ambulatory activity; however, an appropriate translation of public health guidelines in terms of steps/day is unknown. Therefore this review was conducted to translate public health recommendations in terms of steps/day. Normative data indicates that 1) healthy older adults average 2,000-9,000 steps/day, and 2) special populations average 1,200-8,800 steps/day. Pedometer-based interventions in older adults and special populations elicit a weighted increase of approximately 775 steps/day (or an effect size of 0.26) and 2,215 steps/day (or an effect size of 0.67), respectively. There is no evidence to inform a moderate intensity cadence (i.e., steps/minute) in older adults at this time. However, using the adult cadence of 100 steps/minute to demark the lower end of an absolutely-defined moderate intensity (i.e., 3 METs), and multiplying this by 30 minutes produces a reasonable heuristic (i.e., guiding) value of 3,000 steps. However, this cadence may be unattainable in some frail/diseased populations. Regardless, to truly translate public health guidelines, these steps should be taken over and above activities performed in the course of daily living, be of at least moderate intensity accumulated in minimally 10 minute bouts, and add up to at least 150 minutes over the week. Considering a daily background of 5,000 steps/day (which may actually be too high for some older adults and/or special populations), a computed translation approximates 8,000 steps on days that include a target of achieving 30 minutes of moderate-to-vigorous physical activity (MVPA), and approximately 7,100 steps/day if averaged over a week. Measured directly and including these background activities, the evidence suggests that 30 minutes of daily MVPA accumulated in addition to habitual daily activities in healthy older adults is equivalent to taking approximately 7,000-10,000 steps/day. Those living with disability and/or chronic illness (that limits mobility and or/physical endurance) display lower levels of background daily activity, and this will affect whole-day estimates of recommended physical activity. PMID:21798044

Baby-Friendly Hospital Initiative: evaluation of the Ten Steps to Successful Breastfeeding

PubMed Central

Lopes, Soraia da Silva; Laignier, Mariana Rabello; Primo, Cândida Caniçali; Leite, Franciéle Marabotti C.

2013-01-01

OBJECTIVE: To asses the performance of the Ten Steps to Successful Breastfeeding in an university hospital. METHODS: Descriptive and quantitative research, in which 103 people were interviewed in the outpatient prenatal clinic, in the maternity-ward and in the Neonatal Intensive Care Unit of a university hospital in Vitória, Southeast Brazil. The "Institutional Self-Evaluation Questionnaire" of the Baby Friendly Hospital Initiative was applied. Using this tool, the outcome was measured by the concordance index (CI) proposed by the World Health Organization and by the United Nations Children's Fund. RESULTS: Although the hospital does not have a policy that addresses promotion, protection and support for breastfeeding, 93.3% of the mothers had contact with their babies immediately after birth (step 4), 83.3% of the professionals guided mothers how to breastfeed (step 5), 86.6% of the neonates did not receive any food or drink other than breast milk (step 6), 100% of babies were housed together with their mothers (step 7), 83.3% of the women were encouraged for breastfeeding on demand (step 8) and 100% of the infants did not use bottles or pacifiers (step 9). CONCLUSIONS: 60% of the steps were completed by the hospital. The greatest difficulty was to inform pregnant women about the importance and the management of breastfeeding (step 3). Therefore, visits to pregnant women are recommended, in order to prepare them for breastfeeding and to explain about the infants' healthy feeding habits. PMID:24473954

Achieving the daily step goal of 10,000 steps: the experience of a Canadian family attached to pedometers.

PubMed

Choi, Bernard C K; Pak, Anita W P; Choi, Jerome C L; Choi, Elaine C L

2007-01-01

Health experts recommend daily step goals of 10,000 steps for adults and 12,000 steps for youths to achieve a healthy active living. This article reports the findings of a Canadian family project to investigate whether the recommended daily step goals are achievable in a real life setting, and suggests ways to increase the daily steps to meet the goal. The family project also provides an example to encourage more Canadians to conduct family projects on healthy living. This is a pilot feasibility study. A Canadian family was recruited for the study, with 4 volunteers (father, mother, son and daughter). Each volunteer was asked to wear a pedometer and to record daily steps for three time periods of each day during a 2-month period. Both minimal routine steps, and additional steps from special non-routine activities, were recorded at work, school and home. The mean number of daily steps from routine minimal daily activities for the family was 6685 steps in a day (16 hr, approx 400 steps/hr). There was thus a mean deficit of 4315 steps per day, or approximately 30,000 steps per week, from the goal (10,000 steps for adults; 12,000 steps for youths). Special activities that were found to effectively increase the steps above the routine level include: walking at brisk pace, grocery shopping, window shopping in a mall, going to an entertainment centre, and attending parties (such as to celebrate the holiday season and birthdays). To increase our daily steps to meet the daily step goal, a new culture is recommended: "get off the chair". By definition, sitting on a chair precludes the opportunity to walk. We encourage people to get off the chair, to go shopping, and to go partying, as a practical and fun way to increase the daily steps. This paper is a call for increased physical activity to meet the daily step goal.

Translatome analysis at the egg-to-embryo transition in sea urchin

PubMed Central

Chassé, Héloïse; Aubert, Julie; Boulben, Sandrine; Le Corguillé, Gildas; Corre, Erwan; Cormier, Patrick

2018-01-01

Abstract Early embryogenesis relies on the translational regulation of maternally stored mRNAs. In sea urchin, fertilization triggers a dramatic rise in translation activity, necessary for the onset of cell division. Here, the full spectrum of the mRNAs translated upon fertilization was investigated by polysome profiling and sequencing. The translatome of the early sea urchin embryo gave a complete picture of the polysomal recruitment dynamics following fertilization. Our results indicate that only a subset of maternal mRNAs were selectively recruited onto polysomes, with over-represented functional categories in the translated set. The increase in translation upon fertilization depends on the formation of translation initiation complexes following mTOR pathway activation. Surprisingly, mTOR pathway inhibition differentially affected polysomal recruitment of the newly translated mRNAs, which thus appeared either mTOR-dependent or mTOR-independent. Therefore, our data argue for an alternative to the classical cap-dependent model of translation in early development. The identification of the mRNAs translated following fertilization helped assign translational activation events to specific mRNAs. This translatome is the first step to a comprehensive analysis of the molecular mechanisms governing translation upon fertilization and the translational regulatory networks that control the egg-to-embryo transition as well as the early steps of embryogenesis. PMID:29660001

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

PubMed Central

Pavlov, Tengis S.; Ilatovskaya, Daria V.; Palygin, Oleg; Levchenko, Vladislav; Pochynyuk, Oleh; Staruschenko, Alexander

2015-01-01

Cyst initiation and expansion during polycystic kidney disease is a complex process characterized by abnormalities in tubular cell proliferation, luminal fluid accumulation and extracellular matrix formation. Activity of ion channels and intracellular calcium signaling are key physiologic parameters which determine functions of tubular epithelium. We developed a method suitable for real-time observation of ion channels activity with patch-clamp technique and registration of intracellular Ca2+ level in epithelial monolayers freshly isolated from renal cysts. PCK rats, a genetic model of autosomal recessive polycystic kidney disease (ARPKD), were used here for ex vivo analysis of ion channels and calcium flux. Described here is a detailed step-by-step procedure designed to isolate cystic monolayers and non-dilated tubules from PCK or normal Sprague Dawley (SD) rats, and monitor single channel activity and intracellular Ca2+ dynamics. This method does not require enzymatic processing and allows analysis in a native setting of freshly isolated epithelial monolayer. Moreover, this technique is very sensitive to intracellular calcium changes and generates high resolution images for precise measurements. Finally, isolated cystic epithelium can be further used for staining with antibodies or dyes, preparation of primary cultures and purification for various biochemical assays. PMID:26381526

Mating-Induced Shedding of Cell Walls, Removal of Walls from Vegetative Cells, and Osmotic Stress Induce Presumed Cell Wall Genes in Chlamydomonas1

PubMed Central

Hoffmann, Xenia-Katharina; Beck, Christoph F.

2005-01-01

The first step in sexual differentiation of the unicellular green alga Chlamydomonas reinhardtii is the formation of gametes. Three genes, GAS28, GAS30, and GAS31, encoding Hyp-rich glycoproteins that presumably are cell wall constituents, are expressed in the late phase of gametogenesis. These genes, in addition, are activated by zygote formation and cell wall removal and by the application of osmotic stress. The induction by zygote formation could be traced to cell wall shedding prior to gamete fusion since it was seen in mutants defective in cell fusion. However, it was absent in mutants defective in the initial steps of mating, i.e. in flagellar agglutination and in accumulation of adenosine 3′,5′-cyclic monophosphate in response to this agglutination. Induction of the three GAS genes was also observed when cultures were exposed to hypoosmotic or hyperosmotic stress. To address the question whether the induction seen upon cell wall removal from both gametes and vegetative cells was elicited by osmotic stress, cell wall removal was performed under isosmotic conditions. Also under such conditions an activation of the genes was observed, suggesting that the signaling pathway(s) is (are) activated by wall removal itself. PMID:16183845

Development of a hardware-based AC microgrid for AC stability assessment

NASA Astrophysics Data System (ADS)

Swanson, Robert R.

As more power electronic-based devices enable the development of high-bandwidth AC microgrids, the topic of microgrid power distribution stability has become of increased interest. Recently, researchers have proposed a relatively straightforward method to assess the stability of AC systems based upon the time-constants of sources, the net bus capacitance, and the rate limits of sources. In this research, a focus has been to develop a hardware test system to evaluate AC system stability. As a first step, a time domain model of a two converter microgrid was established in which a three phase inverter acts as a power source and an active rectifier serves as an adjustable constant power AC load. The constant power load can be utilized to create rapid power flow transients to the generating system. As a second step, the inverter and active rectifier were designed using a Smart Power Module IGBT for switching and an embedded microcontroller as a processor for algorithm implementation. The inverter and active rectifier were designed to operate simultaneously using a synchronization signal to ensure each respective local controller operates in a common reference frame. Finally, the physical system was created and initial testing performed to validate the hardware functionality as a variable amplitude and variable frequency AC system.

Strategies and Policies for Space - Indian Perspective

NASA Astrophysics Data System (ADS)

Kasturirangan, K.; Sridhara Murthy, K. R.; Sundararmiah, V.; Rao, Mukund

2002-01-01

Indian Space Program, which was established as government effort about three decades ago has become a major force in providing vital services for social and economic sectors in India in the fields of satellite telecommunications, television broadcasting, meteorological services and remote sensing of natural resources. Capabilities have been developed over the years, following a step-by-step process to develop and operate space infrastructure in India, including state-of-the-art satellites and satellite launch vehicles. In carrying out these developments, Indian Space Research Organisation, which is the national agency responsible for space activities under Government of India, develop policies and programs, which promoted industrial participation in variety of space activities including manufacture of space hardware, conduct of value added activities and provision of services involving space systems. Policy initiatives have also been taken recently to promote private sector participation in the establishment of Indian Satellite Systems for telecommunications. Strategic alliances have also been developed with international space industries for marketing of services such as remote sensing data. The paper traces evaluation of the policies towards development of industrial participation in space and future transition into commercial space enterprise. Policy issues concerning the national requirements vis-à-vis the international environment will also be discussed to analyze the strategies for international cooperation.

Translatome analysis at the egg-to-embryo transition in sea urchin.

PubMed

Chassé, Héloïse; Aubert, Julie; Boulben, Sandrine; Le Corguillé, Gildas; Corre, Erwan; Cormier, Patrick; Morales, Julia

2018-05-18

Early embryogenesis relies on the translational regulation of maternally stored mRNAs. In sea urchin, fertilization triggers a dramatic rise in translation activity, necessary for the onset of cell division. Here, the full spectrum of the mRNAs translated upon fertilization was investigated by polysome profiling and sequencing. The translatome of the early sea urchin embryo gave a complete picture of the polysomal recruitment dynamics following fertilization. Our results indicate that only a subset of maternal mRNAs were selectively recruited onto polysomes, with over-represented functional categories in the translated set. The increase in translation upon fertilization depends on the formation of translation initiation complexes following mTOR pathway activation. Surprisingly, mTOR pathway inhibition differentially affected polysomal recruitment of the newly translated mRNAs, which thus appeared either mTOR-dependent or mTOR-independent. Therefore, our data argue for an alternative to the classical cap-dependent model of translation in early development. The identification of the mRNAs translated following fertilization helped assign translational activation events to specific mRNAs. This translatome is the first step to a comprehensive analysis of the molecular mechanisms governing translation upon fertilization and the translational regulatory networks that control the egg-to-embryo transition as well as the early steps of embryogenesis.

Lateral stepping for postural correction in Parkinson's disease.

PubMed

King, Laurie A; Horak, Fay B

2008-03-01

To characterize the lateral stepping strategies for postural correction in patients with Parkinson's disease (PD) and the effect of their anti-parkinson medication. Observational study. Outpatient neuroscience laboratory. Thirteen participants with idiopathic PD in their on (PD on) and off (PD off) levodopa state and 14 healthy elderly controls. Movable platform with lateral translations of 12 cm at 14.6 cm/s ramp velocity. The incidence and characteristics of 3 postural strategies were observed: lateral side-step, crossover step, or no step. Corrective stepping was characterized by latency to step after perturbation onset, step velocity, and step length and presence of an anticipatory postural adjustment (APA). Additionally, percentages of trials resulting in falls were identified for each group. Whereas elderly control participants never fell, PD participants fell in 24% and 35% of trials in the on and off medication states, respectively. Both PD and control participants most often used a lateral side-step strategy; 70% (control), 67% (PD off), and 73% (PD on) of all trials, respectively. PD participants fell most often when using a crossover strategy (75% of all crossover trials) or no-step strategy (100% of all no-step trials). In the off medication state, PD participants' lateral stepping strategies were initiated later than controls (370+/-37 ms vs 280+/-10 ms, P<.01), and steps were smaller (254+/-20 mm vs 357+/-17 mm, P<.01) and slower (0.99+/-0.08 m/s vs 1.20+/-0.07 m/s, P<.05). No differences were found between the PD off versus PD on state in the corrective stepping characteristics. Unlike control participants, PD participants often (56% of side-step strategy trials) failed to activate an APA before stepping, although their APAs, when present, were of similar latency and magnitude as for control participants. Levodopa on or off state did not significantly affect falls, APAs, or lateral step latency, velocity, or amplitude (P>.05). PD participants showed significantly more postural instability and falls than age-matched controls when stepping was required for postural correction in response to lateral disequilibrium. Although PD participants usually used a similar lateral stepping strategy as controls in response to lateral translations, lack of an anticipatory lateral weight shift, and bradykinetic characteristics of the stepping responses help explain the greater rate of falls in participants with PD. Differences were not found between the levodopa on and off states. The results suggest that rehabilitation aimed at improving lateral stability in PD should include facilitating APAs before a lateral side-stepping strategy with faster and larger steps to recover equilibrium.

Effects of interventions on normalizing step width during self-paced dual-belt treadmill walking with virtual reality, a randomised controlled trial.

PubMed

Oude Lansink, I L B; van Kouwenhove, L; Dijkstra, P U; Postema, K; Hijmans, J M

2017-10-01

Step width is increased during dual-belt treadmill walking, in self-paced mode with virtual reality. Generally a familiarization period is thought to be necessary to normalize step width. The aim of this randomised study was to analyze the effects of two interventions on step width, to reduce the familiarization period. We used the GRAIL (Gait Real-time Analysis Interactive Lab), a dual-belt treadmill with virtual reality in the self-paced mode. Thirty healthy young adults were randomly allocated to three groups and asked to walk at their preferred speed for 5min. In the first session, the control-group received no intervention, the 'walk-on-the-line'-group was instructed to walk on a line, projected on the between-belt gap of the treadmill and the feedback-group received feedback about their current step width and were asked to reduce it. Interventions started after 1min and lasted 1min. During the second session, 7-10days later, no interventions were given. Linear mixed modeling showed that interventions did not have an effect on step width after the intervention period in session 1. Initial step width (second 30s) of session 1 was larger than initial step width of session 2. Step width normalized after 2min and variation in step width stabilized after 1min. Interventions do not reduce step width after intervention period. A 2-min familiarization period is sufficient to normalize and stabilize step width, in healthy young adults, regardless of interventions. A standardized intervention to normalize step width is not necessary. Copyright © 2017 Elsevier B.V. All rights reserved.

TRF2/RAP1 and DNA–PK mediate a double protection against joining at telomeric ends

PubMed Central

Bombarde, Oriane; Boby, Céline; Gomez, Dennis; Frit, Philippe; Giraud-Panis, Marie-Josèphe; Gilson, Eric; Salles, Bernard; Calsou, Patrick

2010-01-01

DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA–PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA–PK end binding and activation step and (2) DNA–PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells. PMID:20407424

Transcription regulation by the Mediator complex.

PubMed

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

Wash-away of contaminant downstream of a backward-facing step over a range of Schmidt number

NASA Astrophysics Data System (ADS)

Min, Hannah; Fischer, Paul F.; Pearlstein, Arne J.

2017-11-01

We report computations of two-dimensional unsteady convective mass transfer in flow over a backward-facing step, in which a contaminant initially present downstream of the step is ``washed away''. Results are presented for a range of Schmidt numbers, showing how the recirculation region downstream of the step not only serves to retain contaminant near the step, but also transports contaminant upstream towards the step. The results for the highest Schmidt number considered (2650) are relevant to wash-away of low-molecular weight species in liquids, for which some implications are discussed.

Financial planning for major initiatives: a framework for success.

PubMed

Harris, John M

2007-11-01

A solid framework for assessing a major strategic initiative consists of four broad steps: Initial considerations, including level of analysis required and resources that will be brought to bear. Preliminary financial estimates for board approval to further assess the initiative. Assessment of potential partners' interest in the project. Feasibility analysis for board green light.

Developing tools to sustain biological diversity.

Treesearch

Randy Molina

2004-01-01

The Biodiversity Initiative strives to provide innovative solutions to the complex problem of managing forests for biodiversity. Although this initiative is in its beginning stages, an initial scoping meeting has already taken place and planning for the next steps is underway. The initiative is developing plans to conduct extensive scoping efforts in the management,...

Validity and reliability of the activPAL3 for measuring posture and stepping in adults and young people.

PubMed

Sellers, Ceri; Dall, Philippa; Grant, Margaret; Stansfield, Ben

2016-01-01

Characterisation of free-living physical activity requires the use of validated and reliable monitors. This study reports an evaluation of the validity and reliability of the activPAL3 monitor for the detection of posture and stepping in both adults and young people. Twenty adults (median 27.6y; IQR22.6y) and 8 young people (12.0y; IQR4.1y) performed standardised activities and activities of daily living (ADL) incorporating sedentary, upright and stepping activity. Agreement, specificity and positive predictive value were calculated between activPAL3 outcomes and the gold-standard of video observation. Inter-device reliability was calculated between 4 monitors. Sedentary and upright times for standardised activities were within ±5% of video observation as was step count (excluding jogging) for both adults and young people. Jogging step detection accuracy reduced with increasing cadence >150stepsmin(-1). For ADLs, sensitivity to stepping was very low for adults (40.4%) but higher for young people (76.1%). Inter-device reliability was either good (ICC(1,1)>0.75) or excellent (ICC(1,1)>0.90) for all outcomes. An excellent level of detection of standardised postures was demonstrated by the activPAL3. Postures such as seat-perching, kneeling and crouching were misclassified when compared to video observation. The activPAL3 appeared to accurately detect 'purposeful' stepping during ADL, but detection of smaller stepping movements was poor. Small variations in outcomes between monitors indicated that differences in monitor placement or hardware may affect outcomes. In general, the detection of posture and purposeful stepping with the activPAL3 was excellent indicating that it is a suitable monitor for characterising free-living posture and purposeful stepping activity in healthy adults and young people. Copyright © 2015 Elsevier B.V. All rights reserved.

Active Canada 20/20: A physical activity plan for Canada.

PubMed

Spence, John C; Faulkner, Guy; Costas Bradstreet, Christa; Duggan, Mary; Tremblay, Mark S

2016-03-16

Physical inactivity is a pressing public health concern. In this commentary we argue that Canada's approach to increasing physical activity (PA) has been fragmented and has lacked coordination, funding and a strategic approach. We then describe a potential solution in Active Canada 20/20 (AC 20/20), which provides both a national plan and a commitment to action from non-government and public sectors with a view to engaging corporate Canada and the general public. It outlines a road map for initiating, coordinating and implementing proactive initiatives to address this prominent health risk factor. The identified actions are based on the best available evidence and have been endorsed by the majority of representatives in the relevant sectors. The next crucial steps are to engage all those involved in public health promotion, service provision and advocacy at the municipal, provincial and national levels in order to incorporate AC 20/20 principles into practice and planning and thus increase the PA level of every person in Canada. Further, governments, as well as the private, not-for-profit and philanthropic sectors, should demonstrate leadership and continue their efforts toward providing the substantial and sustained resources needed to recalibrate Canadians' habitual PA patterns; this will ultimately improve the overall health of our citizens.

Activities Joining Learning Objectives to Assessments in Introductory Astronomy

NASA Astrophysics Data System (ADS)

Palen, Stacy E.; Larson, Ana M.

2015-01-01

In recent years, accreditation boards and other governing bodies have been pushing hard for explicit learning goals and quantitative measures of assessment for general education courses such as Astronomy 101. This added assessment burden can be problematic, especially for harried adjuncts teaching multiple courses at multiple institutions. It would be helpful to have a field-tested set of combined hands-on activities and assessment tools that help instructors meet these assessment requirements. The authors have produced just such a set. We have been using hands-on activities in our classrooms for more than 15 years. These activities require no special equipment or preparation and can be completed within an hour by most students working in groups of two or three. The sections of each activity are arranged in steps, guiding the students from initial knowledge-level questions or practice to a final evaluation or synthesis of what they have just accomplished. Students thus get practice thinking at higher cognitive levels. A recent addition to these activities is the inclusion of formalized learning objectives and accompanying pre- and post-activity questions. The pre-activity questions address common misconceptions, relate familiar analogous terrestrial examples to the activity, and act as a brief refresher meta-concepts like scale factors, measurements, and basic mathematics review. The post-activity questions review the most important concepts introduced in the activity. We present a number of examples as well as a summary as to how we have initiated their use in a large lecture setting of 300 students, in smaller classrooms of 15 students, and in a community college online course.

Virtual physiological human: training challenges.

PubMed

Lawford, Patricia V; Narracott, Andrew V; McCormack, Keith; Bisbal, Jesus; Martin, Carlos; Bijnens, Bart; Brook, Bindi; Zachariou, Margarita; Freixa, Jordi Villà I; Kohl, Peter; Fletcher, Katherine; Diaz-Zuccarini, Vanessa

2010-06-28

The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio.