Small-Molecule Inhibition and Activation-Loop Trans-Phosphorylation of the IGF1 Receptor

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

Wu,J.; Li, W.; Craddock, B.

2008-01-01

The insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase (RTK) that has a critical role in mitogenic signalling during embryogenesis and an antiapoptotic role in the survival and progression of many human tumours. Here, we present the crystal structure of the tyrosine kinase domain of IGF1R (IGF1RK), in its unphosphorylated state, in complex with a novel compound, cis-3-[3-(4-methyl-piperazin-l-yl)-cyclobutyl]-1-(2-phenyl-quinolin-7-yl)-imidazo[1, 5-a]pyrazin-8-ylamine (PQIP), which we show is a potent inhibitor of both the unphosphorylated (basal) and phosphorylated (activated) states of the kinase. PQIP interacts with residues in the ATP-binding pocket and in the activation loop, which confers specificity for IGF1RK andmore » the highly related insulin receptor (IR) kinase. In this crystal structure, the IGF1RK active site is occupied by Tyr1135 from the activation loop of an symmetry (two-fold)-related molecule. This dimeric arrangement affords, for the first time, a visualization of the initial trans-phosphorylation event in the activation loop of an RTK, and provides a molecular rationale for a naturally occurring mutation in the activation loop of the IR that causes type II diabetes mellitus.« less

Xrt And Shinx Joint Flare Study: Ar 11024

NASA Astrophysics Data System (ADS)

Engell, Alexander; Sylwester, J.; Siarkowski, M.

2010-05-01

From 12:00 UT on July 3 through July 7, 2009 SphinX (Solar Photometer IN X-rays) observes 130 flares with active region (AR) 11024 being the only AR on disk. XRT (X-Ray Telescope) is able to observe 64 of these flare events. The combination of both instruments results in a flare study revealing (1) a relationship between flux emergence and flare rate, (2) that the presence of active region loops typically results in different flare morphologies (single and multiple loop flares) then when there is a lack of an active region loop environment where more cusp and point-like flares are observed, (3) cusp and point-like flares often originate from the same location, and (4) a distribution of flare temperatures corresponding to the different flare morphologies. The differences between the observed flare morphologies may occur as the result of the heated plasma through the flaring process being confined by the proximity of loop structures as for the single and multiple loop flares, while for cusp and point-like flares they occur in an early-phase environment that lack loop presence. The continuing flux emergence of AR 11024 likely provides different magnetic interactions and may be the source responsible for all of the flares.

Flares observed by the normal incidence X-ray telescope on 1989 September 11

NASA Technical Reports Server (NTRS)

Herant, M.; Pardo, F.; Spiller, E.; Golub, L.

1991-01-01

Two solar flare events have been observed in soft X-rays during a sounding-rocket flight of the Normal-Incidence X-ray Telescope payload on September 11, 1989. The flare in X-rays involves a single bright loop crossing the neutral line, and having its footpoints at the southern ends of the ribbons; this loop accounts for more than 66 percent of the emission. Within the remainder of each of the flare ribbons, a complex coronal structure is also observed to be interacting with the main flare loop. A second event, in an active region at the limb, has a strong correlation with H-alpha images obtained at the same time. This indicates the coexistence, and indeed the close proximity, of coronal and chromospheric temperature material. Interpretations of this phenomenon are discussed.

Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations. A cost-effectiveness analysis

NASA Technical Reports Server (NTRS)

Zimetbaum, P. J.; Kim, K. Y.; Josephson, M. E.; Goldberger, A. L.; Cohen, D. J.

1998-01-01

BACKGROUND: Continuous-loop event recorders are widely used for the evaluation of palpitations, but the optimal duration of monitoring is unknown. OBJECTIVE: To determine the yield, timing, and incremental cost-effectiveness of each week of event monitoring for palpitations. DESIGN: Prospective cohort study. PATIENTS: 105 consecutive outpatients referred for the placement of a continuous-loop event recorder for the evaluation of palpitations. MEASUREMENTS: Diagnostic yield, incremental cost, and cost-effectiveness for each week of monitoring. RESULTS: The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per patient in week 3 and beyond. Over time, the cost-effectiveness ratio increased from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and $5832 per new diagnosis in week 3. CONCLUSIONS: In patients referred for evaluation of palpitations, the diagnostic yield of continuous-loop event recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring period is reasonably cost-effective for most patients and should be the standard period for continuous-loop event recording for the evaluation of palpitations.

Cool Transition Region Loops Observed by the Interface Region Imaging Spectrograph

NASA Astrophysics Data System (ADS)

Huang, Zhenghua; Xia, Lidong; Li, Bo; Madjarska, Maria S.

2015-09-01

We report on the first Interface Region Imaging Spectrograph (IRIS) study of cool transition region loops, a class of loops that has received little attention in the literature. A cluster of such loops was observed on the solar disk in active region NOAA11934, in the Si iv 1402.8 Å spectral raster and 1400 Å slit-jaw images. We divide the loops into three groups and study their dynamics. The first group comprises relatively stable loops, with 382-626 km cross-sections. Observed Doppler velocities are suggestive of siphon flows, gradually changing from -10 km s-1 at one end to 20 km s-1 at the other end of the loops. Nonthermal velocities of 15 ˜ 25 km s-1 were determined. Magnetic cancellation with a rate of 1015 Mx s-1 is found at the blueshifted footpoints. These physical properties suggest that these loops are impulsively heated by magnetic reconnection, and the siphon flows play an important role in the energy redistribution. The second group corresponds to two footpoints rooted in mixed-magnetic-polarity regions, where magnetic cancellation with a rate of 1015 Mx s-1 and explosive-event line profiles with enhanced wings of up to 200 km s-1 were observed. In the third group, interaction between two cool loop systems is observed. Evidence for magnetic reconnection between the two loop systems is reflected in the explosive-event line profiles and magnetic cancellation with a rate of 3× {10}15 Mx s-1 observed in the corresponding area. The IRIS has provided opportunity for in-depth investigations of cool transition region loops. Further numerical experiments are crucial for understanding their physics and their roles in the coronal heating processes.

Analysis of Loss-of-Offsite-Power Events 1997-2015

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

Johnson, Nancy Ellen; Schroeder, John Alton

2016-07-01

Loss of offsite power (LOOP) can have a major negative impact on a power plant’s ability to achieve and maintain safe shutdown conditions. LOOP event frequencies and times required for subsequent restoration of offsite power are important inputs to plant probabilistic risk assessments. This report presents a statistical and engineering analysis of LOOP frequencies and durations at U.S. commercial nuclear power plants. The data used in this study are based on the operating experience during calendar years 1997 through 2015. LOOP events during critical operation that do not result in a reactor trip, are not included. Frequencies and durations weremore » determined for four event categories: plant-centered, switchyard-centered, grid-related, and weather-related. Emergency diesel generator reliability is also considered (failure to start, failure to load and run, and failure to run more than 1 hour). There is an adverse trend in LOOP durations. The previously reported adverse trend in LOOP frequency was not statistically significant for 2006-2015. Grid-related LOOPs happen predominantly in the summer. Switchyard-centered LOOPs happen predominantly in winter and spring. Plant-centered and weather-related LOOPs do not show statistically significant seasonality. The engineering analysis of LOOP data shows that human errors have been much less frequent since 1997 than in the 1986 -1996 time period.« less

A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

NASA Astrophysics Data System (ADS)

Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

2013-11-01

Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

On Heating the Sun's Corona by Magnetic Explosions: Feasibility in Active Regions and prospects for Quiet Regions and Coronal Holes

NASA Technical Reports Server (NTRS)

Moore, Ronald L.; Falconer, D. A.; Porter, Jason G.; Suess, Steven T.

1999-01-01

We build a case for the persistent strong coronal heating in active regions and the pervasive quasi-steady heating of the corona in quiet regions and coronal holes being driven in basically the same way as the intense transient heating in solar flares: by explosions of sheared magnetic fields in the cores of initially closed bipoles. We begin by summarizing the observational case for exploding sheared core fields being the drivers of a wide variety of flare events, with and without coronal mass ejections. We conclude that the arrangement of an event's flare heating, whether there is a coronal mass ejection, and the time and place of the ejection relative to the flare heating are all largely determined by four elements of the form and action of the magnetic field: (1) the arrangement of the impacted, interacting bipoles participating in the event, (2) which of these bipoles are active (have sheared core fields that explode) and which are passive (are heated by injection from impacted active bipoles), (3) which core field explodes first, and (4) which core-field explosions are confined within the closed field of their bipoles and which ejectively open their bipoles. We then apply this magnetic-configuration framework for flare heating to the strong coronal heating observed by the Yohkoh Soft X-ray Telescope in an active region with strongly sheared core fields observed by the MSFC vector magnetograph. All of the strong coronal heating is in continually microflaring sheared core fields or in extended loops rooted against the active core fields. Thus, the strong heating occurs in field configurations consistent with the heating being driven by frequent core-field explosions that are smaller but similar to those in confined flares and flaring arches. From analysis of the thermal and magnetic energetics of two selected core-field microflares and a bright extended loop, we find that (1) it is energetically feasible for the sheared core fields to drive all of the coronal heating in the active region via a staccato of magnetic microexplosions, (2) the microflares at the feet of the extended loop behave as the flares at the feet of flaring arches in that more coronal heating is driven within the active bipole than in the extended loop, (3) the filling factor of the X-ray plasma in the core field microflares and in the extended loop is approximately 0.1, and (4) to release enough magnetic energy for a typical microflare (10^27 - 10^28 erg), a microflaring strand of sheared core field need expand and/or untwist by only a few percent at most. Finally, we point out that (1) the field configurations for strong coronal heating in our example active region (i.e., neutral-line core fields, many embedded in the feet of extended loops) are present in abundance in the magnetic network in quiet regions and coronal holes, and (2) it is known that many network bipoles do microflare and that many produce detectable coronal heating. We therefore propose that exploding sheared core fields are the drivers of most of the heating and dynamics of the solar atmosphere, ranging from the largest and most powerful coronal mass ejections and flares, to the vigorous microflaring and coronal heating in active regions, to the multitude of fine-scale explosive events in the magnetic network. The low-lysing exploding core fields in the network drive microflares, spicules, global coronal heating, and ,consequently, the solar wind.

THE COLD SHOULDER: EMISSION MEASURE DISTRIBUTIONS OF ACTIVE REGION CORES

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

Schmelz, J. T.; Pathak, S., E-mail: jschmelz@memphis.edu

2012-09-10

The coronal heating mechanism for active region core loops is difficult to determine because these loops are often not resolved and cannot be studied individually. Rather, we concentrate on the 'inter-moss' areas between loop footpoints. We use observations from the Hinode EUV Imaging Spectrometer and the X-Ray Telescope to calculate the emission measure distributions of eight inter-moss areas in five different active regions. The combined data sets provide both high- and low-temperature constraints and ensure complete coverage in the temperature range appropriate for active regions. For AR 11113, the emission can be modeled with heating events that occur on timescalesmore » less than the cooling time. The loops in the core regions appear to be close to equilibrium and are consistent with steady heating. The other regions studied, however, appear to be dominated by nanoflare heating. Our results are consistent with the idea that active region age is an important parameter in determining whether steady or nanoflare heating is primarily responsible for the core emission, that is, older regions are more likely to be dominated by steady heating, while younger regions show more evidence of nanoflares.« less

Severe Weather and Special Events - NOAA GOES Geostationary Satellite

Science.gov Websites

IR Image Loop Infrared 2 Event 4 Chan 2 Image Visible Event 4 VIS Image Loop Water Vapor Event 4 WV ;. This web site should not be used to support operational observation, forecasting, emergency, or

The sun's spots and flares

NASA Technical Reports Server (NTRS)

Rust, David M.

1987-01-01

The Solar Maximum Mission (SMM), designed to study the solar activity, was launched on February 14, 1980, just before the 1980 peak of sunspot and flare activity. The seven instruments aboard the SMM, information received by each of the instruments, and the performance of these instruments are described, together with the repair mission carried out to replace the attitude control module and the defective electronics in the satellite's observatory. The highlights of the scientific results obtained by the SMM mission and the new discoveries made are discussed, with special attention given to the flare loops, flare loop interactions, and the mass ejection events recorded.

Big words, halved brains and small worlds: complex brain networks of figurative language comprehension.

PubMed

Arzouan, Yossi; Solomon, Sorin; Faust, Miriam; Goldstein, Abraham

2011-04-27

Language comprehension is a complex task that involves a wide network of brain regions. We used topological measures to qualify and quantify the functional connectivity of the networks used under various comprehension conditions. To that aim we developed a technique to represent functional networks based on EEG recordings, taking advantage of their excellent time resolution in order to capture the fast processes that occur during language comprehension. Networks were created by searching for a specific causal relation between areas, the negative feedback loop, which is ubiquitous in many systems. This method is a simple way to construct directed graphs using event-related activity, which can then be analyzed topologically. Brain activity was recorded while subjects read expressions of various types and indicated whether they found them meaningful. Slightly different functional networks were obtained for event-related activity evoked by each expression type. The differences reflect the special contribution of specific regions in each condition and the balance of hemispheric activity involved in comprehending different types of expressions and are consistent with the literature in the field. Our results indicate that representing event-related brain activity as a network using a simple temporal relation, such as the negative feedback loop, to indicate directional connectivity is a viable option for investigation which also derives new information about aspects not reflected in the classical methods for investigating brain activity.

A white-light /Fe X/H-alpha coronal transient observation to 10 solar radii

NASA Technical Reports Server (NTRS)

Wagner, W. J.; Illing, R. M. E.; Sawyer, C. B.; House, L. L.; Sheeley, N. R., Jr.; Howard, R. A.; Koomen, M. J.; Michels, D. J.; Smartt, R. N.; Dryer, M.

1983-01-01

Multitelescope observations of the coronal transient of April 15-16, 1980 provide simultaneous data from the Solar Maximum Mission Coronagraph/Polarimeter, the Solwind Coronagraph, and the new Emission line Coronagraph of the Sacramento Peak Observatory. An eruptive prominence-associated white light transient is for the first time seen as an unusual wave or brightening in Fe X 6374 A (but not in Fe XIV 5303 A). Several interpretations of this fleeting enhancement are offered. The prominence shows a slowly increasing acceleration which peaks at the time of the Fe event. The white light loop transient surrounding the prominence expands at a well-documented constant speed to solar radii, with an extrapolated start time at zero height coincident with the surface activity. This loop transient exemplifies those seen above 1.7 solar radii, in that leading the disturbance is a bright N(e)-enhanced) loop rather than a dark one. This is consistent with a report of the behavior of another eruptive event observed by Fisher and Poland (1981) which began as a density depletion in the lower corona, with a bright loop forming at greater altitudes. The top of the bright loop ultimately fades in the outer corona while slow radial growth continues in the legs.

The location of the site of energy release in a solar X-ray subflare

NASA Technical Reports Server (NTRS)

Petrasso, R. D.; Kahler, S. W.; Krieger, A. S.; Silk, J. K.; Vaiana, G. S.

1975-01-01

A rapid sequence of high-resolution X-ray photographs was obtained by the S-054 X-ray Telescope Experiment on Skylab on 1973 September 1. During the course of this observation, photographs were obtained of a flarelike brightening in a simple, bipolar active region. Analysis reveals the following facts. The event had the form of a small, elongated bright feature whose narrowest dimension was less than seconds of arc. The brightness peak of the flarelike brightening was located within seconds of arc of the center of brightness of a preexisting loop structure that crossed the magnetic neutral line. This loop was observed to brighten gradually beginning approximately 10 minutes prior to the flarelike event. During the rise of the event, the 2-17 A X-ray brightness of the center of the subflare core rose by over a factor of 10 in a time period of 196 seconds or less.

An Assessment of Magnetic Conditions for Strong Coronal Heating in Solar Active Regions by Comparing Observed Loops with Computed Potential Field Lines

NASA Technical Reports Server (NTRS)

Gary, G. A.; Moore, R. L.; Porter, J. G.; Falconer, D. A.

1999-01-01

We report further results on the magnetic origins of coronal heating found from registering coronal images with photospheric vector magnetograms. For two complementary active regions, we use computed potential field lines to examine the global non-potentiality of bright extended coronal loops and the three-dimensional structure of the magnetic field at their feet, and assess the role of these magnetic conditions in the strong coronal heating in these loops. The two active regions are complementary, in that one is globally potential and the other is globally nonpotential, while each is predominantly bipolar, and each has an island of included polarity in its trailing polarity domain. We find the following: (1) The brightest main-arch loops of the globally potential active region are brighter than the brightest main- arch loops of the globally strongly nonpotential active region. (2) In each active region, only a few of the mainarch magnetic loops are strongly heated, and these are all rooted near the island. (3) The end of each main-arch bright loop apparently bifurcates above the island, so that it embraces the island and the magnetic null above the island. (4) At any one time, there are other main-arch magnetic loops that embrace the island in the same manner as do the bright loops but that are not selected for strong coronal heating. (5) There is continual microflaring in sheared core fields around the island, but the main-arch bright loops show little response to these microflares. From these observational and modeling results we draw the following conclusions: (1) The heating of the main-arch bright loops arises mainly from conditions at the island end of these loops and not from their global non-potentiality. (2) There is, at most, only a loose coupling between the coronal heating in the bright loops of the main arch and the coronal heating in the sheared core fields at their feet, although in both the heating is driven by conditions/events in and around the island. (3) The main-arch bright loops are likely to be heated via reconnection driven at the magnetic null over the island. The details of how and where (along the null line) the reconnection is driven determine which of the split-end loops are selected for strong heating. (4) The null does not appear to be directly involved in the heating of the sheared core fields or in the heating of an extended loop rooted in the island. Rather, these all appear to be heated by microflares in the sheared core field.

Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling

PubMed Central

Lareo, Angel; Forlim, Caroline G.; Pinto, Reynaldo D.; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox. PMID:27766078

Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling.

PubMed

Lareo, Angel; Forlim, Caroline G; Pinto, Reynaldo D; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox.

Phosphorylation of the Activation Loop Tyrosine 823 in c-Kit Is Crucial for Cell Survival and Proliferation*

PubMed Central

Agarwal, Shruti; Kazi, Julhash U.; Rönnstrand, Lars

2013-01-01

The receptor tyrosine kinase c-Kit, also known as the stem cell factor receptor, plays a key role in several developmental processes. Activating mutations in c-Kit lead to alteration of these cellular processes and have been implicated in many human cancers such as gastrointestinal stromal tumors, acute myeloid leukemia, testicular seminomas and mastocytosis. Regulation of the catalytic activity of several kinases is known to be governed by phosphorylation of tyrosine residues in the activation loop of the kinase domain. However, in the case of c-Kit phosphorylation of Tyr-823 has been demonstrated to be a late event that is not required for kinase activation. However, because phosphorylation of Tyr-823 is a ligand-activated event, we sought to investigate the functional consequences of Tyr-823 phosphorylation. By using a tyrosine-to-phenylalanine mutant of tyrosine 823, we investigated the impact of Tyr-823 on c-Kit signaling. We demonstrate here that Tyr-823 is crucial for cell survival and proliferation and that mutation of Tyr-823 to phenylalanine leads to decreased sustained phosphorylation and ubiquitination of c-Kit as compared with the wild-type receptor. Furthermore, the mutated receptor was, upon ligand-stimulation, quickly internalized and degraded. Phosphorylation of the E3 ubiquitin ligase Cbl was transient, followed by a substantial reduction in phosphorylation of downstream signaling molecules such as Akt, Erk, p38, Shc, and Gab2. Thus, we propose that activation loop tyrosine 823 is crucial for activation of both the MAPK and PI3K pathways and that its disruption leads to a destabilization of the c-Kit receptor and decreased survival of cells. PMID:23803604

Multiple roles of mobile active center loops in the E1 component of the Escherichia coli pyruvate dehydrogenase complex - Linkage of protein dynamics to catalysis

PubMed Central

Jordan, Frank; Arjunan, Palaniappa; Kale, Sachin; Nemeria, Natalia S.; Furey, William

2009-01-01

The region encompassing residues 401–413 on the E1 component of the pyruvate dehydrogenase multienzyme complex from Escherichia coli comprises a loop (the inner loop) which was not seen in the X-ray structure in the presence of thiamin diphosphate, the required cofactor for the enzyme. This loop is seen in the presence of a stable analogue of the pre-decarboxylation intermediate, the covalent adduct between the substrate analogue methyl acetylphosphonate and thiamin diphosphate, C2α-phosphonolactylthiamin diphosphate. It has been shown that the residue H407 and several other residues on this loop are required to reduce the mobility of the loop so electron density corresponding to it can be seen once the pre-decarboxylation intermediate is formed. Concomitantly, the loop encompassing residues 541–557 (the outer loop) appears to work in tandem with the inner loop and there is a hydrogen bond between the two loops ensuring their correlated motion. The inner loop was shown to: a) sequester the active center from carboligase side reactions; b) assist the interaction between the E1 and the E2 components, thereby affecting the overall reaction rate of the entire multienzyme complex; c) control substrate access to the active center. Using viscosity effects on kinetics it was shown that formation of the pre-decarboxylation intermediate is specifically affected by loop movement. A cysteine-less variant was created for the E1 component, onto which cysteines were substituted at selected loop positions. Introducing an electron spin resonance spin label and an 19F NMR label onto these engineered cysteines, the loop mobility was examined: a) both methods suggested that in the absence of ligand, the loop exists in two conformations; b) line-shape analysis of the NMR signal at different temperatures, enabled estimation of the rate constant for loop movement, and this rate constant was found to be of the same order of magnitude as the turnover number for the enzyme under the same conditions. Furthermore, this analysis gave important insights into rate-limiting thermal loop dynamics. Overall, the results suggest that the dynamic properties correlate with catalytic events on the E1 component of the pyruvate dehydrogenase complex. PMID:20160956

The January 2015 Repressurization of ISS ATCS Loop B - Analysis Limitations and Concerns

NASA Technical Reports Server (NTRS)

Ungar, Eugene; Rankin, J. Gary; Schaff, Mary; Figueroa, Marcelino

2015-01-01

In January 2013 a false ammonia leak alarm resulted in the shutdown and partial depressurization of one of the two International Space Station (ISS) External Active Thermal Control System (EATCS) loops. The depressurization resulted in a vapor bubble of 18 liters in warm parts of the stagnant loop. To repressurize the loop and regain system operation, liquid would have to be moved from the Ammonia Tank Assembly (ATA) into the loop. This resulted in the possibility of moving cold (as low as -30 C) ammonia into the water-filled Internal Active Thermal Control System (IATCS) interface heat exchangers. Before moving forward, the freezing potential of the repressurization was evaluated through analysis - using both a Thermal Desktop SINDA/FLUINT model and hand calculations. The models yielded very different results, but both models indicated that heat exchanger freezing was not an issue. Therefore, the repressurization proceeded. The presentation describes the physical situation of the EATCS prior to repressurization and discusses the potential limits and pitfalls of the repressurization. The pre-repressurization analytical models and their results are discussed. The successful repressurization is describled and the results of a post-event model assessment is detailed.

An α-subunit loop structure is required for GM2 activator protein binding by β-hexosaminidase A

PubMed Central

Zarghooni, Maryam; Bukovac, Scott; Tropak, Michael; Callahan, John; Mahuran, Don

2010-01-01

The α- and/or β-subunits of human β-hexosaminidase A (αβ) and B (ββ) are ~60% identical. In vivo only β-hexosaminidase A can utilize GM2 ganglioside as a substrate, but requires the GM2 activator protein to bind GM2 ganglioside and then interact with the enzyme, placing the terminal GalNAc residue in the active site of the α-subunit. A model for this interaction suggests that two loop structures, present only in the α-subunit, may be critical to this binding. Three amino acids in one of these loops are not encoded in the HEXB gene, while four from the other are removed posttranslationally from the pro-β-subunit. Natural substrate assays with forms of hexosaminidase A containing mutant α-subunits demonstrate that only the site that is removed from the β-subunit during its maturation is critical for the interaction. Our data suggest an unexpected biological role for such proteolytic processing events. PMID:15485660

NEW ASPECTS OF A LID-REMOVAL MECHANISM IN THE ONSET OF AN ERUPTION SEQUENCE THAT PRODUCED A LARGE SOLAR ENERGETIC PARTICLE (SEP) EVENT

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

Sterling, Alphonse C.; Moore, Ronald L.; Falconer, David A.

We examine a sequence of two ejective eruptions from a single active region on 2012 January 23, using magnetograms and EUV images from the Solar Dynamics Observatory's (SDO) Helioseismic and Magnetic Imager (HMI) and Atmospheric and Imaging Assembly (AIA), and EUV images from STEREO/EUVI. This sequence produced two coronal mass ejections (CMEs) and a strong solar energetic particle event (SEP); here we focus on the magnetic onset of this important space weather episode. Cheng et al. showed that the first eruption's ({sup E}ruption 1{sup )} flux rope was apparent only in ''hotter'' AIA channels, and that it removed overlying field thatmore » allowed the second eruption ({sup E}ruption 2{sup )} to begin via ideal MHD instability; here we say that Eruption 2 began via a ''lid removal'' mechanism. We show that during Eruption 1's onset, its flux rope underwent a ''tether weakening'' (TW) reconnection with field that arched from the eruption-source active region to an adjacent active region. Standard flare loops from Eruption 1 developed over Eruption 2's flux rope and enclosed filament, but these overarching new loops were unable to confine that flux rope/filament. Eruption 1's flare loops, from both TW reconnection and standard-flare-model internal reconnection, were much cooler than Eruption 2's flare loops (GOES thermal temperatures of ∼7.5 MK and 9 MK, compared to ∼14 MK). The corresponding three sequential GOES flares were, respectively, due to TW reconnection plus earlier phase Eruption 1 tether-cutting reconnection, Eruption 1 later-phase tether-cutting reconnection, and Eruption 2 tether-cutting reconnection.« less

Automated event generation for loop-induced processes

DOE PAGES

Hirschi, Valentin; Mattelaer, Olivier

2015-10-22

We present the first fully automated implementation of cross-section computation and event generation for loop-induced processes. This work is integrated in the MadGraph5_aMC@NLO framework. We describe the optimisations implemented at the level of the matrix element evaluation, phase space integration and event generation allowing for the simulation of large multiplicity loop-induced processes. Along with some selected differential observables, we illustrate our results with a table showing inclusive cross-sections for all loop-induced hadronic scattering processes with up to three final states in the SM as well as for some relevant 2 → 4 processes. Furthermore, many of these are computed heremore » for the first time.« less

The Heating of Solar Coronal Loops by Alfvén Wave Turbulence

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

Van Ballegooijen, A. A.; Asgari-Targhi, M.; Voss, A.

2017-11-01

In this paper we further develop a model for the heating of coronal loops by Alfvén wave turbulence (AWT). The Alfvén waves are assumed to be launched from a collection of kilogauss flux tubes in the photosphere at the two ends of the loop. Using a three-dimensional magnetohydrodynamic model for an active-region loop, we investigate how the waves from neighboring flux tubes interact in the chromosphere and corona. For a particular combination of model parameters we find that AWT can produce enough heat to maintain a peak temperature of about 2.5 MK, somewhat lower than the temperatures of 3–4 MKmore » observed in the cores of active regions. The heating rates vary strongly in space and time, but the simulated heating events have durations less than 1 minute and are unlikely to reproduce the observed broad differential emission measure distributions of active regions. The simulated spectral line nonthermal widths are predicted to be about 27 km s{sup −1}, which is high compared to the observed values. Therefore, the present AWT model does not satisfy the observational constraints. An alternative “magnetic braiding” model is considered in which the coronal field lines are subject to slow random footpoint motions, but we find that such long-period motions produce much less heating than the shorter-period waves launched within the flux tubes. We discuss several possibilities for resolving the problem of producing sufficiently hot loops in active regions.« less

Intermittent muscle activity in the feedback loop of postural control system during natural quiet standing.

PubMed

Tanabe, Hiroko; Fujii, Keisuke; Kouzaki, Motoki

2017-09-06

The origin of continual body oscillation during quiet standing is a neural-muscular-skeletal closed feedback loop system that includes insufficient joint stiffness and a time delay. Thus, muscle activity and joint oscillations are nonlinear during quiet standing, making it difficult to demonstrate the muscular-skeletal relationship experimentally. Here we experimentally revealed this relationship using intermittent control theory, in which non-actuation works to stabilize the skeletal system towards equilibrium. We found that leg muscles were activated/inactivated when the state point was located in the opposite/same direction as the direction of anatomical action, which was associated with joint torque actuating the body towards equilibrium. The derivative values of stability index defined in the phase space approximately 200 ms before muscle inactivation were also larger than those before activation for some muscles. These results indicate that bipedal standing might be achieved by monitoring the rate of change of stability/instability components and generating joint torque to stabilize the body. In conclusion, muscles are likely to activate in an event-driven manner during quiet standing and a possible metric for on/off switching is SI dot, and our methodology of EMG processing could allows us to extract such event-driven intermittent muscle activities.

OBSERVING CORONAL NANOFLARES IN ACTIVE REGION MOSS

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

Testa, Paola; DeLuca, Ed; Golub, Leon

2013-06-10

The High-resolution Coronal Imager (Hi-C) has provided Fe XII 193A images of the upper transition region moss at an unprecedented spatial ({approx}0.''3-0.''4) and temporal (5.5 s) resolution. The Hi-C observations show in some moss regions variability on timescales down to {approx}15 s, significantly shorter than the minute-scale variability typically found in previous observations of moss, therefore challenging the conclusion of moss being heated in a mostly steady manner. These rapid variability moss regions are located at the footpoints of bright hot coronal loops observed by the Solar Dynamics Observatory/Atmospheric Imaging Assembly in the 94 A channel, and by the Hinode/X-Raymore » Telescope. The configuration of these loops is highly dynamic, and suggestive of slipping reconnection. We interpret these events as signatures of heating events associated with reconnection occurring in the overlying hot coronal loops, i.e., coronal nanoflares. We estimate the order of magnitude of the energy in these events to be of at least a few 10{sup 23} erg, also supporting the nanoflare scenario. These Hi-C observations suggest that future observations at comparable high spatial and temporal resolution, with more extensive temperature coverage, are required to determine the exact characteristics of the heating mechanism(s).« less

Interactive flare sites within an active region complex

NASA Technical Reports Server (NTRS)

Poletto, G.; Gary, G. A.; Machado, M. E.

1993-01-01

We examine here a set of images of an active region complex, acquired on June 24-25, 1980, by the Hard X-ray Imaging Spectrometer on SMM, with the purpose of establishing whether there was any interplay between the frequent activity observed at different sites in the activity center and, in such a case, how the interaction was established. By analyzing both quiet and active orbits we show that, as a rule, activity originating in one region triggers the other region's activity. However, we find little unambiguous evidence for the presence of large-scale interconnecting loops. A comparison of X-ray images with magnetic field observations suggested that we interpret the active region behavior in terms of the interaction between different loop systems, in a scenario quite analogous to the interacting bipole representation of individual flares. We conclude that active region interplay provides an easily observable case to study the time-dependent topology and the mechanisms for the spreading of activity in transient events over all energy scales.

78 FR 19155 - Special Local Regulations; Marine Events, Wrightsville Channel; Wrightsville Beach, NC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-29

... establish a Special Local Regulation for the ``Swim the Loop/Motts Channel Sprint'' swim event, to be held..., mile 283.1, at Wrightsville Beach, North Carolina, during the swim event. DATES: Comments and related...:45 a.m., Without Limits Coaching will sponsor ``Swim the Loop'' and the ``Motts Channel Sprint'' on...

Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops.

PubMed

Zuchegna, Candida; Aceto, Fabiana; Bertoni, Alessandra; Romano, Antonella; Perillo, Bruno; Laccetti, Paolo; Gottesman, Max E; Avvedimento, Enrico V; Porcellini, Antonio

2014-01-01

Histone methylation changes and formation of chromatin loops involving enhancers, promoters and 3' end regions of genes have been variously associated with active transcription in eukaryotes. We have studied the effect of activation of the retinoic A receptor, at the RARE-promoter chromatin of CASP9 and CYP26A1 genes, 15 and 45 min following RA exposure, and we found that histone H3 lysines 4 and 9 are demethylated by the lysine-specific demethylase, LSD1 and by the JMJ-domain containing demethylase, D2A. The action of the oxidase (LSD1) and a dioxygenase (JMJD2A) in the presence of Fe++ elicits an oxidation wave that locally modifies the DNA and recruits the enzymes involved in base and nucleotide excision repair (BER and NER). These events are essential for the formation of chromatin loop(s) that juxtapose the RARE element with the 5' transcription start site and the 3' end of the genes. The RARE bound-receptor governs the 5' and 3' end selection and directs the productive transcription cycle of RNA polymerase. These data mechanistically link chromatin loops, histone methylation changes and localized DNA repair with transcription. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structures far from the head of comet Kohoutek. II - A discussion of the Swan Cloud of January 11 and of the general morphology of cometary plasma tails

NASA Technical Reports Server (NTRS)

Niedner, M. B., Jr.; Brandt, J. C.

1980-01-01

Photographs show that the 'Swan Cloud' observed in comet Kohoutek on January 11, 1974 was an advanced stage of a plasma tail disconnection event, of which the rejected tail appeared to decelerate as it receded from the head. The event commenced with the development of strong tail ray activity followed by the actual tail disconnection, the merging of the disconnected tail with the new tail to form the Swan and the formation of arcade loops in the space between closing tail rays. The observed morphological sequence is easily understood in the sector boundary model (Niedner et al., 1978), and the arcade loops are proposed to be reconnected flux tubes between oppositely polarized tail rays in the incipient new tail which followed the disconnection

Simplifying operations with an uplink/downlink integration toolkit

NASA Technical Reports Server (NTRS)

Murphy, Susan C.; Miller, Kevin J.; Guerrero, Ana Maria; Joe, Chester; Louie, John J.; Aguilera, Christine

1994-01-01

The Operations Engineering Lab (OEL) at JPL has developed a simple, generic toolkit to integrate the uplink/downlink processes, (often called closing the loop), in JPL's Multimission Ground Data System. This toolkit provides capabilities for integrating telemetry verification points with predicted spacecraft commands and ground events in the Mission Sequence Of Events (SOE) document. In the JPL ground data system, the uplink processing functions and the downlink processing functions are separate subsystems that are not well integrated because of the nature of planetary missions with large one-way light times for spacecraft-to-ground communication. Our new closed-loop monitoring tool allows an analyst or mission controller to view and save uplink commands and ground events with their corresponding downlinked telemetry values regardless of the delay in downlink telemetry and without requiring real-time intervention by the user. An SOE document is a time-ordered list of all the planned ground and spacecraft events, including all commands, sequence loads, ground events, significant mission activities, spacecraft status, and resource allocations. The SOE document is generated by expansion and integration of spacecraft sequence files, ground station allocations, navigation files, and other ground event files. This SOE generation process has been automated within the OEL and includes a graphical, object-oriented SOE editor and real-time viewing tool running under X/Motif. The SOE toolkit was used as the framework for the integrated implementation. The SOE is used by flight engineers to coordinate their operations tasks, serving as a predict data set in ground operations and mission control. The closed-loop SOE toolkit allows simple, automated integration of predicted uplink events with correlated telemetry points in a single SOE document for on-screen viewing and archiving. It automatically interfaces with existing real-time or non real-time sources of information, to display actual values from the telemetry data stream. This toolkit was designed to greatly simplify the user's ability to access and view telemetry data, and also provide a means to view this data in the context of the commands and ground events that are used to interpret it. A closed-loop system can prove especially useful in small missions with limited resources requiring automated monitoring tools. This paper will discuss the toolkit implementation, including design trade-offs and future plans for enhancing the automated capabilities.

Simplifying operations with an uplink/downlink integration toolkit

NASA Astrophysics Data System (ADS)

Murphy, Susan C.; Miller, Kevin J.; Guerrero, Ana Maria; Joe, Chester; Louie, John J.; Aguilera, Christine

1994-11-01

The Operations Engineering Lab (OEL) at JPL has developed a simple, generic toolkit to integrate the uplink/downlink processes, (often called closing the loop), in JPL's Multimission Ground Data System. This toolkit provides capabilities for integrating telemetry verification points with predicted spacecraft commands and ground events in the Mission Sequence Of Events (SOE) document. In the JPL ground data system, the uplink processing functions and the downlink processing functions are separate subsystems that are not well integrated because of the nature of planetary missions with large one-way light times for spacecraft-to-ground communication. Our new closed-loop monitoring tool allows an analyst or mission controller to view and save uplink commands and ground events with their corresponding downlinked telemetry values regardless of the delay in downlink telemetry and without requiring real-time intervention by the user. An SOE document is a time-ordered list of all the planned ground and spacecraft events, including all commands, sequence loads, ground events, significant mission activities, spacecraft status, and resource allocations. The SOE document is generated by expansion and integration of spacecraft sequence files, ground station allocations, navigation files, and other ground event files. This SOE generation process has been automated within the OEL and includes a graphical, object-oriented SOE editor and real-time viewing tool running under X/Motif. The SOE toolkit was used as the framework for the integrated implementation. The SOE is used by flight engineers to coordinate their operations tasks, serving as a predict data set in ground operations and mission control. The closed-loop SOE toolkit allows simple, automated integration of predicted uplink events with correlated telemetry points in a single SOE document for on-screen viewing and archiving. It automatically interfaces with existing real-time or non real-time sources of information, to display actual values from the telemetry data stream. This toolkit was designed to greatly simplify the user's ability to access and view telemetry data, and also provide a means to view this data in the context of the commands and ground events that are used to interpret it. A closed-loop system can prove especially useful in small missions with limited resources requiring automated monitoring tools. This paper will discuss the toolkit implementation, including design trade-offs and future plans for enhancing the automated capabilities.

Combined deficiency of MSH2 and Sμ region abolishes class switch recombination.

PubMed

Leduc, Claire; Haddad, Dania; Laviolette-Malirat, Nathalie; Nguyen Huu, Ngoc-Sa; Khamlichi, Ahmed Amine

2010-10-01

Class switch recombination (CSR) is mediated by G-rich tandem repeated sequences termed switch regions. Transcription of switch regions generates single-stranded R loops that provide substrates for activation-induced cytidine deaminase. Mice deficient in MSH2 have a mild defect in CSR and analysis of their switch junctions has led to a model in which MSH2 is more critical for switch recombination events outside than within the tandem repeats. It is also known that deletion of the whole Sμ region severely impairs but does not abrogate CSR despite the lack of detectable R loops. Here, we demonstrate that deficiency of both MSH2 and the Sμ region completely abolishes CSR and that the abrogation occurs at the genomic level. This finding further supports the crucial role of MSH2 outside the tandem repeats. It also indicates that during CSR, MSH2 has access to activation-induced cytidine deaminase targets in R-loop-deficient Iμ-Cμ sequences rarely used in CSR, suggesting an MSH2-dependent DNA processing activity at the Iμ exon that may decrease with transcription elongation across the Sμ region.

The use of external event monitoring (web-loop) in the elucidation of symptoms associated with arrhythmias in a general population

PubMed Central

Epifanio, Hindalis Ballesteros; Katz, Marcelo; Borges, Melania Aparecida; Corrêa, Alessandra da Graça; Cintra, Fátima Dumas; Grinberg, Rodrigo Leandro; Ludovice, Ana Cristina Pinotti Pedro; Valdigem, Bruno Pereira; da Silva, Nilton José Carneiro; Fenelon, Guilherme

2014-01-01

Objective To correlate arrhythmic symptoms with the presence of significant arrhythmias through the external event monitoring (web-loop). Methods Between January and December 2011, the web-loop was connected to 112 patients (46% of them were women, mean age 52±21 years old). Specific arrhythmic symptoms were defined as palpitations, pre-syncope and syncope observed during the monitoring. Supraventricular tachycardia, atrial flutter or fibrillation, ventricular tachycardia, pauses greater than 2 seconds or advanced atrioventricular block were classified as significant arrhythmia. The association between symptoms and significant arrhythmias were analyzed. Results The web-loop recorded arrhythmic symptoms in 74 (66%) patients. Of these, in only 14 (19%) patients the association between symptoms and significant cardiac arrhythmia was detected. Moreover, significant arrhythmia was found in 11 (9.8%) asymptomatic patients. There was no association between presence of major symptoms and significant cardiac arrhythmia (OR=0.57, CI95%: 0.21-1.57; p=0.23). Conclusion We found no association between major symptoms and significant cardiac arrhythmia in patients submitted to event recorder monitoring. Event loop recorder was useful to elucidate cases of palpitations and syncope in symptomatic patients. PMID:25295448

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

Antolin, P.; Vissers, G.; Shibata, K., E-mail: antolin@astro.uio.n, E-mail: g.j.m.vissers@astro.uio.n, E-mail: shibata@kwasan.kyoto-u.ac.j

Reported observations in H{alpha}, Ca II H, and K or other chromospheric lines of coronal rain trace back to the days of the Skylab mission. Corresponding to cool and dense plasma, coronal rain is often observed falling down along coronal loops in active regions. A physical explanation for this spectacular phenomenon has been put forward thanks to numerical simulations of loops with footpoint-concentrated heating, a heating scenario in which cool condensations naturally form in the corona. This effect has been termed 'catastrophic cooling' and is the predominant explanation for coronal rain. In this work, we further investigate the link betweenmore » this phenomenon and the heating mechanisms acting in the corona. We start by analyzing observations of coronal rain at the limb in the Ca II H line performed by the Hinode satellite, and derive interesting statistical properties concerning the dynamics. We then compare the observations with 1.5-dimensional MHD simulations of loops being heated by small-scale discrete events concentrated toward the footpoints (that could come, for instance, from magnetic reconnection events), and by Alfven waves generated at the photospheric level. Both our observation and simulation results suggest that coronal rain is a far more common phenomenon than previously thought. Also, we show that the structure and dynamics of condensations are far more sensitive to the internal pressure changes in loops than to gravity. Furthermore, it is found that if a loop is predominantly heated from Alfven waves, coronal rain is inhibited due to the characteristic uniform heating they produce. Hence, coronal rain may not only point to the spatial distribution of the heating in coronal loops but also to the agent of the heating itself. We thus propose coronal rain as a marker for coronal heating mechanisms.« less

Slow Magnetosonic Waves and Fast Flows in Active Region Loops

NASA Technical Reports Server (NTRS)

Ofman, L.; Wang, T. J.; Davila, J. M.

2012-01-01

Recent extreme ultraviolet spectroscopic observations indicate that slow magnetosonic waves are present in active region (AR) loops. Some of the spectral data were also interpreted as evidence of fast (approx 100-300 km/s) quasiperiodic flows. We have performed three-dimensional magnetohydrodynamic (3D MHD) modeling of a bipolar AR that contains impulsively generated waves and flows in coronal loops. The model AR is initiated with a dipole magnetic field and gravitationally stratified density, with an upflow-driven steadily or periodically in localized regions at the footpoints of magnetic loops. The resulting flows along the magnetic field lines of the AR produce higher density loops compared to the surrounding plasma by injection of material into the flux tubes and the establishment of siphon flow.We find that the impulsive onset of flows with subsonic speeds result in the excitation of damped slow magnetosonic waves that propagate along the loops and coupled nonlinearly driven fast-mode waves. The phase speed of the slow magnetosonic waves is close to the coronal sound speed. When the amplitude of the driving pulses is increased we find that slow shock-like wave trains are produced. When the upflows are driven periodically, undamped oscillations are produced with periods determined by the periodicity of the upflows. Based on the results of the 3D MHD model we suggest that the observed slow magnetosonic waves and persistent upflows may be produced by the same impulsive events at the bases of ARs.

Psychophysiological Control of Acognitive Task Using Adaptive Automation

NASA Technical Reports Server (NTRS)

Freeman, Frederick; Pope, Alan T. (Technical Monitor)

2001-01-01

The major focus of the present proposal was to examine psychophysiological variables related to hazardous states of awareness induced by monitoring automated systems. With the increased use of automation in today's work environment, people's roles in the work place are being redefined from that of active participant to one of passive monitor. Although the introduction of automated systems has a number of benefits, there are also a number of disadvantages regarding worker performance. Byrne and Parasuraman have argued for the use of psychophysiological measures in the development and the implementation of adaptive automation. While both performance based and model based adaptive automation have been studied, the use of psychophysiological measures, especially EEG, offers the advantage of real time evaluation of the state of the subject. The current study used the closed-loop system, developed at NASA-Langley Research Center, to control the state of awareness of subjects while they performed a cognitive vigilance task. Previous research in our laboratory, supported by NASA, has demonstrated that, in an adaptive automation, closed-loop environment, subjects perform a tracking task better under a negative than a positive, feedback condition. In addition, this condition produces less subjective workload and larger P300 event related potentials to auditory stimuli presented in a concurrent oddball task. We have also recently shown that the closed-loop system used to control the level of automation in a tracking task can also be used to control the event rate of stimuli in a vigilance monitoring task. By changing the event rate based on the subject's index of arousal, we have been able to produce improved monitoring, relative to various control groups. We have demonstrated in our initial closed-loop experiments with the the vigilance paradigm that using a negative feedback contingency (i.e. increasing event rates when the EEG index is low and decreasing event rates when the EEG index is high) results in a marked decrease of the vigilance decrement over a 40 minute session. This effect is in direct contrast to performance of a positive feedback group, as well as a number of other control groups which demonstrated the typical vigilance decrement. Interestingly, however, the negative feedback group performed at virtually the same level as a yoked control group. The yoked control group received the same order of changes in event rate that were generated by the negative feedback subjects using the closed-loop system. Thus it would appear to be possible to optimize vigilance performance by controlling the stimuli which subjects are asked to process.

The Cygnus Loop: An Older Supernova Remnant.

ERIC Educational Resources Information Center

Straka, William

1987-01-01

Describes the Cygnus Loop, one of brightest and most easily studied of the older "remnant nebulae" of supernova outbursts. Discusses some of the historical events surrounding the discovery and measurement of the Cygnus Loop and makes some projections on its future. (TW)

Mass motions in impulsive flarelike brightenings as observed by OSO 8. [mechanism response for solar flares

NASA Technical Reports Server (NTRS)

Bruner, E. C., Jr.; Lites, B. W.

1979-01-01

C IV 1548-A line profiles obtained with the University of Colorado spectrometer aboard OSO 8 reveal transient, redshifted brightenings in the chromosphere-corona transition region above active regions and sunspots. In these events the intensity rises by factors of up to 5 in less than the profile sampling interval of 27 sec. These events indicate that the emitting material is moving downward at velocities of up to 30 km/sec. The increase in line intensity and the amount of motion are consistent with the interpretation of these events as pressure waves propagating down magnetic flux loops.

Solar Tutorial and Annotation Resource (STAR)

NASA Astrophysics Data System (ADS)

Showalter, C.; Rex, R.; Hurlburt, N. E.; Zita, E. J.

2009-12-01

We have written a software suite designed to facilitate solar data analysis by scientists, students, and the public, anticipating enormous datasets from future instruments. Our “STAR" suite includes an interactive learning section explaining 15 classes of solar events. Users learn software tools that exploit humans’ superior ability (over computers) to identify many events. Annotation tools include time slice generation to quantify loop oscillations, the interpolation of event shapes using natural cubic splines (for loops, sigmoids, and filaments) and closed cubic splines (for coronal holes). Learning these tools in an environment where examples are provided prepares new users to comfortably utilize annotation software with new data. Upon completion of our tutorial, users are presented with media of various solar events and asked to identify and annotate the images, to test their mastery of the system. Goals of the project include public input into the data analysis of very large datasets from future solar satellites, and increased public interest and knowledge about the Sun. In 2010, the Solar Dynamics Observatory (SDO) will be launched into orbit. SDO’s advancements in solar telescope technology will generate a terabyte per day of high-quality data, requiring innovation in data management. While major projects develop automated feature recognition software, so that computers can complete much of the initial event tagging and analysis, still, that software cannot annotate features such as sigmoids, coronal magnetic loops, coronal dimming, etc., due to large amounts of data concentrated in relatively small areas. Previously, solar physicists manually annotated these features, but with the imminent influx of data it is unrealistic to expect specialized researchers to examine every image that computers cannot fully process. A new approach is needed to efficiently process these data. Providing analysis tools and data access to students and the public have proven efficient in similar astrophysical projects (e.g. the “Galaxy Zoo.”) For “crowdsourcing” to be effective for solar research, the public needs knowledge and skills to recognize and annotate key events on the Sun. Our tutorial can provide this training, with over 200 images and 18 movies showing examples of active regions, coronal dimmings, coronal holes, coronal jets, coronal waves, emerging flux, sigmoids, coronal magnetic loops, filaments, filament eruption, flares, loop oscillation, plage, surges, and sunspots. Annotation tools are provided for many of these events. Many features of the tutorial, such as mouse-over definitions and interactive annotation examples, are designed to assist people without previous experience in solar physics. After completing the tutorial, the user is presented with an interactive quiz: a series of movies and images to identify and annotate. The tutorial teaches the user, with feedback on correct and incorrect answers, until the user develops appropriate confidence and skill. This prepares users to annotate new data, based on their experience with event recognition and annotation tools. Trained users can contribute significantly to our data analysis tasks, even as our training tool contributes to public science literacy and interest in solar physics.

Spacecraft-to-Earth Communications for Juno and Mars Science Laboratory Critical Events

NASA Technical Reports Server (NTRS)

Soriano, Melissa; Finley, Susan; Jongeling, Andre; Fort, David; Goodhart, Charles; Rogstad, David; Navarro, Robert

2012-01-01

Deep Space communications typically utilize closed loop receivers and Binary Phase Shift Keying (BPSK) or Quadrature Phase Shift Keying (QPSK). Critical spacecraft events include orbit insertion and entry, descent, and landing.---Low gain antennas--> low signal -to-noise-ratio.---High dynamics such as parachute deployment or spin --> Doppler shift. During critical events, open loop receivers and Multiple Frequency Shift Keying (MFSK) used. Entry, Descent, Landing (EDL) Data Analysis (EDA) system detects tones in real-time.

Method-Unifying View of Loop-Formation Kinetics in Peptide and Protein Folding.

PubMed

Jacob, Maik H; D'Souza, Roy N; Schwarzlose, Thomas; Wang, Xiaojuan; Huang, Fang; Haas, Elisha; Nau, Werner M

2018-04-26

Protein folding can be described as a probabilistic succession of events in which the peptide chain forms loops closed by specific amino acid residue contacts, herein referred to as loop nodes. To measure loop rates, several photophysical methods have been introduced where a pair of optically active probes is incorporated at selected chain positions and the excited probe undergoes contact quenching (CQ) upon collision with the second probe. The quenching mechanisms involved triplet-triplet energy transfer, photoinduced electron transfer, and collision-induced fluorescence quenching, where the fluorescence of Dbo, an asparagine residue conjugated to 2,3-diazabicyclo[2.2.2]octane, is quenched by tryptophan. The discrepancy between the loop rates afforded from these three CQ techniques has, however, remained unresolved. In analyzing this discrepancy, we now report two short-distance FRET methods where Dbo acts as an energy acceptor in combination with tryptophan and naphtylalanine, two donors with largely different fluorescence lifetimes of 1.3 and 33 ns, respectively. Despite the different quenching mechanisms, the rates from FRET and CQ methods were, surprisingly, of comparable magnitude. This combination of FRET and CQ data led to a unifying physical model and to the conclusion that the rate of loop formation in folding reactions varies not only with the kind and number of residues that constitute the chain but also in particular with the size and properties of the residues that constitute the loop node.

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W

2018-01-01

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807

Replication stress induces accumulation of FANCD2 at central region of large fragile genes

PubMed Central

Okamoto, Yusuke; Iwasaki, Watal M; Kugou, Kazuto; Takahashi, Kazuki K; Oda, Arisa; Sato, Koichi; Kobayashi, Wataru; Kawai, Hidehiko; Sakasai, Ryo; Takaori-Kondo, Akifumi; Yamamoto, Takashi; Kanemaki, Masato T; Taoka, Masato; Isobe, Toshiaki; Kurumizaka, Hitoshi; Innan, Hideki; Ohta, Kunihiro; Ishiai, Masamichi; Takata, Minoru

2018-01-01

Abstract During mild replication stress provoked by low dose aphidicolin (APH) treatment, the key Fanconi anemia protein FANCD2 accumulates on common fragile sites, observed as sister foci, and protects genome stability. To gain further insights into FANCD2 function and its regulatory mechanisms, we examined the genome-wide chromatin localization of FANCD2 in this setting by ChIP-seq analysis. We found that FANCD2 mostly accumulates in the central regions of a set of large transcribed genes that were extensively overlapped with known CFS. Consistent with previous studies, we found that this FANCD2 retention is R-loop-dependent. However, FANCD2 monoubiquitination and RPA foci formation were still induced in cells depleted of R-loops. Interestingly, we detected increased Proximal Ligation Assay dots between FANCD2 and R-loops following APH treatment, which was suppressed by transcriptional inhibition. Collectively, our data suggested that R-loops are required to retain FANCD2 in chromatin at the middle intronic region of large genes, while the replication stress-induced upstream events leading to the FA pathway activation are not triggered by R-loops. PMID:29394375

Solar Coronal Loop Dynamics Near the Null Point Above Active Region NOAA 2666

NASA Astrophysics Data System (ADS)

Filippov, B.

2018-06-01

We analyse observations of a saddle-like structure in the corona above the western limb of the Sun on 2017 July 18. The structure was clearly outlined by coronal loops with typical coronal temperature no more than 1 MK. The dynamics of loops showed convergence towards the centre of the saddle in the vertical direction and divergence in the horizontal direction. The event is a clear example of smooth coronal magnetic field reconnection. No heating manifestations in the reconnection region or magnetically connected areas were observed. Potential magnetic field calculations, which use as the boundary condition the SDO/HMI magnetogram taken on July 14, showed the presence of a null point at the height of 122 arcsec above the photosphere just at the centre of the saddle structure. The shape of field lines fits the fan-spine magnetic configuration above NOAA 2666.

Evidence for two-loop interaction from IRIS and SDO observations of penumbral brightenings

NASA Astrophysics Data System (ADS)

Alissandrakis, C. E.; Koukras, A.; Patsourakos, S.; Nindos, A.

2017-07-01

Aims: We investigate small scale energy release events which can provide clues on the heating mechanism of the solar corona. Methods: We analyzed spectral and imaging data from the Interface Region Imaging Spectrograph (IRIS), images from the Atmospheric Imaging Assembly (AIA) aboard the Solar Dynamics Observatoty (SDO), and magnetograms from the Helioseismic and Magnetic Imager (HMI) aboard SDO. Results: We report observations of small flaring loops in the penumbra of a large sunspot on July 19, 2013. Our main event consisted of a loop spanning 15'', from the umbral-penumbral boundary to an opposite polarity region outside the penumbra. It lasted approximately 10 min with a two minute impulsive peak and was observed in all AIA/SDO channels, while the IRIS slit was located near its penumbral footpoint. Mass motions with an apparent velocity of 100 km s-1 were detected beyond the brightening, starting in the rise phase of the impulsive peak; these were apparently associated with a higher-lying loop. We interpret these motions in terms of two-loop interaction. IRIS spectra in both the C II and Si iv lines showed very extended wings, up to about 400 km s-1, first in the blue (upflows) and subsequently in the red wing. In addition to the strong lines, emission was detected in the weak lines of Cl I, O I and C I, as well as in the Mg II triplet lines. Absorption features in the profiles of the C II doublet, the Si iv doublet and the Mg II h and k lines indicate the existence of material with a lower source function between the brightening and the observer. We attribute this absorption to the higher loop and this adds further credibility to the two-loop interaction hypothesis. Tilts were detected in the absorption spectra, as well as in the spectra of Cl I, O I, and C I lines, possibly indicating rotational motions from the untwisting of magnetic flux tubes. Conclusions: We conclude that the absorption features in the C II, Si iv and Mg II profiles originate in a higher-lying, descending loop; as this approached the already activated lower-lying loop, their interaction gave rise to the impulsive peak, the very broad line profiles and the mass motions. Movies associated to Figs. A.1-A.3 are available at http://www.aanda.org

Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

NASA Astrophysics Data System (ADS)

Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

2013-09-01

Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

EVIDENCE FOR COLLAPSING FIELDS IN THE CORONA AND PHOTOSPHERE DURING THE 2011 FEBRUARY 15 X2.2 FLARE: SDO/AIA AND HMI OBSERVATIONS

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

Gosain, S., E-mail: sgosain@nso.edu; Udaipur Solar Observatory, P.O. Box 198, Dewali, Udaipur, Rajasthan 313001

2012-04-10

We use high-resolution Solar Dynamics Observatory (SDO)/Atmospheric Imaging Assembly observations to study the evolution of the coronal loops in a flaring solar active region, NOAA 11158. We identify three distinct phases of the coronal loop dynamics during this event: (1) slow-rise phase: slow rising motion of the loop-tops prior to the flare in response to the slow rise of the underlying flux rope; (2) collapse phase: sudden contraction of the loop-tops, with the lower loops collapsing earlier than the higher loops; and (3) oscillation phase: the loops exhibit global kink oscillations after the collapse phase at different periods, with themore » period decreasing with the decreasing height of the loops. The period of these loop oscillations is used to estimate the field strength in the coronal loops. Furthermore, we also use SDO/Helioseismic and Magnetic Imager (HMI) observations to study the photospheric changes close to the polarity inversion line (PIL). The longitudinal magnetograms show a stepwise permanent decrease in the magnetic flux after the flare over a coherent patch along the PIL. Furthermore, we examine the HMI Stokes I, Q, U, V profiles over this patch and find that the Stokes-V signal systematically decreases while the Stokes-Q and U signals increase after the flare. These observations suggest that close to the PIL the field configuration became more horizontal after the flare. We also use HMI vector magnetic field observations to quantify the changes in the field inclination angle and find an inward collapse of the field lines toward the PIL by {approx}10 Degree-Sign . These observations are consistent with the 'coronal implosion' scenario and its predictions about flare-related photospheric field changes.« less

Neuromimetic Event-Based Detection for Closed-Loop Tactile Feedback Control of Upper Limb Prostheses

PubMed Central

Osborn, Luke; Kaliki, Rahul; Soares, Alcimar; Thakor, Nitish

2016-01-01

Upper limb amputees lack the valuable tactile sensing that helps provide context about the surrounding environment. Here we utilize tactile information to provide active touch feedback to a prosthetic hand. First, we developed fingertip tactile sensors for producing biomimetic spiking responses for monitoring contact, release, and slip of an object grasped by a prosthetic hand. We convert the sensor output into pulses, mimicking the rapid and slowly adapting spiking responses of receptor afferents found in the human body. Second, we designed and implemented two neuromimetic event-based algorithms, Compliant Grasping and Slip Prevention, on a prosthesis to create a local closed-loop tactile feedback control system (i.e. tactile information is sent to the prosthesis). Grasping experiments were designed to assess the benefit of this biologically inspired neuromimetic tactile feedback to a prosthesis. Results from able-bodied and amputee subjects show the average number of objects that broke or slipped during grasping decreased by over 50% and the average time to complete a grasping task decreased by at least 10% for most trials when comparing neuromimetic tactile feedback with no feedback on a prosthesis. Our neuromimetic method of closed-loop tactile sensing is a novel approach to improving the function of upper limb prostheses. PMID:27777640

Symmetry breaking and polarity establishment during mouse oocyte maturation

PubMed Central

Yi, Kexi; Rubinstein, Boris; Li, Rong

2013-01-01

Mammalian oocyte meiosis encompasses two rounds of asymmetric divisions to generate a totipotent haploid egg and, as by-products, two small polar bodies. Two intracellular events, asymmetric spindle positioning and cortical polarization, are critical to such asymmetric divisions. Actin but not microtubule cytoskeleton has been known to be directly involved in both events. Recent work has revealed a positive feedback loop between chromosome-mediated cortical activation and the Arp2/3-orchestrated cytoplasmic streaming that moves chromosomes. This feedback loop not only maintains meiotic II spindle position during metaphase II arrest, but also brings about symmetry breaking during meiosis I. Prior to an Arp2/3-dependent phase of fast movement, meiotic I spindle experiences a slow and non-directional first phase of migration driven by a pushing force from Fmn2-mediated actin polymerization. In addition to illustrating these molecular mechanisms, mathematical simulations are presented to elucidate mechanical properties of actin-dependent force generation in this system. PMID:24062576

Design strategies for dynamic closed-loop optogenetic neurocontrol in vivo

NASA Astrophysics Data System (ADS)

Bolus, M. F.; Willats, A. A.; Whitmire, C. J.; Rozell, C. J.; Stanley, G. B.

2018-04-01

Objective. Controlling neural activity enables the possibility of manipulating sensory perception, cognitive processes, and body movement, in addition to providing a powerful framework for functionally disentangling the neural circuits that underlie these complex phenomena. Over the last decade, optogenetic stimulation has become an increasingly important and powerful tool for understanding neural circuit function, owing to the ability to target specific cell types and bidirectionally modulate neural activity. To date, most stimulation has been provided in open-loop or in an on/off closed-loop fashion, where previously-determined stimulation is triggered by an event. Here, we describe and demonstrate a design approach for precise optogenetic control of neuronal firing rate modulation using feedback to guide stimulation continuously. Approach. Using the rodent somatosensory thalamus as an experimental testbed for realizing desired time-varying patterns of firing rate modulation, we utilized a moving average exponential filter to estimate firing rate online from single-unit spiking measured extracellularly. This estimate of instantaneous rate served as feedback for a proportional integral (PI) controller, which was designed during the experiment based on a linear-nonlinear Poisson (LNP) model of the neuronal response to light. Main results. The LNP model fit during the experiment enabled robust closed-loop control, resulting in good tracking of sinusoidal and non-sinusoidal targets, and rejection of unmeasured disturbances. Closed-loop control also enabled manipulation of trial-to-trial variability. Significance. Because neuroscientists are faced with the challenge of dissecting the functions of circuit components, the ability to maintain control of a region of interest in spite of changes in ongoing neural activity will be important for disambiguating function within networks. Closed-loop stimulation strategies are ideal for control that is robust to such changes, and the employment of continuous feedback to adjust stimulation in real-time can improve the quality of data collected using optogenetic manipulation.

Active Control of Solar Array Dynamics During Spacecraft Maneuvers

NASA Technical Reports Server (NTRS)

Ross, Brant A.; Woo, Nelson; Kraft, Thomas G.; Blandino, Joseph R.

2016-01-01

Recent NASA mission plans require spacecraft to undergo potentially significant maneuvers (or dynamic loading events) with large solar arrays deployed. Therefore there is an increased need to understand and possibly control the nonlinear dynamics in the spacecraft system during such maneuvers. The development of a nonlinear controller is described. The utility of using a nonlinear controller to reduce forces and motion in a solar array wing during a loading event is demonstrated. The result is dramatic reductions in system forces and motion during a 10 second loading event. A motion curve derived from the simulation with the closed loop controller is used to obtain similar benefits with a simpler motion control approach.

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Fonarow, Gregg C; Jaski, Brian E; Bart, Bradley A; Heywood, J Thomas; Nabut, Jose L; Schollmeyer, Michael P

2015-09-01

In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure. Copyright © 2015. Published by Elsevier Inc.

Molecular genetic analysis of circadian timekeeping in Drosophila

PubMed Central

Hardin, Paul E.

2014-01-01

A genetic screen for mutants that alter circadian rhythms in Drosophila identified the first clock gene - the period (per) gene. The per gene is a central player within a transcriptional feedback loop that represents the core mechanism for keeping circadian time in Drosophila and other animals. The per feedback loop, or core loop, is interlocked with the Clock (Clk) feedback loop, but whether the Clk feedback loop contributes to circadian timekeeping is not known. A series of distinct molecular events are thought to control transcriptional feedback in the core loop. The time it takes to complete these events should take much less than 24h, thus delays must be imposed at different steps within the core loop. As new clock genes are identified, the molecular mechanisms responsible for these delays have been revealed in ever-increasing detail, and provide an in depth accounting of how transcriptional feedback loops keep circadian time. The phase of these feedback loops shift to maintain synchrony with environmental cycles, the most reliable of which is light. Although a great deal is known about cell-autonomous mechanisms of light-induced phase shifting by CRYPTOCHROME (CRY), much less is known about non-cell autonomous mechanisms. CRY mediates phase shifts through an uncharacterized mechanism in certain brain oscillator neurons, and carries out a dual role as a photoreceptor and transcription factor in other tissues. Here I will review how transcriptional feedback loops function to keep time in Drosophila, how they impose delays to maintain a 24h cycle, and how they maintain synchrony with environmental light:dark cycles. The transcriptional feedback loops that keep time in Drosophila are well conserved in other animals, thus what we learn about these loops in Drosophila should continue to provide insight into the operation of analogous transcriptional feedback loops in other animals. PMID:21924977

Flat microwave spectra seen at X-class flares

NASA Technical Reports Server (NTRS)

Lee, Jeongwoo W.; Gary, Dale E.; Zirin, H.

1994-01-01

We report peculiar spectral activity of four large microwave bursts as obtained from the Solar Arrays at the Owens Valey Radio Observatory during observations of X-class flares on 24 May 1990 and 7, 8, 22 March 1991. Main observational points that we newly uncovered are: (1) flat flux spectra over 1-18 GHz in large amounts of flux ranging from 10(exp 2) to 10(exp 4) s.f.u. at the maximum phase, (2) a common evolutionary pattern in which the spectral region of dominant flux shifts from high frequencies at the initial rise to low frequencies at the decaying phase, and (3) unusual time profiles that are impulsive at high frequencies but more extended at lower frequencies. We carry out the model calculations of microwave spectra under assumptions of gyrosynchrotron mechanism and a dipole field configuration to reproduce the observational characteristics. Our results are summarized as follows. First, a flat microwave spectrum reaching up to 10(exp 2) - 10(exp 4) s.f.u. may occur in a case where a magnetic loop is extended to an angular size of approximately (0.7-7.0) x 10(exp -7) sterad and contains a huge number (N(E greater than 10 keV) approx. 10(exp 36) - 10(exp 38)) of nonthermal electrons with power-law index approx. 3-3.5 over the entire volume. Second, the observed spectral activity could adequately be accounted for by the shrinking of the region of nonthermal electrons to the loop top and by the softening of the power-law spectrum of electrons in a time scale ranging 3-45 min depending on the event. Third, the extended microwave activity at lower frequencies is probably due to electrons trapped in the loop top where magnetic fields are low. Finally, we clarify the physical distinction between these large, extended microwave bursts and the gradual/post-microwave bursts often seen in weak events, both of which are characterized by long-period activity and broadband spectra.

Design and Test of an Event Detector for the ReflectoActive Seals System

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

Stinson, Brad J

2006-05-01

The purpose of this thesis was to research, design, develop and test a novel instrument for detecting fiber optic loop continuity and spatially locating fiber optic breaches. The work is for an active seal system called ReflectoActive Seals whose purpose is to provide real time container tamper indication. A Field Programmable Gate Array was used to implement a loop continuity detector and a spatial breach locator based on a high acquisition speed single photon counting optical time domain reflectometer. Communication and other control features were added in order to create a usable instrument that met defined requirements. A host graphicalmore » user interface was developed to illustrate system use and performance. The resulting device meets performance specifications by exhibiting a dynamic range of 27dB and a spatial resolution of 1.5 ft. The communication scheme used expands installation options and allows the device to communicate to a central host via existing Local Area Networks and/or the Internet.« less

Design and Test of an Event Detector and Locator for the ReflectoActive Seals System

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

Stinson, Brad J

2006-06-01

The purpose of this work was to research, design, develop and test a novel instrument for detecting fiber optic loop continuity and spatially locating fiber optic breaches. The work is for an active seal system called ReflectoActive{trademark} Seals whose purpose is to provide real time container tamper indication. A Field Programmable Gate Array was used to implement a loop continuity detector and a spatial breach locator based on a high acquisition speed single photon counting optical time domain reflectometer. Communication and other control features were added in order to create a usable instrument that met defined requirements. A host graphicalmore » user interface was developed to illustrate system use and performance. The resulting device meets performance specifications by exhibiting a dynamic range of 27dB and a spatial resolution of 1.5 ft. The communication scheme used expands installation options and allows the device to communicate to a central host via existing Local Area Networks and/or the Internet.« less

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

Singh, K. A. P.; Nishida, K.; Shibata, K.

The recent discovery of chromospheric anemone jets with the Solar Optical Telescope (SOT) on board Hinode has shown an indirect evidence of magnetic reconnection in the solar chromosphere. However, the basic nature of magnetic reconnection in chromosphere is still unclear. We studied nine chromospheric anemone jets from SOT/Hinode using Ca II H filtergrams, and we found multiple bright, plasma ejections along the jets. In most cases, the major intensity enhancements (larger than 30% relative to the background intensity) of the loop correspond to the timing of the plasma ejections. The typical lifetime and size of the plasma ejecta are aboutmore » 20-60 s and 0.3-1.5 Mm, respectively. The height-time plot of jet shows many sub-structures (or individual jets) and the typical lifetime of the individual jet is about one to five minutes. Before the onset of the jet activity, a loop appears in Ca II H and gradually increases in size, and after few minutes several jets are launched from the loop. Once the jet activity starts and several individual jets are launched, the loop starts shrinking with a speed of {approx}4 km s{sup -1}. In some events, a downward moving blob with a speed of {approx}35 km s{sup -1} was observed, associated with the upward moving plasma along one of the legs of the loop hosting the jets. The upward moving plasma gradually developed into jets. Multiple plasma ejections in chromospheric anemone jet show the strongly time-dependent as well as intermittent nature of magnetic reconnection in the solar chromosphere.« less

Multiple Plasma Ejections and Intermittent Nature of Magnetic Reconnection in Solar Chromospheric Anemone Jets

NASA Astrophysics Data System (ADS)

Singh, K. A. P.; Isobe, H.; Nishizuka, N.; Nishida, K.; Shibata, K.

2012-11-01

The recent discovery of chromospheric anemone jets with the Solar Optical Telescope (SOT) on board Hinode has shown an indirect evidence of magnetic reconnection in the solar chromosphere. However, the basic nature of magnetic reconnection in chromosphere is still unclear. We studied nine chromospheric anemone jets from SOT/Hinode using Ca II H filtergrams, and we found multiple bright, plasma ejections along the jets. In most cases, the major intensity enhancements (larger than 30% relative to the background intensity) of the loop correspond to the timing of the plasma ejections. The typical lifetime and size of the plasma ejecta are about 20-60 s and 0.3-1.5 Mm, respectively. The height-time plot of jet shows many sub-structures (or individual jets) and the typical lifetime of the individual jet is about one to five minutes. Before the onset of the jet activity, a loop appears in Ca II H and gradually increases in size, and after few minutes several jets are launched from the loop. Once the jet activity starts and several individual jets are launched, the loop starts shrinking with a speed of ~4 km s-1. In some events, a downward moving blob with a speed of ~35 km s-1 was observed, associated with the upward moving plasma along one of the legs of the loop hosting the jets. The upward moving plasma gradually developed into jets. Multiple plasma ejections in chromospheric anemone jet show the strongly time-dependent as well as intermittent nature of magnetic reconnection in the solar chromosphere.

Influential factors of red-light running at signalized intersection and prediction using a rare events logistic regression model.

PubMed

Ren, Yilong; Wang, Yunpeng; Wu, Xinkai; Yu, Guizhen; Ding, Chuan

2016-10-01

Red light running (RLR) has become a major safety concern at signalized intersection. To prevent RLR related crashes, it is critical to identify the factors that significantly impact the drivers' behaviors of RLR, and to predict potential RLR in real time. In this research, 9-month's RLR events extracted from high-resolution traffic data collected by loop detectors from three signalized intersections were applied to identify the factors that significantly affect RLR behaviors. The data analysis indicated that occupancy time, time gap, used yellow time, time left to yellow start, whether the preceding vehicle runs through the intersection during yellow, and whether there is a vehicle passing through the intersection on the adjacent lane were significantly factors for RLR behaviors. Furthermore, due to the rare events nature of RLR, a modified rare events logistic regression model was developed for RLR prediction. The rare events logistic regression method has been applied in many fields for rare events studies and shows impressive performance, but so far none of previous research has applied this method to study RLR. The results showed that the rare events logistic regression model performed significantly better than the standard logistic regression model. More importantly, the proposed RLR prediction method is purely based on loop detector data collected from a single advance loop detector located 400 feet away from stop-bar. This brings great potential for future field applications of the proposed method since loops have been widely implemented in many intersections and can collect data in real time. This research is expected to contribute to the improvement of intersection safety significantly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unambiguous Evidence of Coronal Implosions during Solar Eruptions and Flares

NASA Astrophysics Data System (ADS)

Wang, Juntao; Simões, P. J. A.; Fletcher, L.

2018-05-01

In the implosion conjecture, coronal loops contract as the result of magnetic energy release in solar eruptions and flares. However, after almost two decades, observations of this phenomenon are still rare and most previous reports are plagued by projection effects so that loop contraction could be either true implosion or just a change in loop inclination. In this paper, to demonstrate the reality of loop contractions in the global coronal dynamics, we present four events with the continuously contracting loops in an almost edge-on geometry from the perspective of SDO/AIA, which are free from the ambiguity caused by the projection effects, also supplemented by contemporary observations from STEREO for examination. In the wider context of observations, simulations and theories, we argue that the implosion conjecture is valid in interpreting these events. Furthermore, distinct properties of the events allow us to identify two physical categories of implosion. One type demonstrates a rapid contraction at the beginning of the flare impulsive phase, as magnetic free energy is removed rapidly by a filament eruption. The other type, which has no visible eruption, shows a continuous loop shrinkage during the entire flare impulsive phase, which we suggest shows the ongoing conversion of magnetic free energy in a coronal volume. Corresponding scenarios are described that can provide reasonable explanations for the observations. We also point out that implosions may be suppressed in cases when a heavily mass-loaded filament is involved, possibly serving as an alternative account for their observational rarity.

DETECTION OF SUPERSONIC DOWNFLOWS AND ASSOCIATED HEATING EVENTS IN THE TRANSITION REGION ABOVE SUNSPOTS

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

Kleint, L.; Martínez-Sykora, J.; Antolin, P.

Interface Region Imaging Spectrograph data allow us to study the solar transition region (TR) with an unprecedented spatial resolution of 0.''33. On 2013 August 30, we observed bursts of high Doppler shifts suggesting strong supersonic downflows of up to 200 km s{sup –1} and weaker, slightly slower upflows in the spectral lines Mg II h and k, C II 1336, Si IV 1394 Å, and 1403 Å, that are correlated with brightenings in the slitjaw images (SJIs). The bursty behavior lasts throughout the 2 hr observation, with average burst durations of about 20 s. The locations of these short-lived events appear to bemore » the umbral and penumbral footpoints of EUV loops. Fast apparent downflows are observed along these loops in the SJIs and in the Atmospheric Imaging Assembly, suggesting that the loops are thermally unstable. We interpret the observations as cool material falling from coronal heights, and especially coronal rain produced along the thermally unstable loops, which leads to an increase of intensity at the loop footpoints, probably indicating an increase of density and temperature in the TR. The rain speeds are on the higher end of previously reported speeds for this phenomenon, and possibly higher than the free-fall velocity along the loops. On other observing days, similar bright dots are sometimes aligned into ribbons, resembling small flare ribbons. These observations provide a first insight into small-scale heating events in sunspots in the TR.« less

Radio-derived three-dimensional structure of a solar active region

NASA Astrophysics Data System (ADS)

Tun, Samuel D.

Solar active regions are the source of the most violent events observed on the Sun, some of which have a direct impact to modern civilization. Efforts to understand and predict such events require determination of the three-dimensional distributions of density, temperature, and magnetic fields above such active regions. This thesis presents the structure of the solar atmosphere above active region AR 10923, observed on 2006 Nov 10, as deduced from multi-wavelength studies including combined microwave observations from the Very Large Array (VLA) and the Owens Valley Solar Array (OVSA). The VLA observations provide excellent image quality at a few widely spaced frequencies while the OVSA data provide information at many intermediate frequencies to fill in the spectral coverage. In order to optimize the OVSA data for spectroscopic studies, the L1 method of self-calibration was implemented at this observatory, producing the best single frequency maps produced to date. Images at the 25 distinct, available frequencies are used to provide spatially resolved spectra along many lines of sight in the active region, from which microwave spectral diagnostics are obtained for deducing two-dimensional maps of temperature, magnetic field strength, and column density. The derived quantities are compared with multi-wavelength observations from SoHO and Hinode spacecraft, and with a standard potential magnetic field extrapolation. It is found that a two component temperature model is required to fit the data, in which a hot (> 2 MK) lower corona above the strong-field plage and sunspot regions (emitting via the gyroresonance process) is overlaid with somewhat cooler (˜ 1 MK) coronal loops that partially absorb the gyroresonance emission through the free-free (Bremsstrahlung) process. It is also found that the potential magnetic field extrapolation model can quantitatively account for the observed gyroresonance emission over most of the active region, but in a few areas a higher field strength is required. These areas of discrepancy are found to coincide with the foot points of hot X-ray loops over the sunspot's penumbra. The results and the extrapolation are used to explore the coronal configuration needed to explain the observations, from which it is found that the bulk of radio and X-ray free-free emission emanates from two loop systems, distinguished by the location of their loop foot points. The proposed stratification may explain the observed distribution of column emission measure and the differences in this quantity as obtained from X-rays or radio emission.

Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals New Structural Features and Insights into its Auto-phosphorylation.

PubMed

Kim, Kuglae; Cha, Jeong Seok; Cho, Yong-Soon; Kim, Hoyoung; Chang, Nienping; Kim, Hye-Jung; Cho, Hyun-Soo

2018-05-11

Dual-specificity tyrosine-regulated kinases (DYRKs) auto-phosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues. The auto-phosphorylation occurs intramolecularly and is a one-off event. DYRK3 is selectively expressed at a high level in hematopoietic cells and attenuates erythroblast development, leading to anemia. In the present study, we determined the crystal structure of the mature form of human DYRK3 in complex with harmine, an ATP competitive inhibitor. The crystal structure revealed a phosphorylation site, residue S350, whose phosphorylation increases the stability of DYRK3 and enhances its kinase activity. In addition, our structural and biochemical assays suggest that the N-terminal auto-phosphorylation accessory domain stabilizes the DYRK3 protein, followed by auto-phosphorylation of the tyrosine of the activation loop, which is important for kinase activity. Finally, our docking analysis provides information for the design of novel and potent therapeutics to treat anemia. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45.

PubMed

Courtney, Adam H; Amacher, Jeanine F; Kadlecek, Theresa A; Mollenauer, Marianne N; Au-Yeung, Byron B; Kuriyan, John; Weiss, Arthur

2017-08-03

The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck. Our findings reveal that modification of Y192 inhibits the ability of CD45 to associate with Lck in cells and dephosphorylate the C-terminal tail of Lck, which prevents its adoption of an active open conformation. These results suggest a negative feedback loop that responds to signaling events that tune active Lck amounts and TCR sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Single-Event Upset Characterization of Common First- and Second-Order All-Digital Phase-Locked Loops

NASA Astrophysics Data System (ADS)

Chen, Y. P.; Massengill, L. W.; Kauppila, J. S.; Bhuva, B. L.; Holman, W. T.; Loveless, T. D.

2017-08-01

The single-event upset (SEU) vulnerability of common first- and second-order all-digital-phase-locked loops (ADPLLs) is investigated through field-programmable gate array-based fault injection experiments. SEUs in the highest order pole of the loop filter and fraction-based phase detectors (PDs) may result in the worst case error response, i.e., limit cycle errors, often requiring system restart. SEUs in integer-based linear PDs may result in loss-of-lock errors, while SEUs in bang-bang PDs only result in temporary-frequency errors. ADPLLs with the same frequency tuning range but fewer bits in the control word exhibit better overall SEU performance.

FAST CONTRACTION OF CORONAL LOOPS AT THE FLARE PEAK

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

Liu Rui; Wang Haimin

On 2005 September 8, a coronal loop overlying the active region NOAA 10808 was observed in TRACE 171 A to contract at {approx}100 km s{sup -1} at the peak of an X5.4-2B flare at 21:05 UT. Prior to the fast contraction, the loop underwent a much slower contraction at {approx}6 km s{sup -1} for about 8 minutes, initiating during the flare preheating phase. The sudden switch to fast contraction is presumably corresponding to the onset of the impulsive phase. The contraction resulted in the oscillation of a group of loops located below, with the period of about 10 minutes. Meanwhile,more » the contracting loop exhibited a similar oscillatory pattern superimposed on the dominant downward motion. We suggest that the fast contraction reflects a suddenly reduced magnetic pressure underneath due either to (1) the eruption of magnetic structures located at lower altitudes or to (2) the rapid conversion of magnetic free energy in the flare core region. Electrons accelerated in the shrinking trap formed by the contracting loop can theoretically contribute to a late-phase hard X-ray burst, which is associated with Type IV radio emission. To complement the X5.4 flare which was probably confined, a similar event observed in SOHO/EIT 195 A on 2004 July 20 in an eruptive, M8.6 flare is briefly described, in which the contraction was followed by the expansion of the same loop leading up to a halo coronal mass ejection. These observations further substantiate the conjecture of coronal implosion and suggest coronal implosion as a new exciter mechanism for coronal loop oscillations.« less

An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction.

PubMed

Adams, Scott D; Kouzani, Abbas Z; Tye, Susannah J; Bennet, Kevin E; Berk, Michael

2018-02-13

Dynamic feedback based closed-loop medical devices offer a number of advantages for treatment of heterogeneous neurological conditions. Closed-loop devices integrate a level of neurobiological feedback, which allows for real-time adjustments to be made with the overarching aim of improving treatment efficacy and minimizing risks for adverse events. One target which has not been extensively explored as a potential feedback component in closed-loop therapies is mitochondrial function. Several neurodegenerative and psychiatric disorders including Parkinson's disease, Major Depressive disorder and Bipolar disorder have been linked to perturbations in the mitochondrial respiratory chain. This paper investigates the potential to monitor this mitochondrial function as a method of feedback for closed-loop neuromodulation treatments. A generic model of the closed-loop treatment is developed to describe the high-level functions of any system designed to control neural function based on mitochondrial response to stimulation, simplifying comparison and future meta-analysis. This model has four key functional components including: a sensor, signal manipulator, controller and effector. Each of these components are described and several potential technologies for each are investigated. While some of these candidate technologies are quite mature, there are still technological gaps remaining. The field of closed-loop medical devices is rapidly evolving, and whilst there is a lot of interest in this area, widespread adoption has not yet been achieved due to several remaining technological hurdles. However, the significant therapeutic benefits offered by this technology mean that this will be an active area for research for years to come.

Structure and Dynamics of Coronal Plasma

NASA Technical Reports Server (NTRS)

Golub, Leon

1998-01-01

Brief summaries of the four published papers produced within the present performance period of NASA Grant NAGW-4081 are presented. The full text of the papers are appended to the report. The first paper titled "Coronal Structures Observed in X-rays and H-alpa Structures" was published in the Kofu Symposium proceedings. The study analyzes cool and hot behavior of two x-ray events, a small flare and a surge. It was found that a large H-alpha surge appears in x-rays as a very weak event, while a weak H-alpha feature corresponds to the brightest x-ray emission on the disk at the time of the observation. Calculations of the heating necessary to produce these signatures, and implications for the driving and heating mechanisms of flares vs. surges are presented. The second paper "Differential Magnetic Field Shear in an Active Region" has been published in The Astrophysical Journal. The study compared the three dimensional extrapolation of magnetic fields with the observed coronal structure in an active region. Based on the fit between observed coronal structure throughout the volume of the region and the calculated magnetic field configurations, the authors propose a differential magnetic field shear model for this active region. The decreasing field shear in the outer portions of the AR may indicate a continual relaxation of the magnetic field with time, corresponding to a net transport of helicity outward. The third paper "Difficulties in Observing Coronal Structure" has been published in the journal Solar Physics. This paper discusses the evidence that the temperature and density structure of the corona are far more complicated than had previously been thought. The discussion is based on five studies carried out by the group on coronal plasma properties, showing that any one x-ray instrument does see all of the plasma present in the corona, that hot and cool material may appear to be co-spatial at a given location in the corona, and that simple magnetic field extrapolations provide only a poor fit to the observed structure. The fourth paper "Analysis and Comparison of Loop Structures Imaged with NIXT and Yohkoh/SXT" has been published in Astronomy and Astrophysics. This paper analyzes and compares a variety of coronal loops, deriving loop pressure and emission measure from loop models. They are able to determine the volume filling factor in the corona, which is found to be in the range 0.001 to 0.01 for compact loops, and of order 1 for large structures. The small values suggest highly filamented structures, especially at lower temperatures.

A Magnetic Reconnection Event in the Solar Atmosphere Driven by Relaxation of a Twisted Arch Filament System

NASA Astrophysics Data System (ADS)

Huang, Zhenghua; Mou, Chaozhou; Fu, Hui; Deng, Linhua; Li, Bo; Xia, Lidong

2018-02-01

We present high-resolution observations of a magnetic reconnection event in the solar atmosphere taken with the New Vacuum Solar Telescope, Atmospheric Imaging Assembly (AIA), and Helioseismic and Magnetic Imager (HMI). The reconnection event occurred between the threads of a twisted arch filament system (AFS) and coronal loops. Our observations reveal that the relaxation of the twisted AFS drives some of its threads to encounter the coronal loops, providing inflows of the reconnection. The reconnection is evidenced by flared X-shape features in the AIA images, a current-sheet-like feature apparently connecting post-reconnection loops in the Hα + 1 Å images, small-scale magnetic cancelation in the HMI magnetograms and flows with speeds of 40–80 km s‑1 along the coronal loops. The post-reconnection coronal loops seen in the AIA 94 Å passband appear to remain bright for a relatively long time, suggesting that they have been heated and/or filled up by dense plasmas previously stored in the AFS threads. Our observations suggest that the twisted magnetic system could release its free magnetic energy into the upper solar atmosphere through reconnection processes. While the plasma pressure in the reconnecting flux tubes are significantly different, the reconfiguration of field lines could result in transferring of mass among them and induce heating therein.

Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients with Chronic Kidney Disease.

PubMed

Nakano, Yusuke; Mizuno, Tomofumi; Niwa, Toru; Mukai, Kentaro; Wakabayashi, Hirokazu; Watanabe, Atsushi; Ando, Hirohiko; Takashima, Hiroaki; Murotani, Kenta; Waseda, Katsuhisa; Amano, Tetsuya

2018-01-27

Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in acute decompensated heart failure (HF) patients. However, there are limited data regarding the effect of continuous TLV administration on medium-term WRF.This was a retrospective observational study in hospitalized HF patients with chronic kidney disease (CKD). TLV was administered to those patients with fluid retention despite standard HF therapy. We compared 34 patients treated with TLV (TLV group) to 33 patients treated with conventional HF therapy with high-dose loop diuretics (furosemide ≥ 40 mg) (Loop group). Clinical outcomes, including the incidence of medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months after discharge and adverse events rate, were evaluated.Baseline patient characteristics were not different between the TLV and Loop group. The TLV group consisted of less frequent use of loop diuretics and carperitide compared with the Loop group. The incidence of medium-term WRF was significantly lower in the TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate logistic analysis showed that the TLV non-user was an independent predictor of medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous administration of TLV may reduce the risk of medium-term WRF, resulting possibility in improvement of long-term adverse outcomes in HF patients with CKD.

Evidence of thermal conduction depression in hot coronal loops

NASA Astrophysics Data System (ADS)

Wang, Tongjiang; Ofman, Leon; Sun, Xudong; Provornikova, Elena; Davila, Joseph

2015-08-01

Slow magnetoacoustic waves were first detected in hot (>6 MK) flare loops by the SOHO/SUMER spectrometer as Doppler shift oscillations in Fe XIX and Fe XXI lines. These oscillations are identified as standing slow-mode waves because the estimated phase speeds are close to the sound speed in the loop and some cases show a quarter period phase shift between velocity and intensity oscillations. The observed very rapid excitation and damping of standing slow mode waves have been studied by many authors using theories and numerical simulations, however, the exact mechanisms remain not well understood. Recently, flare-induced longitudinal intensity oscillations in hot post-flare loops have been detected by SDO/AIA. These oscillations have the similar physical properties as SUMER loop oscillations, and have been interpreted as the slow-mode waves. The multi-wavelength AIA observations with high spatio-temporal resolution and wide temperature coverage allow us to explore the wave excitation and damping mechanisms with an unprecedented detail to develope new coronal seismology. In this paper, we present accurate measurements of the effective adiabatic index (γeff) in the hot plasma from the electron temperature and density wave signals of a flare-induced longitudinal wave event using SDO/AIA data. Our results strikingly and clearly reveal that thermal conduction is highly depressed in hot (˜10 MK) post-flare loops and suggest that the compressive viscosity is the dominant wave damping mechanism which allows determination of the viscosity coefficient from the observables by coronal seismology. This new finding challenges our current understanding of thermal energy transport in solar and stellar flares, and may provide an alternative explanation of long-duration events and enhance our understand of coronal heating mechanism. We will discuss our results based on non-ideal MHD theory and simulations. We will also discuss the flare trigger mechanism based on magnetic topology derived from SDO/HMI vector magnetic fields using nonlinear force-free field extrapolations and discuss the wave excitation mechanism based on 3D MHD modeling of the active region.

Can Thermal Nonequilibrium Explain Coronal Loops?

NASA Technical Reports Server (NTRS)

Klimchuk, James A.; Karpen, Judy T.; Antiochos, Spiro K.

2010-01-01

Any successful model of coronal loops must explain a number of observed properties. For warm (approx. 1 MK) loops, these include: 1. excess density, 2. flat temperature profile, 3. super-hydrostatic scale height, 4. unstructured intensity profile, and 5. 1000-5000 s lifetime. We examine whether thermal nonequilibrium can reproduce the observations by performing hydrodynamic simulations based on steady coronal heating that decreases exponentially with height. We consider both monolithic and multi-stranded loops. The simulations successfully reproduce certain aspects of the observations, including the excess density, but each of them fails in at least one critical way. -Xonolithic models have far too much intensity structure, while multi-strand models are either too structured or too long-lived. Storms of nanoflares remain the only viable explanation for warm loops that has been proposed so far. Our results appear to rule out the widespread existence of heating that is both highly concentrated low in the corona and steady or quasi-steady (slowly varying or impulsive with a rapid cadence). Active regions would have a very different appearance if the dominant heating mechanism had these properties. Thermal nonequilibrium may nonetheless play an important role in prominences and catastrophic cooling e(veen.gts..,coronal rain) that occupy a small fraction of the coronal volume. However, apparent inconsistencies between the models and observations of cooling events have yet to be understood.

The Role of Quasi-Transverse Propagation in Observed Polarization of Flare Loop Microwave Radiation

NASA Astrophysics Data System (ADS)

Shain, A. V.; Melnikov, V. F.; Morgachev, A. S.

2017-12-01

The ordinary mode of gyrosynchrotron radiation was identified to be predominant in some segments of flare loops in solar flares of July 19, 2012, and October 22, 2014. These events were studied by investigation of the quasi-transverse propagation effect on the observed polarization. The analysis involved reconstruction of the magnetic field topology at the linear force-free approximation based on the data of the SDO HMI space telescope and the subsequent simulation of radio emission of flare loops with the GX Simulator software package. The quasi-transverse propagation effect was established to be characteristic for both events, but its influence on the radio emission polarization at a frequency of 17 GHz was observed only in the October 22, 2014 flare.

Time-resolved Emission from Bright Hot Pixels of an Active Region Observed in the EUV Band with SDO/AIA and Multi-stranded Loop Modeling

NASA Astrophysics Data System (ADS)

Tajfirouze, E.; Reale, F.; Petralia, A.; Testa, P.

2016-01-01

Evidence of small amounts of very hot plasma has been found in active regions and might be an indication of impulsive heating released at spatial scales smaller than the cross-section of a single loop. We investigate the heating and substructure of coronal loops in the core of one such active region by analyzing the light curves in the smallest resolution elements of solar observations in two EUV channels (94 and 335 Å) from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. We model the evolution of a bundle of strands heated by a storm of nanoflares by means of a hydrodynamic 0D loop model (EBTEL). The light curves obtained from a random combination of those of single strands are compared to the observed light curves either in a single pixel or in a row of pixels, simultaneously in the two channels, and using two independent methods: an artificial intelligent system (Probabilistic Neural Network) and a simple cross-correlation technique. We explore the space of the parameters to constrain the distribution of the heat pulses, their duration, their spatial size, and, as a feedback on the data, their signatures on the light curves. From both methods the best agreement is obtained for a relatively large population of events (1000) with a short duration (less than 1 minute) and a relatively shallow distribution (power law with index 1.5) in a limited energy range (1.5 decades). The feedback on the data indicates that bumps in the light curves, especially in the 94 Å channel, are signatures of a heating excess that occurred a few minutes before.

DIRECT OBSERVATIONS OF TETHER-CUTTING RECONNECTION DURING A MAJOR SOLAR EVENT FROM 2014 FEBRUARY 24 TO 25

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

Chen, Huadong; Zhang, Jun; Yang, Shuhong

2014-12-20

Using multi-wavelength data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we investigated two successive solar flares, a C5.1 confined flare and an X4.9 ejective flare with a halo coronal mass ejection, in NOAA active region 11990 from 2014 February 24 to 25. Before the confined flare onset, EUV brightening beneath the filament was detected. As the flare began, a twisted helical flux rope (FR) wrapping around the filament moved upward and then stopped, and in the meantime an obvious X-ray source below it was observed. Prior to the ejective X4.9 flare, some pre-existing loop structures inmore » the active region interacted with each other, which produced a brightening region beneath the filament. Meanwhile, a small flaring loop appeared below the interaction region and some new helical lines connecting the far ends of the loop structures were gradually formed and continually added into the former twisted FR. Then, due to the resulting imbalance between the magnetic pressure and tension, the new FR, together with the filament, erupted outward. Our observations coincide well with a tether-cutting model, suggesting that the two flares probably have the same triggering mechanism, i.e., tether-cutting reconnection. To our knowledge, this is the first direct observation of tether-cutting reconnection occurring between pre-existing loops in an active region. In the ejective flare case, the erupting filament exhibited an Ω-like kinked structure and underwent an exponential rise after a slow-rise phase, indicating that the kink instability might be also responsible for the eruption initiation.« less

An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis.

PubMed

Luo, Man-Li; Zhou, Zhuan; Sun, Lichao; Yu, Long; Sun, Lixin; Liu, Jun; Yang, Zhihua; Ran, Yuliang; Yao, Yandan; Hu, Hai

2018-05-28

Esophageal squamous cell carcinomas (ESCCs) have a poor prognosis mostly due to early metastasis. To explore the early event of metastasis in ESCC, we established an in vitro selection model to mimic the interaction of tumor cells with extracellular matrix, through which a sub-line of ESCC cells with high invasive ability was generated. By comparing the gene expression profile of the highly invasive sub-line to that of the parental cells, ADAM12-L was identified as a candidate gene promoting ESCC cell invasion. Immunohistochemistry revealed that the ADAM12-L was overexpressed in human ESCC tissues, especially at cancer invasive edge, and ADAM12-L overexpression tightly correlated with increased metastasis and poor outcome of ESCC patients. Indeed, ADAM12-L knockdown reduced the invasion and metastasis of ESCC cells both in vitro and in vivo. Furthermore, we demonstrated that ADAM12-L participated in focal adhesion turnover and promoted the activation of focal adhesion kinase (FAK), which in turn increased ADAM12-L transcription through FAK/JNK/c-Jun axis. Therefore, a loop initiated from the cancer cell upon the engagement with extracellular matrix through FAK and c-Jun to enhance ADAM12-L expression is established, leading to the positive feedback of further FAK activation and prompting metastasis. Our study indicates that overexpression of ADAM12-L can serve as a precision marker to determine the activation of this loop. Targeting ADAM12-L to disrupt this positive feedback loop represents a promising strategy to treat the metastasis of esophageal cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Temperature dependence of looping rates in a short peptide.

PubMed

Roccatano, Danilo; Sahoo, Harekrushna; Zacharias, Martin; Nau, Werner M

2007-03-15

Knowledge of the influence of chain length and amino acid sequence on the structural and dynamic properties of small peptides in solution provides essential information on protein folding pathways. The combination of time-resolved optical spectroscopy and molecular dynamics (MD) simulation methods has become a powerful tool to investigate the kinetics of end-to-end collisions (looping rates) in short peptides, which are relevant in early protein folding events. We applied the combination of both techniques to study temperature-dependent (280-340 K) looping rates of the Dbo-AlaGlyGln-Trp-NH2 peptide, where Dbo represents a 2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine, which served as a fluorescent probe in the time-resolved spectroscopic experiments. The experimental looping rates increased from 4.8 x 10(7) s(-1) at 283 K to 2.0 x 10(8) s(-1) at 338 K in H2O. The corresponding Arrhenius plot provided as activation parameters Ea = 21.5 +/- 1.0 kJ mol(-1) and ln(A/s-1) = 26.8 +/- 0.2 in H2O. The results in D2O were consistent with a slight solvent viscosity effect, i.e., the looping rates were 10-20% slower. MD simulations were performed with the GROMOS96 force field in a water solvent model, which required first a parametrization of the synthetic amino acid Dbo. After corrections for solvent viscosity effects, the calculated looping rates varied from 1.5 x 10(8) s(-1) at 280 K to 8.2 x 10(8) s(-1) at 340 K in H2O, which was about four times larger than the experimental data. The calculated activation parameters were Ea = 24.7 +/- 1.5 kJ mol(-1) and ln(A/s(-1)) = 29.4 +/- 0.1 in H2O.

Observational Signatures of Magnetic Reconnection in the Extended Corona

NASA Technical Reports Server (NTRS)

Savage, Sabrina; West, Matthew J.; Seaton, Daniel B.; Kobelski, Adam

2016-01-01

Observational signatures of reconnection have been studied extensively in the lower corona for decades, successfully providing insight into energy release mechanisms in the region above post-flare arcade loops and below 1.5 solar radii. During large eruptive events, however, energy release continues to occur well beyond the presence of reconnection signatures at these low heights. Supra-Arcade Downflows (SADs) and Supra-Arcade Downflowing Loops (SADLs) are particularly useful measures of continual reconnection in the corona as they may indicate the presence and path of retracting post-reconnection loops. SADs and SADLs have been faintly observed up to 18 hours beyond the passage of coronas mass ejections through the SOHO/LASCO field of view, but a recent event from 2014 October 14 associated with giant arches provides very clear observations of these downflows for days after the initial eruption. We report on this unique event and compare these findings with observational signatures of magnetic reconnection in the extended corona for more typical eruptions.

Observational Signatures of Magnetic Reconnection in the Extended Corona

NASA Technical Reports Server (NTRS)

Savage, Sabrina; West, Matthew J.; Seaton, Danial B.; Kobelski, Adam

2016-01-01

Observational signatures of reconnection have been studied extensively in the lower corona for decades, successfully providing insight into energy release mechanisms in the region above post-flare arcade loops and below 1.5 solar radii. During large eruptive events, however, energy release continues to occur well beyond the presence of reconnection signatures at these low heights. Supra-Arcade Downflows (SADs) and Supra-Arcade Downflowing Loops (SADLs) are particularly useful measures of continual reconnection in the corona as they may indicate the presence and path of retracting post-reconnection loops. SADs and SADLs have been faintly observed up to 18 hours beyond the passage of corona mass ejections through the SOHO/LASCO field of view, but a recent event from 2014 October 14 associated with giant arches provides very clear observations of these downflows for days after the initial eruption. We report on this unique event and compare these findings with observational signatures of magnetic reconnection in the extended corona for more typical eruptions.

Observational Signatures of Magnetic Reconnection in the Extended Corona

NASA Technical Reports Server (NTRS)

Savage, Sabrina; West, Matthew J.; Seaton, Daniel B.; Kobelski, Adam

2017-01-01

Observational signatures of reconnection have been studied extensively in the lower corona for decades, successfully providing insight into energy release mechanisms in the region above post-flare arcade loops and below 1.5 solar radii. During large eruptive events, however, energy release continues to occur well beyond the presence of reconnection signatures at these low heights. Supra-Arcade Downflows (SADs) and Supra-Arcade Downflowing Loops (SADLs) are particularly useful measures of continual reconnection in the corona as they may indicate the presence and path of retracting post-reconnection loops. SADs and SADLs have been faintly observed up to 18 hours beyond the passage of corona mass ejections through the SOHO/LASCO field of view, but a recent event from 2014 October 14 associated with giant arches provides very clear observations of these downflows for days after the initial eruption. We report on this unique event and compare these findings with observational signatures of magnetic reconnection in the extended corona for more typical eruptions.

Simulations of Solar Jets Confined by Coronal Loops

NASA Technical Reports Server (NTRS)

Wyper, P. F.; De Vore, C. R.

2016-01-01

Coronal jets are collimated, dynamic events that occur over a broad range of spatial scales in the solar corona. In the open magnetic field of coronal holes, jets form quasi-radial spires that can extend far out into the heliosphere, while in closed-field regions the jet outflows are confined to the corona. We explore the application of the embedded-bipole model to jets occurring in closed coronal loops. In this model, magnetic free energy is injected slowly by footpoint motions that introduce twist within the closed dome of the jet source region, and is released rapidly by the onset of an ideal kink-like instability. Two length scales characterize the system: the width (N) of the jet source region and the footpoint separation (L) of the coronal loop that envelops the jet source. We find that both the conditions for initiation and the subsequent dynamics are highly sensitive to the ratio L/N. The longest-lasting and most energetic jets occur along long coronal loops with large L/N ratios, and share many of the features of open-field jets, while smaller L/N ratios produce shorter-duration, less energetic jets that are affected by reflections from the far-loop footpoint. We quantify the transition between these behaviors and show that our model replicates key qualitative and quantitative aspects of both quiet Sun and active-region loop jets. We also find that there connection between the closed dome and surrounding coronal loop is very extensive: the cumulative reconnected flux at least matches the total flux beneath the dome for small L/N, and is more than double that value for large L/N.

SIMULATIONS OF SOLAR JETS CONFINED BY CORONAL LOOPS

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

Wyper, P. F.; DeVore, C. R., E-mail: peter.f.wyper@nasa.gov, E-mail: c.richard.devore@nasa.gov

Coronal jets are collimated, dynamic events that occur over a broad range of spatial scales in the solar corona. In the open magnetic field of coronal holes, jets form quasi-radial spires that can extend far out into the heliosphere, while in closed-field regions the jet outflows are confined to the corona. We explore the application of the embedded-bipole model to jets occurring in closed coronal loops. In this model, magnetic free energy is injected slowly by footpoint motions that introduce twist within the closed dome of the jet source region, and is released rapidly by the onset of an idealmore » kink-like instability. Two length scales characterize the system: the width (N) of the jet source region and the footpoint separation (L) of the coronal loop that envelops the jet source. We find that both the conditions for initiation and the subsequent dynamics are highly sensitive to the ratio L/N. The longest-lasting and most energetic jets occur along long coronal loops with large L/N ratios, and share many of the features of open-field jets, while smaller L/N ratios produce shorter-duration, less energetic jets that are affected by reflections from the far-loop footpoint. We quantify the transition between these behaviors and show that our model replicates key qualitative and quantitative aspects of both quiet Sun and active-region loop jets. We also find that the reconnection between the closed dome and surrounding coronal loop is very extensive: the cumulative reconnected flux at least matches the total flux beneath the dome for small L/N, and is more than double that value for large L/N.« less

Analysis of Inter-Moss Loops in the Solar Region with IRIS and SDO AIA: Automatic Event Detection and Characterization

NASA Technical Reports Server (NTRS)

Fayock, Brian; Winebarger, Amy; De Pontieu, Bart; Alexander, Caroline

2016-01-01

The Interface Region Imaging Spectrograph (IRIS), launched in the summer of 2013, is designed specifically to observe and investigate the transition region and adjacent layers of the solar atmosphere, obtaining images in high spatial, temporal, and spectral resolution. Our particular work is focused on the evolution of inter-moss loops, which have been detected in the lower corona by the Atmospheric Imaging Assembly (AIA) and the High-Resolution Coronal Imager (Hi- C), but are known to have foot points below the transition region. With the high-resolution capabilities of IRIS and its Si IV pass band, which measures activity in the upper chromosphere, we can study these magnetic loops in detail and compare their characteristic length and time scales to those obtained from several AIA image sets, particularly the 171, 193, and 211 pass bands. By comparing the results between these four data sets, one can potentially establish a measure of the ionization equilibrium for the location in question. To explore this idea, we found a large, sit-and-stare observation within the IRIS database that fit our specifications. This data set contained a number of well-defined inter-moss loops (by visual inspection) with a cadence less than or equal to that of AIA (approximately 12 seconds). This particular data set was recorded on October 23, 2013 at 07:09:30, lasting for 3219 seconds with a field of view of 120.6 by 128.1 arcseconds, centered on -53.9 by 59.1 arcseconds from disk center. For ease of comparison, the AIA data has been interpolated to match the IRIS cadence and resolution. In the main portion of the poster, we demonstrate the detection of events, the information collected, and the immediate results to the right, showing the progress of an event with green as the start, blue as the peak, and red as the end. Below here, we demonstrate how pixels are combined to form groups. The 3D results are shown to the right

Analysis of Inter-Moss Loops in the Solar Region with IRIS and SDO AIA: Automatic Event Detection and Characterization

NASA Technical Reports Server (NTRS)

Fayock, Brian; Winebarger, Amy; De Pontieu, Bart

2014-01-01

The Interface Region Imaging Spectrograph (IRIS), launched in the summer of 2013, is designed specifically to observe and investigate the transition region and adjacent layers of the solar atmosphere, obtaining images in high spatial, temporal, and spectral resolution. Our particular work is focused on the evolution of inter-moss loops, which have been detected in the lower corona by the Atmospheric Imaging Assembly (AIA) and the High-Resolution Coronal Imager (Hi- C), but are known to have foot points below the transition region. With the high-resolution capabilities of IRIS and its Si IV pass band, which measures activity in the upper chromosphere, we can study these magnetic loops in detail and compare their characteristic length and time scales to those obtained from several AIA image sets, particularly the 171, 193, and 211 pass bands. By comparing the results between these four data sets, one can potentially establish a measure of the ionization equilibrium for the location in question. To explore this idea, we found a large, sit-and-stare observation within the IRIS database that fit our specifications. This data set contained a number of well-defined inter-moss loops (by visual inspection) with a cadence less than or equal to that of AIA (approximately 12 seconds). This particular data set was recorded on October 23, 2013 at 07:09:30, lasting for 3219 seconds with a field of view of 120.6 by 128.1 arcseconds, centered on -53.9 by 59.1 arcseconds from disk center. For ease of comparison, the AIA data has been interpolated to match the IRIS cadence and resolution. In the main portion of the poster, we demonstrate the detection of events, the information collected, and the immediate results to the right, showing the progress of an event with green as the start, blue as the peak, and red as the end. Below here, we demonstrate how pixels are combined to form groups. The 3D results are shown to the right.

Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes: A Comparative Effectiveness Study.

PubMed

Schroeder, Emily B; Chonchol, Michel; Shetterly, Susan M; Powers, J David; Adams, John L; Schmittdiel, Julie A; Nichols, Gregory A; O'Connor, Patrick J; Steiner, John F

2018-05-07

In individuals with diabetes, the comparative effectiveness of add-on antihypertensive medications added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on the risk of significant kidney events is unknown. We used an observational, multicenter cohort of 21,897 individuals with diabetes to compare individuals who added β -blockers, dihydropyridine calcium channel blockers, loop diuretics, or thiazide diuretics to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We examined the hazard of significant kidney events, cardiovascular events, and death using Cox proportional hazard models with propensity score weighting. The composite significant kidney event end point was defined as the first occurrence of a ≥30% decline in eGFR to an eGFR<60 ml/min per 1.73 m 2 , initiation of dialysis, or kidney transplant. The composite cardiovascular event end point was defined as the first occurrence of hospitalization for acute myocardial infarction, acute coronary syndrome, stroke, or congestive heart failure; coronary artery bypass grafting; or percutaneous coronary intervention, and it was only examined in those free of cardiovascular disease at baseline. Over a maximum of 5 years, there were 4707 significant kidney events, 1498 deaths, and 818 cardiovascular events. Compared with thiazide diuretics, hazard ratios for significant kidney events for β -blockers, calcium channel blockers, and loop diuretics were 0.81 (95% confidence interval, 0.74 to 0.89), 0.67 (95% confidence interval, 0.58 to 0.78), and 1.19 (95% confidence interval, 1.00 to 1.41), respectively. Compared with thiazide diuretics, hazard ratios of mortality for β -blockers, calcium channel blockers, and loop diuretics were 1.19 (95% confidence interval, 0.97 to 1.44), 0.73 (95% confidence interval, 0.52 to 1.03), and 1.67 (95% confidence interval, 1.31 to 2.13), respectively. Compared with thiazide diuretics, hazard ratios of cardiovascular events for β -blockers, calcium channel blockers, and loop diuretics compared with thiazide diuretics were 1.65 (95% confidence interval, 1.39 to 1.96), 1.05 (95% confidence interval, 0.80 to 1.39), and 1.55 (95% confidence interval, 1.05 to 2.27), respectively. Compared with thiazide diuretics, calcium channel blockers were associated with a lower risk of significant kidney events and a similar risk of cardiovascular events. Copyright © 2018 by the American Society of Nephrology.

Direct binding of arsenic trioxide to AMPK and generation of inhibitory effects on acute myeloid leukemia precursors

PubMed Central

Beauchamp, Elspeth M.; Kosciuczuk, Ewa M.; Serrano, Ruth; Nanavati, Dhaval; Swindell, Elden P.; Viollet, Benoit; O'Halloran, Thomas V.; Altman, Jessica K.; Platanias, Leonidas C.

2014-01-01

Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its anti-leukemic properties, remain to be defined. We provide evidence that arsenic can directly bind to cysteine 299 in AMPKα and inhibit its activity. This inhibition of AMPK by arsenic is required in part for its cytotoxic effects on primitive leukemic progenitors from patients with AML, while concomitant treatment with an AMPK activator antagonizes in vivo the arsenic-induced antileukemic effects in a xenograft AML mouse model. A consequence of AMPK inhibition is activation of the mTOR pathway as a negative regulatory feedback loop. However, when AMPK expression is lost, arsenic-dependent activation of the kinase RSK downstream of MAPK activity compensates the generation of regulatory feedback signals through phosphorylation of downstream mTOR targets. Thus, therapeutic regimens with arsenic trioxide will need to include inhibitors of both the mTOR and RSK pathways in combination to prevent engagement of negative feedback loops and maximize antineoplastic responses. PMID:25344585

Witnessing a Large-scale Slipping Magnetic Reconnection along a Dimming Channel during a Solar Flare

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

Jing, Ju; Lee, Jeongwoo; Xu, Yan

We report the intriguing large-scale dynamic phenomena associated with the M6.5 flare (SOL2015-06-22T18:23) in NOAA active region 12371, observed by RHESSI , Fermi , and the Atmospheric Image Assembly (AIA) and Magnetic Imager (HMI) on the Solar Dynamics Observatory ( SDO ). The most interesting feature of this event is a third ribbon (R3) arising in the decay phase, propagating along a dimming channel (seen in EUV passbands) toward a neighboring sunspot. The propagation of R3 occurs in the presence of hard X-ray footpoint emission and is broadly visible at temperatures from 0.6 MK to over 10 MK through themore » differential emission measure analysis. The coronal loops then undergo an apparent slipping motion following the same path of R3, after a ∼80 minute delay. To understand the underlying physics, we investigate the magnetic configuration and the thermal structure of the flaring region. Our results are in favor of a slipping-type reconnection followed by the thermodynamic evolution of coronal loops. In comparison with those previously reported slipping reconnection events, this one proceeds across a particularly long distance (∼60 Mm) over a long period of time (∼50 minutes) and shows two clearly distinguished phases: the propagation of the footpoint brightening driven by nonthermal particle injection and the apparent slippage of loops governed by plasma heating and subsequent cooling.« less

Electromechanical coupling of the solar atmosphere; Proceedings of the OSL Workshop, Capri, Italy, May 27-31, 1991

NASA Technical Reports Server (NTRS)

Spicer, Daniel S. (Editor); Macneice, Peter (Editor)

1992-01-01

The present conference discusses the role of magnetic flux tubes as communication channels, flux tube sizes and their temporal evolution, magnetic field line topology in the solar active regions, weak solar magnetic fields, explosive events and magnetic reconnection in the solar atmosphere, and 3D kinematic reconnection of plasmoids with nulls. Also discussed are coronal heating mechanisms, coronal heating through a lack of MHD equilibrium, Alfven waves in current-carrying inhomogeneous plasmas, hydrostatic models of X-ray coronal loops, MHD turbulence in an expanding atmosphere, and hot mass transport in the solar active prominence.

Post-Flare Giant Arches - Unanswered Questions

NASA Astrophysics Data System (ADS)

West, M. J.; Seaton, D. B.; Dennis, B. R.; Palmerio, E.; Savage, S. L.

2017-12-01

Recent observations from the SWAP EUV imager on-board PROBA2 and SXI X-ray observations from the GOES satellite have shown that post-flare giant arches and regular post-flare loops are one and the same thing. However, it is still not clear how certain loop systems are able to sustain prolonged growth to heights greater than half a solar-radii. In this presentation we further explore the energy deposition rate above post-flare loop systems through high-energy RHESSI observations. We also explore the difference between the growth of different loop systems through an epoch analysis. The epoch analysis is initially performed over the period when the STEREO satellites were in quadrature with PROBA2 allowing us to assess the difference between their on-disk and on-limb signatures. Giant arches are generally characterised by their height of growth when observed close to the solar limb, but due to the optically thin nature of the EUV solar atmosphere, projection effects and the scarcity of events occurring within 5 degrees of the limb it is not understood how common these events are. Using the analysis during the quadrature period we gain a better understanding of how rare these events are, and by determining characteristic on disk signatures we can combine our data set with magnetogram observations to better understand their magnetic evolution.

? PID output-feedback control under event-triggered protocol

NASA Astrophysics Data System (ADS)

Zhao, Di; Wang, Zidong; Ding, Derui; Wei, Guoliang; Alsaadi, Fuad E.

2018-07-01

This paper is concerned with the ? proportional-integral-derivative (PID) output-feedback control problem for a class of linear discrete-time systems under event-triggered protocols. The controller and the actuators are connected through a communication network of limited bandwidth, and an event-triggered communication mechanism is adopted to decide when a certain control signal should be transmitted to the respective actuator. Furthermore, a novel PID output-feedback controller is designed where the accumulative sum-loop (the counterpart to the integral-loop in the continues-time setting) operates on a limited time-window with hope to mitigate the effect from the past measurement data. The main objective of the problem under consideration is to design a desired PID controller such that the closed-loop system is exponentially stable and the prescribed ? disturbance rejection attenuation level is guaranteed under event-triggered protocols. By means of the Lyapunov stability theory combined with the orthogonal decomposition, sufficient conditions are established under which the addressed PID controller design problem is recast into a linear convex optimization one that can be easily solved via available software packages. Finally, a simulation example is exploited to illustrate the usefulness and effectiveness of the established control scheme.

Model predictive control of P-time event graphs

NASA Astrophysics Data System (ADS)

Hamri, H.; Kara, R.; Amari, S.

2016-12-01

This paper deals with model predictive control of discrete event systems modelled by P-time event graphs. First, the model is obtained by using the dater evolution model written in the standard algebra. Then, for the control law, we used the finite-horizon model predictive control. For the closed-loop control, we used the infinite-horizon model predictive control (IH-MPC). The latter is an approach that calculates static feedback gains which allows the stability of the closed-loop system while respecting the constraints on the control vector. The problem of IH-MPC is formulated as a linear convex programming subject to a linear matrix inequality problem. Finally, the proposed methodology is applied to a transportation system.

First cytoplasmic loop of glucagon-like peptide-1 receptor can function at the third cytoplasmic loop position of rhodopsin.

PubMed

Yamashita, Takahiro; Tose, Koji; Shichida, Yoshinori

2008-01-01

G protein-coupled receptors (GPCRs) are classified into several families based on their amino acid sequences. In family 1, GPCRs such as rhodopsin and adrenergic receptor, the structure-function relationship has been extensively investigated to demonstrate that exposure of the third cytoplasmic loop is essential for selective G protein activation. In contrast, much less is known about other families. Here we prepared chimeric mutants between Gt-coupled rhodopsin and Gi/Go- and Gs-coupled glucagon-like peptide-1 (GLP-1) receptor of family 2 and tried to identify the loop region that functions at the third cytoplasmic loop position of rhodopsin. We succeeded in expressing a mutant having the first cytoplasmic loop of GLP-1 receptor and found that this mutant activated Gi and Go efficiently but did not activate Gt. Moreover, the rhodopsin mutant having the first loop of Gs-coupled secretin receptor of family 2 decreased the Gi and Go activation efficiencies. Therefore, the first loop of GLP-1 receptor would share a similar role to the third loop of rhodopsin in G protein activation. This result strongly suggested that different families of GPCRs have maintained molecular architectures of their ancestral types to generate a common mechanism, namely exposure of the cytoplasmic loop, to activate peripheral G protein.

Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion

PubMed Central

Duroc, Yann; Kumar, Rajeev; Ranjha, Lepakshi; Adam, Céline; Guérois, Raphaël; Md Muntaz, Khan; Marsolier-Kergoat, Marie-Claude; Dingli, Florent; Laureau, Raphaëlle; Loew, Damarys; Llorente, Bertrand; Charbonnier, Jean-Baptiste; Cejka, Petr; Borde, Valérie

2017-01-01

Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations. DOI: http://dx.doi.org/10.7554/eLife.21900.001 PMID:28051769

78 FR 34881 - Special Local Regulations; Marine Events, Wrightsville Channel; Wrightsville Beach, NC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

...-AA08 Special Local Regulations; Marine Events, Wrightsville Channel; Wrightsville Beach, NC AGENCY... Regulation for the ``Swim the Loop/Motts Channel Sprint'' swim event, to be held on the waters adjacent to... necessary to provide for the safety of life on navigable waters during the event. This action will restrict...

Microflaring in Low-Lying Core Fields and Extended Coronal Heating in the Quiet Sun

NASA Technical Reports Server (NTRS)

Porter, Jason G.; Falconer, D. A.; Moore, Ronald L.

1999-01-01

We have previously reported analyses of Yohkoh SXT data examining the relationship between the heating of extended coronal loops (both within and stemming from active regions) and microflaring in core fields lying along neutral lines near their footpoints (J. G. Porter, D. A. Falconer, and R. L. Moore 1998, in Solar Jets and Coronal Plumes, ed. T. Guyenne, ESA SP-421, and references therein). We found a surprisingly poor correlation of intensity variations in the extended loops with individual microflares in the compact heated areas at their feet, despite considerable circumstancial evidence linking the heating processes in these regions. Now, a study of Fe XII image sequences from SOHO EIT show that similar associations of core field structures with the footpoints of very extended coronal features can be found in the quiet Sun. The morphology is consistent with the finding of Wang et al. (1997, ApJ 484, L75) that polar plumes are rooted at sites of mixed polarity in the magnetic network. We find that the upstairs/downstairs intensity variations often follow the trend, identified in the active region observations, of a weak correspondence. Apparently much of the coronal heating in the extended loops is driven by a type of core field magnetic activity that is "cooler" than the events having the coronal signature of microflares, i.e., activity that results in little heating within the core fields themselves. This work was funded by the Solar Physics Branch of NASA's Office of Space Science through the SR&T Program and the SEC Guest Investigator Program.

Early evolution of an energetic coronal mass ejection and its relation to EUV waves

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

Liu, Rui; Wang, Yuming; Shen, Chenglong, E-mail: rliu@ustc.edu.cn

2014-12-10

We study a coronal mass ejection (CME) associated with an X-class flare whose initiation is clearly observed in the low corona with high-cadence, high-resolution EUV images, providing us a rare opportunity to witness the early evolution of an energetic CME in detail. The eruption starts with a slow expansion of cool overlying loops (∼1 MK) following a jet-like event in the periphery of the active region. Underneath the expanding loop system, a reverse S-shaped dimming is seen immediately above the brightening active region in hot EUV passbands. The dimming is associated with a rising diffuse arch (∼6 MK), which wemore » interpret as a preexistent, high-lying flux rope. This is followed by the arising of a double hot channel (∼10 MK) from the core of the active region. The higher structures rise earlier and faster than lower ones, with the leading front undergoing extremely rapid acceleration up to 35 km s{sup –2}. This suggests that the torus instability is the major eruption mechanism and that it is the high-lying flux rope rather than the hot channels that drives the eruption. The compression of coronal plasmas skirting and overlying the expanding loop system, whose aspect ratio h/r increases with time as a result of the rapid upward acceleration, plays a significant role in driving an outward-propagating global EUV wave and a sunward-propagating local EUV wave, respectively.« less

Enhanced activation of human T cell clones specific for virus-like particles expressing the HIV V3 loop in the presence of HIV V3 loop-specific polyclonal antibodies

PubMed Central

Peifang, S.; Pira, G. L.; Fenoglio, D.; Harris, S.; Costa, M. G.; Venturino, V.; Dessì, V.; Layton, G.; Laman, J.; Huisman, J. G.; Manca, F.

1994-01-01

Recombinant virus-like particles (VLP), formed by the yeast Ty p1 protein, carrying the HIV gp120 V3 loop on their surface (V3-VLP) have been tested in vitro for immunogenicity and antigenicity by using VLP p1-specific human CD4+ T cell lines and clones. VLP-specific human T cell lines and clones were generated from normal individuals, indicating that VLP-specific precursor cells present in the peripheral lymphocyte pool can be induced to expand clonally upon antigen challenge in vitro, in the absence of previous immunization. It was also shown that V3-specific polyclonal antibodies enhance V3-VLP-induced activation of VLP-specific T cell clones. Antibody-dependent potentiation has been shown previously in other antigen systems, and it depends on enhanced uptake of complexed antigen by Fc receptor-positive antigen-presenting cells. Since in this case antigen is internalized by presenting cells as a complex, it can be inferred that a similar event of antibody-mediated antigen uptake can take place with V3-specific B cells, resulting in presentation by the B cells of T helper epitopes derived from processing of the VLP p1 moiety. This suggests that T helper cells specific for the carrier VLP p1 protein can be activated to provide help to V3-specific B cells in the presence of the appropriate antigen construct. PMID:7915974

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

Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan

Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In thismore » study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.« less

Coronal loops and active region structure

NASA Technical Reports Server (NTRS)

Webb, D. F.; Zirin, H.

1981-01-01

Synoptic H-alpha Ca K, magnetograph and Skylab soft X-ray and EUV data were compared for the purpose of identifying the basic coronal magnetic structure of loops in a 'typical' active region and studying its evolution. A complex of activity in July 1973, especially McMath 12417, was emphasized. The principal results are: (1) most of the brightest loops connected the bright f plage to either the sunspot penumbra or to p satellite spots; no non-flaring X-ray loops end in umbrae; (2) short, bright loops had one or both ends in regions of emergent flux, strong field or high field gradients; (3) stable, strongly sheared loop arcades formed over filaments; (4) EFRs were always associated with compact X-ray arcades; and (5) loops connecting to other active regions had their bases in outlying plage of weak field strength in McM 417 where H-alpha fibrils marked the direction of the loops

Locking the Active Conformation of c-Src Kinase through the Phosphorylation of the Activation Loop

PubMed Central

Meng, Yilin; Roux, Benoît

2013-01-01

Molecular dynamics umbrella sampling simulations are used to compare the relative stability of the active conformation of the catalytic domain of c-Src kinase while the tyrosine 416 in the activation loop (A-loop) is either unphosphorylated or phosphorylated. When the A-loop is unphosphorylated, there is considerable flexiblity of the kinase. While the active conformation of the kinase is not forbidden and can be visited transiently, it is not the predominant state. This is consistent with the view that c-Src displays some catalytic activity even when the A-loop is unphosphorylated. In contrast, phosphorylation of the A-loop contributes to stabilize several structural features that are critical for catalysis, such as the hydrophobic regulatory spine, the HRD motif, and the electrostatic switch. In summary, the free energy landscape calculations demonstrate that phosphorylation of tyrosine 416 in the A-loop essentially “locks” the kinase into its catalytically competent conformation. PMID:24103328

Interlocked positive and negative feedback network motifs regulate β-catenin activity in the adherens junction pathway

PubMed Central

Klinke, David J.; Horvath, Nicholas; Cuppett, Vanessa; Wu, Yueting; Deng, Wentao; Kanj, Rania

2015-01-01

The integrity of epithelial tissue architecture is maintained through adherens junctions that are created through extracellular homotypic protein–protein interactions between cadherin molecules. Cadherins also provide an intracellular scaffold for the formation of a multiprotein complex that contains signaling proteins, including β-catenin. Environmental factors and controlled tissue reorganization disrupt adherens junctions by cleaving the extracellular binding domain and initiating a series of transcriptional events that aim to restore tissue homeostasis. However, it remains unclear how alterations in cell adhesion coordinate transcriptional events, including those mediated by β-catenin in this pathway. Here were used quantitative single-cell and population-level in vitro assays to quantify the endogenous pathway dynamics after the proteolytic disruption of the adherens junctions. Using prior knowledge of isolated elements of the overall network, we interpreted these data using in silico model-based inference to identify the topology of the regulatory network. Collectively the data suggest that the regulatory network contains interlocked network motifs consisting of a positive feedback loop, which is used to restore the integrity of adherens junctions, and a negative feedback loop, which is used to limit β-catenin–induced gene expression. PMID:26224311

Inflows in the Inner White-light Corona: The Closing-down of Flux after Coronal Mass Ejections

NASA Astrophysics Data System (ADS)

Hess, P.; Wang, Y.-M.

2017-11-01

During times of high solar activity, the Solar and Heliospheric Observatory/Large Angle and Spectrometric Coronagraph C2 coronagraph has recorded multitudes of small features moving inward through its 2{--}6 {R}⊙ field of view. These outer-coronal inflows, which are concentrated around the heliospheric current sheet, tend to be poorly correlated with individual coronal mass ejection (CME) events. Using running-difference movies constructed from Solar Terrestrial Relations Observatory/COR1 coronagraph images taken during 2008-2014, we have identified large numbers of inward-moving features at heliocentric distances below 2 {R}⊙ , with the rate increasing with sunspot and CME activity. Most of these inner-coronal inflows are closely associated with CMEs, being observed during and in the days immediately following the eruptions. Here, we describe several examples of the pinching-off of tapered streamer structures in the wake of CMEs. This type of inflow event is characterized by a separation of the flow into incoming and outgoing components connected by a thin spike, which is interpreted as a continually elongating current sheet viewed edge-on; by the prior convergence of narrow rays toward the current sheet; and by a succession of collapsing loops that form a cusp-shaped structure at the base of the current sheet. The re-forming streamer overlies a growing post-eruption arcade that is visible in EUV images. These observations provide support for standard reconnection models for the formation/evolution of flux ropes during solar eruptive events. We suggest that inflow streams that occur over a relatively wide range of position angles result from the pinching-off of loop arcades whose axes are oriented parallel rather than perpendicular to the sky plane.

Hot spine loops and the nature of a late-phase solar flare

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

Sun, Xudong; Todd Hoeksema, J.; Liu, Yang

2013-12-01

The fan-spine magnetic topology is believed to be responsible for many curious features in solar explosive events. A spine field line links distinct flux domains, but direct observation of such a feature has been rare. Here we report a unique event observed by the Solar Dynamic Observatory where a set of hot coronal loops (over 10 MK) connected to a quasi-circular chromospheric ribbon at one end and a remote brightening at the other. Magnetic field extrapolation suggests that these loops are partly tracers of the evolving spine field line. Continuous slipping- and null-point-type reconnections were likely at work, energizing themore » loop plasma and transferring magnetic flux within and across the fan quasi-separatrix layer. We argue that the initial reconnection is of the 'breakout' type, which then transitioned to a more violent flare reconnection with an eruption from the fan dome. Significant magnetic field changes are expected and indeed ensued. This event also features an extreme-ultraviolet (EUV) late phase, i.e., a delayed secondary emission peak in warm EUV lines (about 2-7 MK). We show that this peak comes from the cooling of large post-reconnection loops beside and above the compact fan, a direct product of eruption in such topological settings. The long cooling time of the large arcades contributes to the long delay; additional heating may also be required. Our result demonstrates the critical nature of cross-scale magnetic coupling—topological change in a sub-system may lead to explosions on a much larger scale.« less

ORION Environmental Control and Life Support Systems Suit Loop and Pressure Control Analysis

NASA Technical Reports Server (NTRS)

Eckhardt, Brad; Conger, Bruce; Stambaugh, Imelda C.

2015-01-01

Under NASA's ORION Multi-Purpose Crew Vehicle (MPCV) Environmental Control and Life Support System (ECLSS) Project at Johnson Space Center's (JSC), the Crew and Thermal Systems Division has developed performance models of the air system using Thermal Desktop/FloCAD. The Thermal Desktop model includes an Air Revitalization System (ARS Loop), a Suit Loop, a Cabin Loop, and Pressure Control System (PCS) for supplying make-up gas (N2 and O2) to the Cabin and Suit Loop. The ARS and PCS are designed to maintain air quality at acceptable O2, CO2 and humidity levels as well as internal pressures in the vehicle Cabin and during suited operations. This effort required development of a suite of Thermal Desktop Orion ECLSS models to address the need for various simulation capabilities regarding ECLSS performance. An initial highly detailed model of the ARS Loop was developed in order to simulate rapid pressure transients (water hammer effects) within the ARS Loop caused by events such as cycling of the Pressurized Swing Adsorption (PSA) Beds and required high temporal resolution (small time steps) in the model during simulation. A second ECLSS model was developed to simulate events which occur over longer periods of time (over 30 minutes) where O2, CO2 and humidity levels, as well as internal pressures needed to be monitored in the cabin and for suited operations. Stand-alone models of the PCS and the Negative Pressure relief Valve (NPRV) were developed to study thermal effects within the PCS during emergency scenarios (Cabin Leak) and cabin pressurization during vehicle re-entry into Earth's atmosphere. Results from the Orion ECLSS models were used during Orion Delta-PDR (July, 2014) to address Key Design Requirements (KDR's) for Suit Loop operations for multiple mission scenarios.

Modelling nanoflares in active regions and implications for coronal heating mechanisms

PubMed Central

Cargill, P. J.; Warren, H. P.; Bradshaw, S. J.

2015-01-01

Recent observations from the Hinode and Solar Dynamics Observatory spacecraft have provided major advances in understanding the heating of solar active regions (ARs). For ARs comprising many magnetic strands or sub-loops heated by small, impulsive events (nanoflares), it is suggested that (i) the time between individual nanoflares in a magnetic strand is 500–2000 s, (ii) a weak ‘hot’ component (more than 106.6 K) is present, and (iii) nanoflare energies may be as low as a few 1023 ergs. These imply small heating events in a stressed coronal magnetic field, where the time between individual nanoflares on a strand is of order the cooling time. Modelling suggests that the observed properties are incompatible with nanoflare models that require long energy build-up (over 10 s of thousands of seconds) and with steady heating. PMID:25897093

Phototropism: translating light into directional growth.

PubMed

Hohm, Tim; Preuten, Tobias; Fankhauser, Christian

2013-01-01

Phototropism allows plants to align their photosynthetic tissues with incoming light. The direction of incident light is sensed by the phototropin family of blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light-activated protein kinases. The kinase activity of phototropins and phosphorylation of residues in the activation loop of their kinase domains are essential for the phototropic response. These initial steps trigger the formation of the auxin gradient across the hypocotyl that leads to asymmetric growth. The molecular events between photoreceptor activation and the growth response are only starting to be elucidated. In this review, we discuss the major steps leading from light perception to directional growth concentrating on Arabidopsis. In addition, we highlight links that connect these different steps enabling the phototropic response.

Generic absence of strong singularities in loop quantum Bianchi-IX spacetimes

NASA Astrophysics Data System (ADS)

Saini, Sahil; Singh, Parampreet

2018-03-01

We study the generic resolution of strong singularities in loop quantized effective Bianchi-IX spacetime in two different quantizations—the connection operator based ‘A’ quantization and the extrinsic curvature based ‘K’ quantization. We show that in the effective spacetime description with arbitrary matter content, it is necessary to include inverse triad corrections to resolve all the strong singularities in the ‘A’ quantization. Whereas in the ‘K’ quantization these results can be obtained without including inverse triad corrections. Under these conditions, the energy density, expansion and shear scalars for both of the quantization prescriptions are bounded. Notably, both the quantizations can result in potentially curvature divergent events if matter content allows divergences in the partial derivatives of the energy density with respect to the triad variables at a finite energy density. Such events are found to be weak curvature singularities beyond which geodesics can be extended in the effective spacetime. Our results show that all potential strong curvature singularities of the classical theory are forbidden in Bianchi-IX spacetime in loop quantum cosmology and geodesic evolution never breaks down for such events.

Dynamical and Physical Properties of a Post-Coronal Mass Ejection Current Sheet

NASA Technical Reports Server (NTRS)

Ko, Yuan-Kuen; Raymond, John C.; Lin, Jun; Lawrence, Gareth; Li, Jing; Fludra, Andrzej

2003-01-01

In the eruptive process of the Kopp-Pneuman type, the closed magnetic field is stretched by the eruption so much that it is usually believed to be " open " to infinity. Formation of the current sheet in such a configuration makes it possible for the energy in the coronal magnetic field to quickly convert into thermal and kinetic energies and cause significant observational consequences, such as growing postflare/CME loop system in the corona, separating bright flare ribbons in the chromosphere, and fast ejections of the plasma and the magnetic flux. An eruption on 2002 January 8 provides us a good opportunity to look into these observational signatures of and place constraints on the theories of eruptions. The event started with the expansion of a magnetic arcade over an active region, developed into a coronal mass ejection (CME), and left some thin streamer-like structures with successively growing loop systems beneath them. The plasma outflow and the highly ionized states of the plasma inside these streamer-like structures, as well as the growing loops beneath them, lead us to conclude that these structures are associated with a magnetic reconnection site, namely, the current sheet, of this eruptive process. We combine the data from the Ultraviolet Coronagraph Spectrometer, Large Angle and Spectrometric Coronagraph Experiment, EUV Imaging Telescope, and Coronal Diagnostic Spectrometer on board the Solar and Heliospheric Observatory, as well is from the Mauna Loa Solar Observatory Mark IV K-coronameter, to investigate the morphological and dynamical properties of this event, as well as the physical properties of the current sheet. The velocity and acceleration of the CME reached up to 1800 km/s and 1 km/sq s, respectively. The acceleration is found to occur mainly at the lower corona (<2.76 Solar Radius). The post-CME loop systems showed behaviors of both postflare loops (upward motion with decreasing speed) and soft X-ray giant arches (upward motion with constant speed, or acceleration) according to the definition of Svestka. In the current sheet, the presence of highly ionized ions, such as Fe(+17) and Ca(+13), suggests temperature as high as (3-4) x 10(exp 6) K, and the plasma outflows have speeds ranging from 300 to 650 km/s. Absolute elemental abundances in the current sheet show a strong first ionization potential effect and have values similar to those found in the active region streamers. The magnetic field strength in the vicinity of the current sheet is found to be of the order of 1 G.

Thermal Analysis of Post-eruption Loops from 80,000 to 1.6 million K

NASA Technical Reports Server (NTRS)

Kucera, T.; Landi, E.

2006-01-01

We analyze the thermal properties of a set of post eruptive loops which appeared after a prominence eruption on April 30, 2004. The event was observed by TRACE and SOHO/SUMER. The SUMER data was taken from a single slit location with a 90 second cadence and included a number of lines spanning the temperature range 80,000 to 1.6 million K. We perform a differential emission measure analysis of the loops in order to study their thermal evolution.

A gigantic coronal jet ejected from a compact active region in a coronal hole

NASA Technical Reports Server (NTRS)

Shibata, K.; Nitta, N.; Strong, K. T.; Matsumoto, R.; Yokoyama, T.; Hirayama, T.; Hudson, H.; Ogawara, Y.

1994-01-01

A gigantic coronal jet greater than 3 x 10(exp 5) km long (nearly half the solar radius) has been found with the soft X-ray telescope (SXT) on board the solar X-ray satellite, Yohkoh. The jet was ejected on 1992 January 11 from an 'anemone-type' active region (AR) appearing in a coronal hole and is one of the largest coronal X-ray jets observed so far by SXT. This gigantic jet is the best observed example of many other smaller X-ray jets, because the spatial structures of both the jet and the AR located at its base are more easily resolved. The range of apparent translational velocities of the bulk of the jet was between 90 and 240 km s(exp -1), with the corresponding kinetic energy estimated to be of order of 10(exp 28) ergs. A detailed analysis reveals that the jet was associated with a loop brightening (a small flare) that occurred in the active region. Several features of this observation suggest and are consistent with a magnetic reconnection mechanism for the production of such a 'jet-loop-brightening' event.

Electron acceleration in connection with radio noise storm onsets or enhancements

NASA Astrophysics Data System (ADS)

Vilmer, N.; Trottet, G.

2008-11-01

Radio noise storms are generated by suprathermal (≃ 10 keV) electrons accelerated continuously over time scales of hours or days in active region magnetic fields. They are related to emerging magnetic loops interacting with overlying loops and leading to magnetic coronal reconfiguration (e.g. Bentley et al. 2000). Noise storm onsets or enhancements have been sometimes observed in association with a flare-like sudden energy release in the active region producing a localized microwave (Raulin et al. 1991) or soft X-ray brightening (Raulin & Klein 1994). A few cases have also been reported in which 10-30 keV emission from a superhot plasma or from non-thermal electrons have been observed at the onset of noise storms (Crosby et al. 1996) confirming that a flare-like energy release in the lower corona could be a necessary condition for noise storms to start. No spatially resolved hard X-ray observations were however available in the case of the latter analysis, allowing to check that the flare-like emission and the noise storm were originating from the same active region. We present here an event for which both radio and hard X-ray (HXR) spatially resolved observations are available.

Joint NuSTAR and IRIS observation of a microflaring active region

NASA Astrophysics Data System (ADS)

Hannah, I. G.; Kleint, L.; Krucker, S.; Glesener, L.; Grefenstette, B.

2017-12-01

We present observations of a weakly microflaring active region observed in X-rays with NuSTAR, UV with IRIS and EUV with SDO/AIA. NuSTAR was pointed at this unnamed active region near the East limb between 23:27UT and 23:37UT 26-July-2016, finding mostly quiescent emission except for a small microflare about 23:35UT. The NuSTAR spectrum for the pre-microflare time (23:27UT to 23:34UT) is well fitted by a single thermal component of about 3MK and combined with SDO/AIA we can determine the differential emission measure (DEM), finding it, as expected, drops very sharply to higher temperatures. During the subsequent microflare, the increase in NuSTAR counts matches a little brightening loop observed with IRIS SJI 1400Å and SDO/AIA. Fortuitously the IRIS slit crosses this microflaring loop and we find an increased emission in Si IV 1394Å, Si IV 1403Å and O IV 1402Å but only average line widths and velocities. The NuSTAR microflare spectrum shows heating to higher temperatures and also allows us to investigate the energetics of this event.

Seismic &Infrasound Integrated Array "Apatity". Techniques, data processing, first results of observations.

NASA Astrophysics Data System (ADS)

Vinogradov, Y.; Baryshnikov, A.

2003-04-01

Since September 2001 3 infrasound membrane type sensors "K-304 AM" have been installed on the territory seismic array "Apatity" near the lake Imandra. A seismic array comprising 11 short-period sensors (type "Geotech S-500"), disposed on small and large circle (0.4 and 1 km diameter). Infrasound sensors located on small circle near the seismograths. All data are digitized at the array site and transmitted in real time to a processing center in Apatity to the Kola Regional Seismological Centre (KRSC). Common complex we are called - Seismic &Infrasound Integrated Array (SISIA) "Apatity". To support temporary storage the transmitting data in a disk loop and access to the data "NEWNORAC" program was created. This program replaced "NORAC" system developed by Norwegian Institute NORSAR, which was in use in KRSC before. A program package EL (event locator) for display and processing of the data has been modified. Now it includes the following : - quick access to the data stored in the disk loop (last two weeks); - data convertation from disk loop format to CSS 3.0 format; - data filtering using bandpass, highpass, lowpass, adaptive or rejector filters; - calculation of spectra and sonograms (spectral diagrams); - seismic events location with plotting on a map; - calculation of backazimuth and apparent velocity of acoustic wave by similar parts of wave recordings; - loading and processing CSS 3.0 seismic and acoustic data from KRSC archive. To store the acoustic data permanently the program BARCSS was made. It rewrites the data from the disk loop to KRSC archive in CSS 3.0 format. For comparison of acoustic noise level with wind we use data from meteorological station in Kandalaksha city, sampling rate is 3 hours. During the period from October 2001 to October 2002 more than 745 seismic events, which basically connected with mine technical activity of the large mining enterprises at the Kola Peninsula, were registered. The most part of events, caused by ground explosions, was registered by infrasound part of SISIA "Apatity". Their sources were at distances from 38 to 220 km. The result of observations during the first 1 year enabled us to estimate frequency range and main directions of arrivals of acoustic waves and noise level in the place of observations. In accordance with the results and relief a 4-rays wind-noise-reducing pipe array would be install at all 3 sensors at May 2003, for improvement the delectability during windy conditions. A schemes of the SISIA "Apatity", data transmitting and processing and samples of detected signals are shown in the presentation.

Auditory event perception: the source-perception loop for posture in human gait.

PubMed

Pastore, Richard E; Flint, Jesse D; Gaston, Jeremy R; Solomon, Matthew J

2008-01-01

There is a small but growing literature on the perception of natural acoustic events, but few attempts have been made to investigate complex sounds not systematically controlled within a laboratory setting. The present study investigates listeners' ability to make judgments about the posture (upright-stooped) of the walker who generated acoustic stimuli contrasted on each trial. We use a comprehensive three-stage approach to event perception, in which we develop a solid understanding of the source event and its sound properties, as well as the relationships between these two event stages. Developing this understanding helps both to identify the limitations of common statistical procedures and to develop effective new procedures for investigating not only the two information stages above, but also the decision strategies employed by listeners in making source judgments from sound. The result is a comprehensive, ultimately logical, but not necessarily expected picture of both the source-sound-perception loop and the utility of alternative research tools.

Brain network dynamics in the human articulatory loop.

PubMed

Nishida, Masaaki; Korzeniewska, Anna; Crone, Nathan E; Toyoda, Goichiro; Nakai, Yasuo; Ofen, Noa; Brown, Erik C; Asano, Eishi

2017-08-01

The articulatory loop is a fundamental component of language function, involved in the short-term buffer of auditory information followed by its vocal reproduction. We characterized the network dynamics of the human articulatory loop, using invasive recording and stimulation. We measured high-gamma activity 70-110 Hz recorded intracranially when patients with epilepsy either only listened to, or listened to and then reproduced two successive tones by humming. We also conducted network analyses, and analyzed behavioral responses to cortical stimulation. Presentation of the initial tone elicited high-gamma augmentation bilaterally in the superior-temporal gyrus (STG) within 40ms, and in the precentral and inferior-frontal gyri (PCG and IFG) within 160ms after sound onset. During presentation of the second tone, high-gamma augmentation was reduced in STG but enhanced in IFG. The task requiring tone reproduction further enhanced high-gamma augmentation in PCG during and after sound presentation. Event-related causality (ERC) analysis revealed dominant flows within STG immediately after sound onset, followed by reciprocal interactions involving PCG and IFG. Measurement of cortico-cortical evoked-potentials (CCEPs) confirmed connectivity between distant high-gamma sites in the articulatory loop. High-frequency stimulation of precentral high-gamma sites in either hemisphere induced speech arrest, inability to control vocalization, or forced vocalization. Vocalization of tones was accompanied by high-gamma augmentation over larger extents of PCG. Bilateral PCG rapidly and directly receives feed-forward signals from STG, and may promptly initiate motor planning including sub-vocal rehearsal for short-term buffering of auditory stimuli. Enhanced high-gamma augmentation in IFG during presentation of the second tone may reflect high-order processing of the tone sequence. The articulatory loop employs sustained reciprocal propagation of neural activity across a network of cortical sites with strong neurophysiological connectivity. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Upper-Airway Collapsibility and Loop Gain Predict the Response to Oral Appliance Therapy in Patients with Obstructive Sleep Apnea

PubMed Central

Andara, Christopher; Landry, Shane; Sands, Scott A.; Joosten, Simon A.; Owens, Robert L.; White, David P.; Hamilton, Garun S.; Wellman, Andrew

2016-01-01

Rationale: Oral appliances (OAs) are commonly used as an alternative treatment to continuous positive airway pressure for patients with obstructive sleep apnea (OSA). However, OAs have variable success at reducing the apnea–hypopnea index (AHI), and predicting responders is challenging. Understanding this variability may lie with the recognition that OSA is a multifactorial disorder and that OAs may affect more than just upper-airway anatomy/collapsibility. Objectives: The objectives of this study were to determine how OA alters AHI and four phenotypic traits (upper-airway anatomy/collapsibility and muscle function, loop gain, and arousal threshold), and baseline predictors of which patients gain the greatest benefit from therapy. Methods: In a randomized crossover study, 14 patients with OSA attended two sleep studies with and without their OA. Under each condition, AHI and the phenotypic traits were assessed. Multiple linear regression was used to determine independent predictors of the reduction in AHI. Measurements and Main Results: OA therapy reduced the AHI (30 ± 5 vs. 11 ± 2 events/h; P < 0.05), which was driven by improvements in upper-airway anatomy/collapsibility under passive (1.9 ± 0.7 vs. 4.7 ± 0.6 L/min; P < 0.005) and active conditions (2.4 ± 0.9 vs. 6.2 ± 0.4 L/min; P < 0.001). No changes were seen in muscle function, loop gain, or the arousal threshold. Using multivariate analysis, baseline passive upper-airway collapsibility and loop gain were independent predictors of the reduction in AHI (r2 = 0.70; P = 0.001). Conclusions: Our findings suggest that OA therapy improves the upper-airway collapsibility under passive and active conditions. Importantly, a greater response to therapy occurred in those patients with a mild anatomic compromise and a lower loop gain. PMID:27181367

Positive And Negative Feedback Loops Coupled By Common Transcription Activator And Repressor

NASA Astrophysics Data System (ADS)

Sielewiesiuk, Jan; Łopaciuk, Agata

2015-03-01

Dynamical systems consisting of two interlocked loops with negative and positive feedback have been studied using the linear analysis of stability and numerical solutions. Conditions for saddle-node bifurcation were formulated in a general form. Conditions for Hopf bifurcations were found in a few symmetrical cases. Auto-oscillations, when they exist, are generated by the negative feedback repressive loop. This loop determines the frequency and amplitude of oscillations. The positive feedback loop of activation slightly modifies the oscillations. Oscillations are possible when the difference between Hilll's coefficients of the repression and activation is sufficiently high. The highly cooperative activation loop with a fast turnover slows down or even makes the oscillations impossible. The system under consideration can constitute a component of epigenetic or enzymatic regulation network.

Kinin-B2 receptor expression and activity during differentiation of embryonic rat neurospheres.

PubMed

Martins, Antonio H; Alves, Janaína M; Trujillo, Cleber A; Schwindt, Telma T; Barnabé, Gabriela F; Motta, Fabiana L T; Guimaraes, Alessander O; Casarini, Dulce E; Mello, Luiz E; Pesquero, João B; Ulrich, Henning

2008-04-01

Neural progenitor cells were isolated from rat fetal telencephalon and proliferate as neurospheres in the presence of EGF, FGF-2, and heparin. In the absence of these growth factors, neurospheres differentiate into neurons, astrocytes, and oligodendrocytes. Using an embryonal carcinoma cell line as in vitro differentiation model, we have already demonstrated the presence of an autocrine loop system between kinin-B2 receptor activity and secretion of its ligand bradykinin (BK) as prerequisites for final neuronal differentiation (Martins et al., J Biol Chem 2005; 280: 19576-19586). The aim of this study was to verify the activity of the kallikrein-kinin system (KKS) during neural progenitor cell differentiation. Immunofluorescence studies and flow cytometry analysis revealed increases in glial fibrillary acidic protein and beta-3 tubulin expression and decrease in the number of nestin-positive cells along neurospheres differentiation, indicating the transition of neural progenitor cells to astrocytes and neurons. Kinin-B2 receptor expression and activity, secretion of BK into the medium, and presence of high-molecular weight kininogen suggest the participation of the KKS in neurosphere differentiation. Functional kinin-B2 receptors and BK secretion indicate an autocrine loop during neurosphere differentiation to neurons, astrocytes, and oligodendrocytes, reflecting events occurring during early brain development. (c) 2008 International Society for Analytical Cytology.

CIFAR10-DVS: An Event-Stream Dataset for Object Classification

PubMed Central

Li, Hongmin; Liu, Hanchao; Ji, Xiangyang; Li, Guoqi; Shi, Luping

2017-01-01

Neuromorphic vision research requires high-quality and appropriately challenging event-stream datasets to support continuous improvement of algorithms and methods. However, creating event-stream datasets is a time-consuming task, which needs to be recorded using the neuromorphic cameras. Currently, there are limited event-stream datasets available. In this work, by utilizing the popular computer vision dataset CIFAR-10, we converted 10,000 frame-based images into 10,000 event streams using a dynamic vision sensor (DVS), providing an event-stream dataset of intermediate difficulty in 10 different classes, named as “CIFAR10-DVS.” The conversion of event-stream dataset was implemented by a repeated closed-loop smooth (RCLS) movement of frame-based images. Unlike the conversion of frame-based images by moving the camera, the image movement is more realistic in respect of its practical applications. The repeated closed-loop image movement generates rich local intensity changes in continuous time which are quantized by each pixel of the DVS camera to generate events. Furthermore, a performance benchmark in event-driven object classification is provided based on state-of-the-art classification algorithms. This work provides a large event-stream dataset and an initial benchmark for comparison, which may boost algorithm developments in even-driven pattern recognition and object classification. PMID:28611582

CIFAR10-DVS: An Event-Stream Dataset for Object Classification.

PubMed

Li, Hongmin; Liu, Hanchao; Ji, Xiangyang; Li, Guoqi; Shi, Luping

2017-01-01

Neuromorphic vision research requires high-quality and appropriately challenging event-stream datasets to support continuous improvement of algorithms and methods. However, creating event-stream datasets is a time-consuming task, which needs to be recorded using the neuromorphic cameras. Currently, there are limited event-stream datasets available. In this work, by utilizing the popular computer vision dataset CIFAR-10, we converted 10,000 frame-based images into 10,000 event streams using a dynamic vision sensor (DVS), providing an event-stream dataset of intermediate difficulty in 10 different classes, named as "CIFAR10-DVS." The conversion of event-stream dataset was implemented by a repeated closed-loop smooth (RCLS) movement of frame-based images. Unlike the conversion of frame-based images by moving the camera, the image movement is more realistic in respect of its practical applications. The repeated closed-loop image movement generates rich local intensity changes in continuous time which are quantized by each pixel of the DVS camera to generate events. Furthermore, a performance benchmark in event-driven object classification is provided based on state-of-the-art classification algorithms. This work provides a large event-stream dataset and an initial benchmark for comparison, which may boost algorithm developments in even-driven pattern recognition and object classification.

Observations of the Formation, Development, and Structure of a Current Sheet in an Eruptive Solar Flare

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

Seaton, Daniel B.; Darnel, Jonathan M.; Bartz, Allison E., E-mail: daniel.seaton@noaa.gov

2017-02-01

We present Atmospheric Imaging Assembly observations of a structure we interpret as a current sheet associated with an X4.9 flare and coronal mass ejection that occurred on 2014 February 25 in NOAA Active Region 11990. We characterize the properties of the current sheet, finding that the sheet remains on the order of a few thousand kilometers thick for much of the duration of the event and that its temperature generally ranged between 8 and 10 MK. We also note the presence of other phenomena believed to be associated with magnetic reconnection in current sheets, including supra-arcade downflows and shrinking loops.more » We estimate that the rate of reconnection during the event was M{sub A} ≈ 0.004–0.007, a value consistent with model predictions. We conclude with a discussion of the implications of this event for reconnection-based eruption models.« less

Skylab observations of X-ray loops connecting separate active regions. [solar activity

NASA Technical Reports Server (NTRS)

Chase, R. C.; Krieger, A. S.; Svestka, Z.; Vaiana, G. S.

1976-01-01

One hundred loops interconnecting 94 separate active solar regions detectable in soft X-rays were identified during the Skylab mission. While close active regions are commonly interconnected with loops, the number of such interconnections decreases steeply for longer distances; the longest interconnecting loop observed in the Skylab data connected regions separated by 37 deg. Several arguments are presented which support the point of view that this is the actual limit of the size of magnetic interconnections between active regions. No sympathetic flares could be found in the interconnected regions. These results cast doubt on the hypothesis that accelerated particles can be guided in interconnecting loops from one active region to another over distances of 100 deg or more and eventually produce sympathetic flares in them.

Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops.

PubMed

Kar, Anirban; Willcox, Smaranda; Griffith, Jack D

2016-11-02

The formation of DNA loops at chromosome ends (t-loops) and the transcription of telomeres producing G-rich RNA (TERRA) represent two central features of telomeres. To explore a possible link between them we employed artificial human telomeres containing long arrays of TTAGGG repeats flanked by the T7 or T3 promoters. Transcription of these DNAs generates a high frequency of t-loops within individual molecules and homologous recombination events between different DNAs at their telomeric sequences. T-loop formation does not require a single strand overhang, arguing that both terminal strands insert into the preceding duplex. The loops are very stable and some RNase H resistant TERRA remains at the t-loop, likely adding to their stability. Transcription of DNAs containing TTAGTG or TGAGTG repeats showed greatly reduced loop formation. While in the cell multiple pathways may lead to t-loop formation, the pathway revealed here does not depend on the shelterins but rather on the unique character of telomeric DNA when it is opened for transcription. Hence, telomeric sequences may have evolved to facilitate their ability to loop back on themselves. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effectiveness and safety of remote monitoring of patients with an implantable loop recorder.

PubMed

Drak-Hernández, Yasmín; Toquero-Ramos, Jorge; Fernández, José M; Pérez-Pereira, Elena; Castro-Urda, Víctor; Fernández-Lozano, Ignacio

2013-12-01

Implantable loop recorders have proven efficacy in the study of patients with syncope and palpitations. Remote monitoring of patients with pacemakers and implantable cardioverter-defibrillators has been shown to be safe and effective. The purpose of this study was to analyze the safety and effectiveness of remote monitoring in patients with an implantable loop recorder. Retrospective observational study in which 109 patients with an implantable loop recorder were analyzed and 2 population groups were compared: 1 receiving conventional follow-up consisting of 3-monthly office visits (41 patients) and 1 with remote monitoring via monthly telephone transmissions and yearly visits (68 patients). The mean follow-up was 64 weeks (range, 0.57-164.57 weeks). The study analyzed diagnosis of a significant event, defined as any event that led to a therapeutic approach and explained the symptoms leading to the implant, as well as the mean time from implant to diagnosis and the specific treatment. A significant event was diagnosed in 82.6% of patients; of these, 54.4% had a normal electrocardiogram; 26.7%, asystole; 15.6%, tachycardia, and 3.3%, bradycardia. The mean time from implant to diagnosis was 260 days (range, 5-947 days) in conventional follow-up, compared with 56 days (range, 0-650 days) in patients with remote monitoring (P<.01), which led to targeted treatment in this group 187 days earlier, on average, with no secondary complications. Remote monitoring of patients with an implantable loop recorder can significantly shorten the time to diagnosis and targeted treatment, without adversely affecting patient safety. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Neuromuscular control and ankle instability.

PubMed

Gutierrez, Gregory M; Kaminski, Thomas W; Douex, Al T

2009-04-01

Lateral ankle sprains (LAS) are common injuries in athletics and daily activity. Although most are resolved with conservative treatment, others develop chronic ankle instability (AI)-a condition associated with persistent pain, weakness, and instability-both mechanical (such as ligamentous laxity) and functional (neuromuscular impairment with or without mechanical laxity). The predominant theory in AI is one of articular deafferentation from the injury, affecting closed-loop (feedback/reflexive) neuromuscular control, but recent research has called that theory into question. A considerable amount of attention has been directed toward understanding the underlying causes of this pathology; however, little is known concerning the neuromuscular mechanisms behind the development of AI. The purpose of this review is to summarize the available literature on neuromuscular control in uninjured individuals and individuals with AI. Based on available research and reasonable speculation, it seems that open-loop (feedforward/anticipatory) neuromuscular control may be more important for the maintenance of dynamic joint stability than closed-loop control systems that rely primarily on proprioception. Therefore, incorporating perturbation activities into patient rehabilitation schemes may be of some benefit in enhancing these open-loop control mechanisms. Despite the amount of research conducted in this area, analysis of individuals with AI during dynamic conditions is limited. Future work should aim to evaluate dynamic perturbations in individuals with AI, as well as subjects who have a history of at least one LAS and never experienced recurrent symptoms. These potential findings may help elucidate some compensatory mechanisms, or more appropriate neuromuscular control strategies after an LAS event, thus laying the groundwork for future intervention studies that can attempt to reduce the incidence and severity of acute and chronic lateral ankle injury.

NON-POTENTIAL FIELDS IN THE QUIET SUN NETWORK: EXTREME-ULTRAVIOLET AND MAGNETIC FOOTPOINT OBSERVATIONS

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

Chesny, D. L.; Oluseyi, H. M.; Orange, N. B.

The quiet Sun (QS) magnetic network is known to contain dynamics which are indicative of non-potential fields. Non-potential magnetic fields forming ''S-shaped'' loop arcades can lead to the breakdown of static activity and have only been observed in high temperature X-ray coronal structures—some of which show eruptive behavior. Thus, analysis of this type of atmospheric structuring has been restricted to large-scale coronal fields. Here we provide the first identification of non-potential loop arcades exclusive to the QS supergranulation network. High-resolution Atmospheric Imaging Assembly data from the Solar Dynamics Observatory have allowed for the first observations of fine-scale ''S-shaped'' loop arcadesmore » spanning the network. We have investigated the magnetic footpoint flux evolution of these arcades from Heliospheric and Magnetic Imager data and find evidence of evolving footpoint flux imbalances accompanying the formation of these non-potential fields. The existence of such non-potentiality confirms that magnetic field dynamics leading to the build up of helicity exist at small scales. QS non-potentiality also suggests a self-similar formation process between the QS network and high temperature corona and the existence of self-organized criticality (SOC) in the form of loop-pair reconnection and helicity dissipation. We argue that this type of behavior could lead to eruptive forms of SOC as seen in active region (AR) and X-ray sigmoids if sufficient free magnetic energy is available. QS magnetic network dynamics may be considered as a coronal proxy at supergranular scales, and events confined to the network can even mimic those in coronal ARs.« less

New Aspects of a Lid-Removal Mechanism in the Onset of a SEP-Producing Eruption Sequence

NASA Technical Reports Server (NTRS)

Sterling, Alphonse C.; Moore, Ronald L.; Falconer, David A.; Knox, Javon M.

2014-01-01

We examine a sequence of two ejective eruptions from a single active region on 2012 January 23, using magnetograms and EUV images from SDO/HMI and SDO/AIA, and EUV images from STEREO. Cheng et al. (2013) showed that the first eruption's ("Eruption 1'') flux rope was apparent only in "hotter'' AIA channels, and that it removed overlying field that allowed the second eruption (``Eruption 2'') to begin via ideal MHD instability; here we say Eruption 2 began via a ``lid removal'' mechanism. We show that during Eruption-1's onset, its flux rope underwent ``tether weakening'' (TW) reconnection with the field of an adjacent active region. Standard flare loops from Eruption 1 developed over Eruption-2's flux rope and enclosed filament, but these overarching new loops were unable to confine that flux rope/filament. Eruption-1's flare loops, from both TW reconnection and standard-flare-model internal reconnection, were much cooler than Eruption-2's flare loops (GOES thermal temperatures of approx. 9 MK compared to approx. 14 MK). This eruption sequence produced a strong solar energetic particle (SEP) event (10 MeV protons, >10(exp 3) pfu for 43 hrs), apparently starting when Eruption-2's CME blasted through Eruption-1's CME at 5-10 R_s. This occurred because the two CMEs originated in close proximity and in close time sequence: Eruption-1's fast rise started soon after the TW reconnection; the lid removal by Eruption-1's ejection triggered the slow onset of Eruption 2; and Eruption-2's CME, which started approx. 1 hr later, was three times faster than Eruption-1's CME.

Evidence of Significant Energy Input in the Late Phase of A Solar Flare from NuSTAR X-Ray Observations

NASA Technical Reports Server (NTRS)

Kuhar, Matej; Krucker, Sam; Hannah, Iain G.; Glesener, Lindsay; Saint-Hilaire, Pascal; Grefenstette, Brian W.; Hudson, Hugh S.; White, Stephen M.; Smith, David M.; Marsh, Andrew J.;

The Prevalence and Use of Walking Loops in Neighborhood Parks: A National Study.

PubMed

Cohen, Deborah A; Han, Bing; Evenson, Kelly R; Nagel, Catherine; McKenzie, Thomas L; Marsh, Terry; Williamson, Stephanie; Harnik, Peter

2017-02-01

Previous studies indicate that the design of streets and sidewalks can influence physical activity among residents. Park features also influence park use and park-based physical activity. Although individuals can walk on streets and sidewalks, walking loops in parks offer a setting to walk in nature and to avoid interruptions from traffic. Here we describe the use of walking loops in parks and compare the number of park users and their physical activity in urban neighborhood parks with and without walking loops. We analyzed data from the National Study of Neighborhood Parks in which a representative sample of neighborhood parks (n = 174) from 25 U.S. cities with > 100,000 population were observed systematically to document facilities and park users by age group and sex. We compared the number of people and their physical activity in parks with and without walking loops, controlling for multiple factors, including park size, facilities, and population density. Overall, compared with parks without walking loops, on average during an hourly observation, parks with walking loops had 80% more users (95% CI: 42, 139%), and levels of moderate-to-vigorous physical activity were 90% higher (95% CI: 49, 145%). The additional park use and park-based physical activity occurred not only on the walking loops but throughout the park. Walking loops may be a promising means of increasing population level physical activity. Further studies are needed to confirm a causal relationship. Citation: Cohen DA, Han B, Evenson KR, Nagel C, McKenzie TL, Marsh T, Williamson S, Harnik P. 2017. The prevalence and use of walking loops in neighborhood parks: a national study. Environ Health Perspect 125:170-174; http://dx.doi.org/10.1289/EHP293.

The Prevalence and Use of Walking Loops in Neighborhood Parks: A National Study

PubMed Central

Cohen, Deborah A.; Han, Bing; Evenson, Kelly R.; Nagel, Catherine; McKenzie, Thomas L.; Marsh, Terry; Williamson, Stephanie; Harnik, Peter

2016-01-01

Background: Previous studies indicate that the design of streets and sidewalks can influence physical activity among residents. Park features also influence park use and park-based physical activity. Although individuals can walk on streets and sidewalks, walking loops in parks offer a setting to walk in nature and to avoid interruptions from traffic. Objectives: Here we describe the use of walking loops in parks and compare the number of park users and their physical activity in urban neighborhood parks with and without walking loops. Methods: We analyzed data from the National Study of Neighborhood Parks in which a representative sample of neighborhood parks (n = 174) from 25 U.S. cities with > 100,000 population were observed systematically to document facilities and park users by age group and sex. We compared the number of people and their physical activity in parks with and without walking loops, controlling for multiple factors, including park size, facilities, and population density. Results: Overall, compared with parks without walking loops, on average during an hourly observation, parks with walking loops had 80% more users (95% CI: 42, 139%), and levels of moderate-to-vigorous physical activity were 90% higher (95% CI: 49, 145%). The additional park use and park-based physical activity occurred not only on the walking loops but throughout the park. Conclusions: Walking loops may be a promising means of increasing population level physical activity. Further studies are needed to confirm a causal relationship. Citation: Cohen DA, Han B, Evenson KR, Nagel C, McKenzie TL, Marsh T, Williamson S, Harnik P. 2017. The prevalence and use of walking loops in neighborhood parks: a national study. Environ Health Perspect 125:170–174; http://dx.doi.org/10.1289/EHP293 PMID:27517530

Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

PubMed

Hoque, Md Anarul; Zhang, Yong; Chen, Liuqing; Yang, Guangyu; Khatun, Mst Afroza; Chen, Haifeng; Hao, Liu; Feng, Yan

2017-05-19

The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used to investigate StLois's potential for changing enzyme function. By inserting six residues into active site loop 7, the best variant ML7-B6 demonstrated a 16-fold further increase in catalytic efficiency toward ethyl-paraoxon compared with its initial template, that is a 609-fold higher, >10 7 fold substrate specificity shift relative to that of wild-type lactonase. The remodeled variants displayed 760-fold greater organophosphate hydrolysis activity toward the organophosphates parathion, diazinon, and chlorpyrifos. Structure and docking computations support the source of notably inverted enzyme specificity. Considering the fundamental importance of active site loops, the strategy has potential for the rapid generation of novel enzyme functions by loop remodeling.

Hysteresis loop of nonperiodic outbreaks of recurrent epidemics

NASA Astrophysics Data System (ADS)

Liu, Hengcong; Zheng, Muhua; Wu, Dayu; Wang, Zhenhua; Liu, Jinming; Liu, Zonghua

2016-12-01

Most of the studies on epidemics so far have focused on the growing phase, such as how an epidemic spreads and what are the conditions for an epidemic to break out in a variety of cases. However, we discover from real data that on a large scale, the spread of an epidemic is in fact a recurrent event with distinctive growing and recovering phases, i.e., a hysteresis loop. We show here that the hysteresis loop can be reproduced in epidemic models provided that the infectious rate is adiabatically increased or decreased before the system reaches its stationary state. Two ways to the hysteresis loop are revealed, which is helpful in understanding the mechanics of infections in real evolution. Moreover, a theoretical analysis is presented to explain the mechanism of the hysteresis loop.

Discrete Event Command & Control for Networked Teams with Multiple Missions

DTIC Science & Technology

2009-03-16

Architecture for Unmanned Ground Systems ( JAUGS )10, and is an efficient means to realize the high-level OODA loops (observe, orient, decide, act) of 4D...for Unmanned Ground systems ( JAUGS )10, and is an efficient means to realize the OODA loops (observe, orient, decide, act) of 4D/RCS11. DEC is able to

76 FR 48717 - Drawbridge Operation Regulations; Long Island, New York Inland Waterway From East Rockaway Inlet...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... Charity Motorcycle Run. Under this temporary deviation the Loop Parkway Bridge may remain in the closed... operation of the Loop Parkway Bridge, mile 0.7, across Long Creek, and the Captree State Parkway (Robert... bridges listed above to remain in the closed position during this public event. DATES: This deviation is...

Interactions of Twisted Ω-loops in a Model Solar Convection Zone

NASA Astrophysics Data System (ADS)

Jouve, L.; Brun, A. S.; Aulanier, G.

2018-04-01

This study aims at investigating the ability of strong interactions between magnetic field concentrations during their rise through the convection zone to produce complex active regions at the solar surface. To do so, we perform numerical simulations of buoyant magnetic structures evolving and interacting in a model solar convection zone. We first produce a 3D model of rotating convection and then introduce idealized magnetic structures close to the bottom of the computational domain. These structures possess a certain degree of field line twist and they are made buoyant on a particular extension in longitude. The resulting twisted Ω-loops will thus evolve inside a spherical convective shell possessing large-scale mean flows. We present results on the interaction between two such loops with various initial parameters (mainly buoyancy and twist) and on the complexity of the emerging magnetic field. In agreement with analytical predictions, we find that if the loops are introduced with opposite handedness and same axial field direction or the same handedness but opposite axial field, they bounce against each other. The emerging region is then constituted of two separated bipolar structures. On the contrary, if the loops are introduced with the same direction of axial and peripheral magnetic fields and are sufficiently close, they merge while rising. This more interesting case produces complex magnetic structures with a high degree of non-neutralized currents, especially when the convective motions act significantly on the magnetic field. This indicates that those interactions could be good candidates to produce eruptive events like flares or CMEs.

Dynamics of the active site loops in catalyzing aminoacylation reaction in seryl and histidyl tRNA synthetases.

PubMed

Dutta, Saheb; Kundu, Soumya; Saha, Amrita; Nandi, Nilashis

2018-03-01

Aminoacylation reaction is the first step of protein biosynthesis. The catalytic reorganization at the active site of aminoacyl tRNA synthetases (aaRSs) is driven by the loop motions. There remain lacunae of understanding concerning the catalytic loop dynamics in aaRSs. We analyzed the functional loop dynamics in seryl tRNA synthetase from Methanopyrus kandleri ( mk SerRS) and histidyl tRNA synthetases from Thermus thermophilus ( tt HisRS), respectively, using molecular dynamics. Results confirm that the motif 2 loop and other active site loops are flexible spots within the catalytic domain. Catalytic residues of the loops form a network of interaction with the substrates to form a reactive state. The loops undergo transitions between closed state and open state and the relaxation of the constituent residues occurs in femtosecond to nanosecond time scale. Order parameters are higher for constituent catalytic residues which form a specific network of interaction with the substrates to form a reactive state compared to the Gly residues within the loop. The development of interaction is supported from mutation studies where the catalytic domain with mutated loop exhibits unfavorable binding energy with the substrates. During the open-close motion of the loops, the catalytic residues make relaxation by ultrafast librational motion as well as fast diffusive motion and subsequently relax rather slowly via slower diffusive motion. The Gly residues act as a hinge to facilitate the loop closing and opening by their faster relaxation behavior. The role of bound water is analyzed by comparing implicit solvent-based and explicit solvent-based simulations. Loops fail to form catalytically competent geometry in absence of water. The present result, for the first time reveals the nature of the active site loop dynamics in aaRS and their influence on catalysis.

Human Y-Family DNA Polymerase κ Is More Tolerant to Changes in Its Active Site Loop than Its Ortholog Escherichia coli DinB.

PubMed

Antczak, Nicole M; Packer, Morgan R; Lu, Xueguang; Zhang, Ke; Beuning, Penny J

2017-11-20

DNA damage is a constant threat and can be bypassed in a process called translesion synthesis, which is typically carried out by Y-family DNA polymerases. Y-family DNA polymerases are conserved in all domains of life and tend to have specificity for certain types of DNA damage. Escherichia coli DinB and its human ortholog pol κ can bypass specific minor groove deoxyguanine adducts efficiently and are inhibited by major groove adducts, as Y-family DNA polymerases make contacts with the minor groove side of the DNA substrate and lack contacts with the major groove at the nascent base pair. DinB is inhibited by major groove adducts more than pol κ, and they each have active site loops of different lengths, with four additional amino acids in the DinB loop. We previously showed that the R35A active site loop mutation in DinB allows for bypass of the major groove adduct N 6 -furfuryl-dA. These observations led us to investigate the different active site loops by creating loop swap chimeras of DinB with a pol κ loop and vice versa by changing the loop residues in a stepwise fashion. We then determined their activity with undamaged DNA or DNA containing N 2 -furfuryl-dG or N 6 -furfuryl-dA. The DinB proteins with the pol kappa loop have low activity on all templates but have decreased misincorporation compared to either wild-type protein. The kappa proteins with the DinB loop retain activity on all templates and have decreased misincorporation compared to either wild-type protein. We assessed the thermal stability of the proteins and observed an increase in stability in the presence of all DNA templates and additional increases generally only in the presence of the undamaged and N 2 -furfuryl-dG adduct and dCTP, which correlates with activity. Overall we find that pol κ is more tolerant to changes in the active site loop than DinB.

The Use of the Ex Vivo Chandler Loop Apparatus to Assess the Biocompatibility of Modified Polymeric Blood Conduits

PubMed Central

Slee, Joshua B.; Alferiev, Ivan S.; Levy, Robert J.; Stachelek, Stanley J.

2014-01-01

The foreign body reaction occurs when a synthetic surface is introduced to the body. It is characterized by adsorption of blood proteins and the subsequent attachment and activation of platelets, monocyte/macrophage adhesion, and inflammatory cell signaling events, leading to post-procedural complications. The Chandler Loop Apparatus is an experimental system that allows researchers to study the molecular and cellular interactions that occur when large volumes of blood are perfused over polymeric conduits. To that end, this apparatus has been used as an ex vivo model allowing the assessment of the anti-inflammatory properties of various polymer surface modifications. Our laboratory has shown that blood conduits, covalently modified via photoactivation chemistry with recombinant CD47, can confer biocompatibility to polymeric surfaces. Appending CD47 to polymeric surfaces could be an effective means to promote the efficacy of polymeric blood conduits. Herein is the methodology detailing the photoactivation chemistry used to append recombinant CD47 to clinically relevant polymeric blood conduits and the use of the Chandler Loop as an ex vivo experimental model to examine blood interactions with the CD47 modified and control conduits. PMID:25178087

Comparative assessment of the efficacy of closed helical loop and T-loop for space closure in lingual orthodontics-a finite element study.

PubMed

Chacko, Ajay; Tikku, Tripti; Khanna, Rohit; Maurya, Rana Pratap; Srivastava, Kamna

2018-05-28

Retraction in lingual orthodontics has biomechanical differences when compared to labial orthodontics, which is not yet established. Thus, we have intended to compare the biomechanical characteristics of closed helical loop and T-loop on 1 mm activation with 30° of compensatory curvatures during retraction in lingual orthodontics. STb lingual brackets were indirectly bonded to maxillary typhodont model that was scanned to obtain FEM model. Closed helical loop (2 × 7 mm) and T-loop (6 × 2 × 7 mm) of 0.016″ × 0.016″ TMA wire were modeled without preactivation bends. Preactivation bends at 30° were given in the software. Boundary conditions were set. The force (F) and moment (M) of both the loops were determined on 1 mm activation, using ANSYS software. M/F ratio was also calculated for both the loops. T-loop exerted less force, thus increased M/F ratio as compared to closed helical loop on 1 mm activation. When torque has to be preserved in the anterior segment during retraction in lingual orthodontics, T-loop can be preferred over closed helical loop.

The Significance of Ras Activity in Pancreatic Cancer Initiation

PubMed Central

Logsdon, Craig D.; Lu, Weiqin

2016-01-01

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility.

PubMed

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I; Hantschel, Oliver

2014-11-17

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

NASA Astrophysics Data System (ADS)

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

2014-11-01

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

L-Band Ionosphere Scintillations Observed by A GNSS Receiver Array at HAARP

NASA Astrophysics Data System (ADS)

Morton, Y.; Pelgrum, W.; van Graas, F.

2011-12-01

As we enter a new solar maximum period, GNSS receivers, especially the ones operating in high latitude and equatorial regions, are facing an increasing threat from ionosphere scintillations. The increased solar activities, however, also offer a great opportunity to collect scintillation data to gain better understandings of scintillation effects on GNSS signals. During the past decade, many GPS receivers have been deployed around the globe to monitor ionosphere scintillations. Most of these GPS receivers are commercial receivers whose tracking mechanisms are not designed to operate under ionosphere scintillation. When strong scintillations occur, these receivers will either generate erroneous outputs or completely lose lock. Even when the scintillation is mild, the tracking loop outputs are not true representation of the signal parameters due the tracking loop transfer function. High quality, unprocessed GNSS receiver front end raw IF samples collected during ionosphere scintillations are necessary to produce realistic scintillation signal parameter estimations. In this presentation, we will update our effort in establishing a unique GNSS receiver array at HAARP, Alaska to collect GPS and GLONASS satellite signals at various stages of the GNSS receiver processing. Signal strength, carrier phase, and relative TEC measurements generated by the receiver array as well as additional on-site diagnostic instrumentation measurements obtained from two active heating experiment campaigns conducted in 2011 will be presented. Additionally, we will also highlight and contrast the artificial heating experiment results with observations of natural scintillation events captured by our receivers using an automatic event trigger mechanism during the past year. These interesting results demonstrate the feasibility and effectiveness of our experimental data collection system in providing insightful details of ionosphere responses to active perturbations and natural disturbances.

Visualizing Active-Site Dynamics in Single Crystals of HePTP: Opening of the WPD Loop Involves Coordinated Movement of the E Loop

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

D Critton; L Tautz; R Page

2011-12-31

Phosphotyrosine hydrolysis by protein tyrosine phosphatases (PTPs) involves substrate binding by the PTP loop and closure over the active site by the WPD loop. The E loop, located immediately adjacent to the PTP and WPD loops, is conserved among human PTPs in both sequence and structure, yet the role of this loop in substrate binding and catalysis is comparatively unexplored. Hematopoietic PTP (HePTP) is a member of the kinase interaction motif (KIM) PTP family. Compared to other PTPs, KIM-PTPs have E loops that are unique in both sequence and structure. In order to understand the role of the E loopmore » in the transition between the closed state and the open state of HePTP, we identified a novel crystal form of HePTP that allowed the closed-state-to-open-state transition to be observed within a single crystal form. These structures, which include the first structure of the HePTP open state, show that the WPD loop adopts an 'atypically open' conformation and, importantly, that ligands can be exchanged at the active site, which is critical for HePTP inhibitor development. These structures also show that tetrahedral oxyanions bind at a novel secondary site and function to coordinate the PTP, WPD, and E loops. Finally, using both structural and kinetic data, we reveal a novel role for E-loop residue Lys182 in enhancing HePTP catalytic activity through its interaction with Asp236 of the WPD loop, providing the first evidence for the coordinated dynamics of the WPD and E loops in the catalytic cycle, which, as we show, is relevant to multiple PTP families.« less

Observations of Reconnection Flows in a Flare on the Solar Disk

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

Wang, Juntao; Simões, P. J. A.; Jeffrey, N. L. S.

Magnetic reconnection is a well-accepted part of the theory of solar eruptive events, though the evidence is still circumstantial. Intrinsic to the reconnection picture of a solar eruptive event, particularly in the standard model for two-ribbon flares (CSHKP model), are an advective flow of magnetized plasma into the reconnection region, expansion of field above the reconnection region as a flux rope erupts, retraction of heated post-reconnection loops, and downflows of cooling plasma along those loops. We report on a unique set of Solar Dynamics Observatory /Atmospheric Imaging Assembly imaging and Hinode /EUV Imaging Spectrometer spectroscopic observations of the disk flaremore » SOL2016-03-23T03:54 in which all four flows are present simultaneously. This includes spectroscopic evidence for a plasma upflow in association with large-scale expanding closed inflow field. The reconnection inflows are symmetric, and consistent with fast reconnection, and the post-reconnection loops show a clear cooling and deceleration as they retract. Observations of coronal reconnection flows are still rare, and most events are observed at the solar limb, obscured by complex foregrounds, making their relationship to the flare ribbons, cusp field, and arcades formed in the lower atmosphere difficult to interpret. The disk location and favorable perspective of this event have removed these ambiguities giving a clear picture of the reconnection dynamics.« less

Simulating nanostorm heating in coronal loops using hydrodynamics and non-thermal particle evolution

NASA Astrophysics Data System (ADS)

Migliore, Christina; Winter, Henry; Murphy, Nicholas

2018-01-01

The solar corona is filled with loop-like structures that appear bright against the background when observed in the extreme ultraviolet (EUV). These loops have several remarkable properties that are not yet well understood. Warm loops (∼ 1 MK) appear to be ∼ 2 ‑ 9 times as dense at their apex as the predictions of hydrostatic atmosphere models. These loops also appear to be of constant cross-section despite the fact that the field strength in a potential magnetic field should decrease in the corona, causing the loops to expand. It is not clear why many active region loops appear to be of constant cross-section. Theories range from an internal twist of the magnetic field to observational effects. In this work we simulate active region loops heated by nanoflare storms using a dipolar magnetic field. We calculate the hydrodynamic properties for each loop using advanced hydrodynamics codes to simulate the corona and chromospheric response and basic dipole models to represent the magnetic fields of the loops. We show that even modest variations of the magnetic field strength along the loop can lead to drastic changes in the density profiles of active region loops, and they can also explain the overpressure at the apex of these loops. Synthetic AIA images of each loop are made to show the observable consequences of varying magnetic field strengths along the loop’s axis of symmetry. We also show how this work can lead to improved modeling of larger solar and stellar flares.

Searching for Spectroscopic Signs of Termination Shocks in Solar Flares

NASA Astrophysics Data System (ADS)

Galan, G.; Polito, V.; Reeves, K.

2017-12-01

The standard flare model predicts the presence of a termination shock located above the flare loop tops, however terminations shocks have not yet been well observed. We analyze flare observations by the Interface Region Imaging Spectrograph (IRIS), which provides cotemporal UV imaging and spectral data. Specifically, we study plasma emissions in the Fe XXI line, formed at the very hot plasma temperatures in flares (> 10 MK). Imaging observations that point to shocks include fast hot reconnection downflows above the loop tops and localized dense, bright plasma at the loop tops; spectral signatures that suggest shocks in the locality of the loop tops include redshifts and nonthermal broadening of the Fe XXI line. We identify possibly significant redshifts in some on-disk flare events observed by IRIS. Redshifts are observed in the vicinity of the bright loop top source that is thought to coincide with the site of the shock. In these events, the Fe XXI emissions at the time of the redshifted structures are dominated by at the at-rest components. The much more less intense redshifted components are broader, with velocities of 200 km/s. The spatial location of these shifts might indicate plasma motions and speeds indicative of termination shocks. This work is supported by the NSF-REU solar physics program at SAO, grant number AGS-1560313, and by NASA Grant NNX15AJ93G. Keywords: Solar flares, Solar magnetic reconnection, Termination shocks

Loop engineering reveals the importance of active-site-decorating loops and gating residue in substrate affinity modulation of arginine deiminase (an anti-tumor enzyme).

PubMed

Cheng, Feng; Yang, Jianhua; Bocola, Marco; Schwaneberg, Ulrich; Zhu, Leilei

2018-05-05

Protein engineering of enzyme loop regions is an effective strategy to improve enzymatic properties. Previous studies that aimed to boost the activity of PpADI (an arginine deiminase from Pseudomonas plecoglossicida) under physiological conditions yielded several significantly improved variants that harbor substitutions predominantly located in active-site-decorating loops. A multi-site saturation mutagenesis at four positions in loop 1 (37, 38, 42, and 43) and three positions in loop 4 (402, 403, and 404) was performed to elucidate the importance of these loops in modulating the substrate affinity of PpADI. The identified "best" variant (M6-L1-4) showed a decreased S 0.5 ('K M ') of 0.48 mM compared with the parent M6 (0.81 mM). Subsequently, a rational design to recombine beneficial substitutions within loops 1 and 4 yielded variant L6 with a substantially decreased S 0.5 value (0.17 mM). A comprehensive simulation analysis resulted in a conclusion that high loop flexibility (especially the gating residue Arg400) is beneficial for substrate affinity due to less efficient blocking of the active site. Copyright © 2018 Elsevier Inc. All rights reserved.

Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent

PubMed Central

Bonenfant, Débora; Rubert, Joëlle; Vangrevelinghe, Eric; Scheufler, Clemens; Marque, Fanny; Régnier, Catherine H.; De Pover, Alain; Ryckelynck, Hugues; Bhagwat, Neha; Koppikar, Priya; Goel, Aviva; Wyder, Lorenza; Tavares, Gisele; Baffert, Fabienne; Pissot-Soldermann, Carole; Manley, Paul W.; Gaul, Christoph; Voshol, Hans; Levine, Ross L.; Sellers, William R.; Hofmann, Francesco; Radimerski, Thomas

2016-01-01

JAK inhibitors are being developed for the treatment of rheumatoid arthritis, psoriasis, myeloproliferative neoplasms and leukemias. Most of these drugs target the ATP-binding pocket and stabilize the active conformation of the JAK kinases. This type-I binding mode leads to an increase in JAK activation-loop phosphorylation, despite blockade of kinase function. Here we report that stabilizing the inactive state via type-II inhibition acts in the opposite manner, leading to a loss of activation-loop phosphorylation. We used X-ray crystallography to corroborate the binding mode and report for the first time the crystal structure of the JAK2 kinase domain in an inactive conformation. Importantly, JAK inhibitor-induced activation-loop phosphorylation requires receptor interaction, as well as intact kinase and pseudokinase domains. Hence, depending on the respective conformation stabilized by a JAK inhibitor, hyperphosphorylation of the activation-loop may or may not be elicited. PMID:22684457

Transequatorial loops interconnecting McMath regions 12472 and 12474

NASA Technical Reports Server (NTRS)

Svestka, Z.; Krieger, A. S.; Chase, R. C.; Howard, R.

1977-01-01

The paper reviews the life history of one transequatorial loop in a system observed in soft X-rays for at least 1.5 days and which interconnected a newly born active region with an old region. The birth of the selected loop is discussed along with properties of the interconnected active regions, sharpening and brightening of the loop, decay of the loop system, and physical relations between the interconnected regions. It is concluded that: (1) the loop was most probably born via reconnection of magnetic-field lines extending from the two active regions toward the equator, which occurred later than 33 hr after the younger region was born; (2) the fully developed interconnection was composed of several loops, all of which appeared to be rooted in a spotless magnetic hill of preceding northern polarity but were spread over two separate spotty regions of southern polarity in the magnetically complex new region; (3) the loop electron temperature increased from 2.1 million to 3.1 million K in one to three hours when the loop system brightened; and (4) the loops became twisted during the brightening, possibly due to their rise in the corona while remaining rooted in moving magnetic features in the younger region.

78 FR 53664 - Drawbridge Operation Regulations; Long Island, New York Inland Waterway From East Rockaway Inlet...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... deviation the Loop Parkway and the Meadowbrook Parkway Bridges may remain in the closed position between 11... operation of the Loop Parkway Bridge, mile 0.7, across Long Creek, and the Meadowbrook Parkway Bridge, mile... remain in the closed position during this public event. DATES: This deviation is effective from 11 a.m...

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

PubMed

Suebsuwong, Chalada; Pinkas, Daniel M; Ray, Soumya S; Bufton, Joshua C; Dai, Bing; Bullock, Alex N; Degterev, Alexei; Cuny, Gregory D

2018-02-15

Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Investigating and predicting landslides using a rainfall runoff model in Norway

NASA Astrophysics Data System (ADS)

Kråbøl, Eline; Skaugen, Thomas; Devoli, Graziella; Xu, Chong-Yu

2016-04-01

Landslides are amongst the most destructive natural hazards, causing damage to infrastructures, such as roads, railroads and houses, and can, in a worst-case scenario, take lives. A better understanding of the triggering processes of landslides are important as it enables us to perform better forecasts, improve mapping of zones with landslide risk and carry out mitigation measures. In this study, a parameter-parsimonious rainfall-runoff model, DDD (Distance Distribution Dynamics), is used to simulate the hydrological conditions for rainfall-induced landslide events. The model estimates the capacity of the subsurface reservoir at different levels of saturation and predicts overland flow. The subsurface in the DDD has a 2-D representation in that it calculates the saturated and unsaturated soil moisture along a hillslope representing the entire catchment in question. In this study, 50 landslide events in 10 catchments in Southern Norway are investigated. Characteristics of the subsurface states, before, during and after the landslide are analysed for the whole catchment and at three points (lower, middle and upper part) of the hillslope. Preliminary results show that the hysteretic loop of storage and discharge follow complex clockwise and anti-clockwise patterns. Anti-clockwise loops occur more frequent, except for the middle part of the hillslope. In the upper part of the hillslope, anti-clockwise loop occur almost exclusively (94 %). Evaluated for the entire catchment, 57 % of the landslide events occurred at maximum saturation, while 77 % of the events occurred at saturation above 80 %. We found the majority of the landslide events to be associated with the rising limb and the top of the hysteretic curve with 64 % and 17 %, respectively. Overland flow was found for 68 % of the events.

TRACE Images of the Solar Chromosphere, Transition Region, and Low Corona at High Cadence and High Spatial Resolution

NASA Astrophysics Data System (ADS)

Tarbell, T. D.; Handy, B. N.; Judge, P. G.

1999-05-01

We present TRACE images and movies showing C IV emission (transition region at 80,000 degrees) and UV continuum (temperature minimum region) of quiet and active regions. TRACE images using the 1550, 1600, and 1700 Angstroms filters can be combined to estimate the total emission in the C IV 1548 and 1550 lines and the UV continuum. These are supplemented in different observations with MDI magnetograms, TRACE 171 Angstroms images (Fe IX/X and perhaps O VI), and SUMER spectra of chromospheric and transition region lines from SOHO JOP 72. In quiet sun, bright C IV transients are seen in the vicinity of flux emergence, flux cancellation, and less dramatic interactions of small magnetic structures. Some of these are accompanied by high-velocity explosive events seen in SUMER spectra. The C IV emission can be well-separated from the photospheric magnetic footpoints, suggesting that it takes place on current sheets higher in the atmosphere separating different flux systems. In active regions, both bright and dark fibrils or loops are seen in C IV. Many nano/micro/sub flares are seen, some but not all of which are associated with emerging flux. The C IV emission of "moss" regions, footpoints of hot coronal loops, is contrasted with that of similar plage which does not have hot loops above it. This work was supported by the NASA contracts and grants for TRACE, MDI, and SOHO.

Phosphorylation of threonine 290 in the activation loop of Tpl2/Cot is necessary but not sufficient for kinase activity.

PubMed

Luciano, Brenda S; Hsu, Sang; Channavajhala, Padma L; Lin, Lih-Ling; Cuozzo, John W

2004-12-10

Cot/Tpl2/MAP3K8 is a serine/threonine kinase known to activate the ERK, p38, and JNK kinase pathways. Studies of Tpl2 knock-out mice reveal a clear defect in tumor necrosis factor-alpha production, although very little detail is known about its regulation and the signaling events involved. In the present study we demonstrated that phosphorylation of Cot was required for its maximal activity as phosphatase treatment of Cot decreased its kinase activity. The Cot sequence contains a conserved threonine at position 290 in the activation loop of the kinase domain. We found that mutation of this residue to alanine eliminated its ability to activate MEK/ERK and NF-kappaB pathways, whereas a phosphomimetic mutation to aspartic acid could rescue the ability to activate MEK. Thr-290 was also required for robust autophosphorylation of Cot. Antibody generated to phospho-Thr-290-Cot recognized both wild-type and kinase-dead Cot, suggesting that phosphorylation of Thr-290 did not occur through autophosphorylation but via another kinase. We showed that Cot was constitutively phosphorylated at Thr-290 in transfected human embryonic kidney 293T cells as well as human monocytes as this residue was phosphorylated in unstimulated and lipopolysaccharide-stimulated cells to the same degree. Treatment with herbimycin A inhibited Cot activity in the MEK/ERK pathway but did not inhibit phosphorylation at Thr-290. Together these results showed that phosphorylation of Cot at Thr-290 is necessary but not sufficient for full kinase activity in the MEK/ERK pathway.

Fundamental Characteristics of AAA+ Protein Family Structure and Function.

PubMed

Miller, Justin M; Enemark, Eric J

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

Can Flare Loops Contribute to the White-light Emission of Stellar Superflares?

NASA Astrophysics Data System (ADS)

Heinzel, P.; Shibata, K.

2018-06-01

Since the discovery of stellar superflares by the Kepler satellite, these extremely energetic events have been studied in analogy to solar flares. Their white-light (WL) continuum emission has been interpreted as being produced by heated ribbons. In this paper, we compute the WL emission from overlying flare loops depending on their density and temperature and show that, under conditions expected during superflares, the continuum brightening due to extended loop arcades can significantly contribute to stellar flux detected by Kepler. This requires electron densities in the loops of 1012‑1013 cm‑3 or higher. We show that such densities, exceeding those typically present in solar-flare loops, can be reached on M-dwarf and solar-type superflare stars with large starspots and much stronger magnetic fields. Quite importantly, the WL radiation of loops is not very sensitive to their temperature and thus both cool as well as hot loops may contribute. We show that the WL intensity emergent from optically thin loops is lower than the blackbody radiation from flare ribbons, but the contribution of loops to total stellar flux can be quite important due to their significant emitting areas. This new scenario for interpreting superflare emission suggests that the observed WL flux is due to a mixture of the ribbon and loop radiation and can be even loop-dominated during the gradual phase of superflares.

Neural principles of memory and a neural theory of analogical insight

NASA Astrophysics Data System (ADS)

Lawson, David I.; Lawson, Anton E.

1993-12-01

Grossberg's principles of neural modeling are reviewed and extended to provide a neural level theory to explain how analogies greatly increase the rate of learning and can, in fact, make learning and retention possible. In terms of memory, the key point is that the mind is able to recognize and recall when it is able to match sensory input from new objects, events, or situations with past memory records of similar objects, events, or situations. When a match occurs, an adaptive resonance is set up in which the synaptic strengths of neurons are increased; thus a long term record of the new input is formed in memory. Systems of neurons called outstars and instars are presumably the underlying units that enable this to occur. Analogies can greatly facilitate learning and retention because they activate the outstars (i.e., the cells that are sampling the to-be-learned pattern) and cause the neural activity to grow exponentially by forming feedback loops. This increased activity insures the boost in synaptic strengths of neurons, thus causing storage and retention in long-term memory (i.e., learning).

System Control for the Transitional DCS.

DTIC Science & Technology

1978-12-01

hour. The equipment destroyed includes the TTC-39 switch, all RF and multiplex equipment, emergency power equipment, distribution frames, antennal and...switch executes loop test to Rhein Main ULS, activating a local alarm at Donnersberg. Since restoral activity has not already been completed, alarm is...ITEM COMMENTS (BYTES) Loop ID Switch number and physical loop number 6 (BCD). Loop circuit CCSD 8 Telephone number 3 Location Physical location of

A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

PubMed

Thrower, Edwin C; Yuan, Jingzhen; Usmani, Ashar; Liu, Yannan; Jones, Courtney; Minervini, Samantha N; Alexandre, Martine; Pandol, Stephen J; Guha, Sushovan

2011-01-01

Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.

Modal gating of muscle nicotinic acetylcholine receptors

NASA Astrophysics Data System (ADS)

Vij, Ridhima

Many ion channels exhibit multiple patterns of kinetic activity in single-channel currents. This behavior is rare in WT mouse muscle nicotinic acetylcholine receptors (AChRs), where A2C↔A2O gating events are well-described by single exponentials. Also, single-channel open probability (PO) is essentially homogeneous at a given agonist concentration in the WT receptors. Here I report that perturbations of almost all the residues in loop C (alpha188-alpha199, at the agonist binding site) generate heterogeneity in PO ('modes'). Such unsettled activity was apparent with an alanine substitution at all positions in loop C (except alphaY190 and alphaY198) and with different side chain substitutions at alphaP197 for both adult- and fetal-type AChRs. I used single channel electrophysiology along with site-directed mutagenesis to study modal gating in AChRs consequent to mutations/deletions in loop C. The multiple patterns of kinetic activity arose from the difference in agonist affinity rather than in intrinsic AChR gating. Out of the four different agonists used to study the modal behavior, acetylcholine (ACh) showed a higher degree of kinetic heterogeneity compared to others. The time constant for switching between modes was long (~mins), suggesting that they arise from alternative, stable protein conformations. By studying AChRs having only 1 functional binding site, I attempted to find the source of the affinity difference, which was traced mainly to the alphadelta agonist site. Affinity at the neurotransmitter binding site is mainly determined by a core of five aromatic residues (alphaY93, alphaW149, alphaY190, alphaY198 and deltaW57). Phenylalanine substitutions at all aromatic residues except alphaY93 resulted in elimination of modes. Modes were also eliminated by alanine mutation at deltaW57 on the complementary side but not at other aromatics. Also, by substituting four gamma subunit residues into the delta subunit on the complementary beta sheet, I found that modes were reduced. Based on our results, we propose that WT loop C has an important role in determining resting affinity, in part by making stable interactions with the complementary surface of the alphadelta binding pocket. We suggest a possible structural basis for the fluctuations caused by loop C perturbations and propose that at the alphadelta agonist binding site, both loop C and the complementary subunit surface can adopt alternative conformations and interact with each other with respect to the aromatic core, to cause the variations in affinity.

An Allosteric Cross-Talk Between the Activation Loop and the ATP Binding Site Regulates the Activation of Src Kinase

NASA Astrophysics Data System (ADS)

Pucheta-Martínez, Encarna; Saladino, Giorgio; Morando, Maria Agnese; Martinez-Torrecuadrada, Jorge; Lelli, Moreno; Sutto, Ludovico; D'Amelio, Nicola; Gervasio, Francesco Luigi

2016-04-01

Phosphorylation of the activation loop is a fundamental step in the activation of most protein kinases. In the case of the Src tyrosine kinase, a prototypical kinase due to its role in cancer and its historic importance, phosphorylation of tyrosine 416 in the activation loop is known to rigidify the structure and contribute to the switch from the inactive to a fully active form. However, whether or not phosphorylation is able per-se to induce a fully active conformation, that efficiently binds ATP and phosphorylates the substrate, is less clear. Here we employ a combination of solution NMR and enhanced-sampling molecular dynamics simulations to fully map the effects of phosphorylation and ATP/ADP cofactor loading on the conformational landscape of Src tyrosine kinase. We find that both phosphorylation and cofactor binding are needed to induce a fully active conformation. What is more, we find a complex interplay between the A-loop and the hinge motion where the phosphorylation of the activation-loop has a significant allosteric effect on the dynamics of the C-lobe.

Properties of a large-scale interplanetary loop structure as deduced from low-energy proton anisotropy and magnetic field measurements

NASA Technical Reports Server (NTRS)

Tranquille, C.; Sanderson, T. R.; Marsden, R. G.; Wenzel, K.-P.; Smith, E. J.

1987-01-01

Correlated particle and magnetic field measurements by the ISEE 3 spacecraft are presented for the loop structure behind the interplanetary traveling shock event of Nov. 12, 1978. Following the passage of the turbulent shock region, strong bidirectional streaming of low-energy protons is observed for approximately 6 hours, corresponding to a loop thickness of about 0.07 AU. This region is also characterized by a low relative variance of the magnetic field, a depressed proton intensity, and a reduction in the magnetic power spectral density. Using quasi-linear theory applied to a slab model, a value of 3 AU is derived for the mean free path during the passage of the closed loop. It is inferred from this observation that the proton regime associated with the loop structure is experiencing scatter-free transport and that either the length of the loop is approximately 3 AU between the sun and the earth or else the protons are being reflected at both ends of a smaller loop.

Mini-filament Eruption as the Initiation of a Jet along Coronal Loops

NASA Astrophysics Data System (ADS)

Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Yang, Bo; Xu, Zhe; Xiang, Yongyuan

2016-10-01

Minifilament eruptions (MFEs) and coronal jets are different types of solar small-scale explosive events. We report an MFE observed at the New Vacuum Solar Telescope (NVST). As seen in the NVST Hα images, during the rising phase, the minifilament erupts outward orthogonally to its length, accompanied with a flare-like brightening at the bottom. Afterward, dark materials are found to possibly extend along the axis of the expanded filament body. The MFE is analogous to large filament eruptions. However, a simultaneous observation of the Solar Dynamics Observatory shows that a jet is initiated and flows out along nearby coronal loops during the rising phase of the MFE. Meanwhile, small hot loops, which connect the original eruptive site of the minifilament to the footpoints of the coronal loops, are formed successively. A differential emission measure analysis demonstrates that, on the top of the new small loops, a hot cusp structure exists. We conjecture that the magnetic fields of the MFE interact with magnetic fields of the coronal loops. This interaction is interpreted as magnetic reconnection that produces the jet and the small hot loops.

The uncoupling of catalysis and translocation in the viral RNA-dependent RNA polymerase

PubMed Central

Shu, Bo; Gong, Peng

2017-01-01

ABSTRACT The nucleotide addition cycle of nucleic acid polymerases includes 2 major events: the pre-chemistry active site closure leading to the addition of one nucleotide to the product chain; the post-chemistry translocation step moving the polymerase active site one position downstream on its template. In viral RNA-dependent RNA polymerases (RdRPs), structural and biochemical evidences suggest that these 2 events are not tightly coupled, unlike the situation observed in A-family polymerases such as the bacteriophage T7 RNA polymerase. Recently, an RdRP translocation intermediate crystal structure of enterovirus 71 shed light on how translocation may be controlled by elements within RdRP catalytic motifs, and a series of poliovirus apo RdRP crystal structures explicitly suggest that a motif B loop may assist the movement of the template strand in late stages of transcription. Implications of RdRP catalysis-translocation uncoupling and the remaining challenges to further elucidate RdRP translocation mechanism are also discussed. PMID:28277928

Genome-Wide Identification of Mitogen-Activated Protein Kinase Gene Family across Fungal Lineage Shows Presence of Novel and Diverse Activation Loop Motifs

PubMed Central

Mohanta, Tapan Kumar; Mohanta, Nibedita; Parida, Pratap; Panda, Sujogya Kumar; Ponpandian, Lakshmi Narayanan; Bae, Hanhong

2016-01-01

The mitogen-activated protein kinase (MAPK) is characterized by the presence of the T-E-Y, T-D-Y, and T-G-Y motifs in its activation loop region and plays a significant role in regulating diverse cellular responses in eukaryotic organisms. Availability of large-scale genome data in the fungal kingdom encouraged us to identify and analyse the fungal MAPK gene family consisting of 173 fungal species. The analysis of the MAPK gene family resulted in the discovery of several novel activation loop motifs (T-T-Y, T-I-Y, T-N-Y, T-H-Y, T-S-Y, K-G-Y, T-Q-Y, S-E-Y and S-D-Y) in fungal MAPKs. The phylogenetic analysis suggests that fungal MAPKs are non-polymorphic, had evolved from their common ancestors around 1500 million years ago, and are distantly related to plant MAPKs. We are the first to report the presence of nine novel activation loop motifs in fungal MAPKs. The specificity of the activation loop motif plays a significant role in controlling different growth and stress related pathways in fungi. Hence, the presences of these nine novel activation loop motifs in fungi are of special interest. PMID:26918378

Sparkling extreme-ultraviolet bright dots observed with Hi-C

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

Régnier, S.; Alexander, C. E.; Walsh, R. W.

Observing the Sun at high time and spatial scales is a step toward understanding the finest and fundamental scales of heating events in the solar corona. The high-resolution coronal (Hi-C) instrument has provided the highest spatial and temporal resolution images of the solar corona in the EUV wavelength range to date. Hi-C observed an active region on 2012 July 11 that exhibits several interesting features in the EUV line at 193 Å. One of them is the existence of short, small brightenings 'sparkling' at the edge of the active region; we call these EUV bright dots (EBDs). Individual EBDs havemore » a characteristic duration of 25 s with a characteristic length of 680 km. These brightenings are not fully resolved by the SDO/AIA instrument at the same wavelength; however, they can be identified with respect to the Hi-C location of the EBDs. In addition, EBDs are seen in other chromospheric/coronal channels of SDO/AIA, which suggests a temperature between 0.5 and 1.5 MK. Based on their frequency in the Hi-C time series, we define four different categories of EBDs: single peak, double peak, long duration, and bursty. Based on a potential field extrapolation from an SDO/HMI magnetogram, the EBDs appear at the footpoints of large-scale, trans-equatorial coronal loops. The Hi-C observations provide the first evidence of small-scale EUV heating events at the base of these coronal loops, which have a free magnetic energy of the order of 10{sup 26} erg.« less

Functional and structural characterization of the pentapeptide insertion of Theileria annulata lactate dehydrogenase by site-directed mutagenesis, comparative modeling and molecular dynamics simulations.

PubMed

Erdemir, Aysegul; Mutlu, Ozal

2017-06-01

Lactate dehydrogenase (LDH) is an important metabolic enzyme in glycolysis and it has been considered as the main energy source in many organisms including apicomplexan parasites. Differences at the active site loop of the host and parasite LDH's makes this enzyme an attractive target for drug inhibitors. In this study, five amino acid insertions in the active site pocket of Theileria annulata LDH (TaLDH) were deleted by PCR-based site-directed mutagenesis, expression and activity analysis of mutant and wild type TaLDH enzymes were performed. Removal of the insertion at the active site loop caused production of an inactive enzyme. Furthermore, structures of wild and mutant enzymes were predicted by comparative modeling and the importance of the insertions at the active site loop were also assigned by molecular docking and dynamics simulations in order to evaluate essential role of this loop for the enzymatic activity. Pentapeptide insertion removal resulted in loss of LDH activity due to deletion of Trp96 and conformational change of Arg98 because of loop instability. Analysis of wild type and mutant enzymes with comparative molecular dynamics simulations showed that the fluctuations of the loop residues increase in mutant enzyme. Together with in silico studies, in vitro results revealed that active site loop has a vital role in the enzyme activity and our findings promise hope for the further drug design studies against theileriosis and other apicomplexan parasite diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-Potential Magnetic Fields and Magnetic Reconnection In Low Collisional Plasmas-Discovery of Solar EUV Mini-Sigmoids and Development of Novel In-Space Propulsion Systems

NASA Astrophysics Data System (ADS)

Chesny, David

Magnetic reconnection is the source of many of the most powerful explosions of astrophysical plasmas in the universe. Blazars, magnetars, stellar atmospheres, and planetary magnetic fields have all been shown to be primary sites of strong reconnection events. For studying the fundamental physics behind this process, the solar atmosphere is our most accessible laboratory setting. Magnetic reconnection resulting from non-potential fields leads to plasma heating and particle acceleration, often in the form of explosive activity, contributing to coronal heating and the solar wind. Large-scale non-potential (sigmoid) fields in the solar atmosphere are poorly understood due to their crowded neighborhoods. For the first time, small-scale, non-potential loop structures have been observed in quiet Sun EUV observations. Fourteen unique mini-sigmoid events and three diffuse non-potential loops have been discovered, suggesting a multi-scaled self-similarity in the sigmoid formation process. These events are on the order of 10 arcseconds in length and do not appear in X-ray emissions, where large-scale sigmoids are well documented. We have discovered the first evidence of sigmoidal structuring in EUV bright point phenomena, which are prolific events in the solar atmosphere. Observations of these mini-sigmoids suggest that they are being formed via tether-cutting reconnection, a process observed to occur at active region scales. Thus, tether-cutting is suggested to be ubiquitous throughout the solar atmosphere. These dynamics are shown to be a function of the free magnetic energy in the quiet Sun network. Recently, the reconnection process has been reproduced in Earth-based laboratory tokamaks. Easily achievable magnetic field configurations can induce reconnection and result in ion acceleration. Here, magnetic reconnection is utilized as the plasma acceleration mechanism for a theoretical propulsion system. The theory of torsional spine reconnection is shown to result in ion velocities of > 3000 km s-1 and thrusts on the order of 3-15 N. As current in-use ion propulsion technology can only achieve ˜ 30 km s-1, the proposed design can substantially increase thrust on a spacecraft and provide for fast manned interplanetary travel.

GROWING TRANSVERSE OSCILLATIONS OF A MULTISTRANDED LOOP OBSERVED BY SDO/AIA

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

Wang, Tongjiang; Ofman, Leon; Su, Yang

The first evidence of transverse oscillations of a multistranded loop with growing amplitudes and internal coupling observed by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory is presented. The loop oscillation event occurred on 2011 March 8, triggered by a coronal mass ejection (CME). The multiwavelength analysis reveals the presence of multithermal strands in the oscillating loop, whose dynamic behaviors are temperature-dependent, showing differences in their oscillation amplitudes, phases, and emission evolution. The physical parameters of growing oscillations of two strands in 171 A are measured and the three-dimensional loop geometry is determined using STEREO-A/EUVI data. These strandsmore » have very similar frequencies, and between two 193 A strands a quarter-period phase delay sets up. These features suggest the coupling between kink oscillations of neighboring strands and the interpretation by the collective kink mode as predicted by some models. However, the temperature dependence of the multistranded loop oscillations was not studied previously and needs further investigation. The transverse loop oscillations are associated with intensity and loop width variations. We suggest that the amplitude-growing kink oscillations may be a result of continuous non-periodic driving by magnetic deformation of the CME, which deposits energy into the loop system at a rate faster than its loss.« less

Novel Use of Glucagon in a Closed-Loop System for Prevention of Hypoglycemia in Type 1 Diabetes

PubMed Central

Castle, Jessica R.; Engle, Julia M.; Youssef, Joseph El; Massoud, Ryan G.; Yuen, Kevin C.J.; Kagan, Ryland; Ward, W. Kenneth

2010-01-01

OBJECTIVE To minimize hypoglycemia in subjects with type 1 diabetes by automated glucagon delivery in a closed-loop insulin delivery system. RESEARCH DESIGN AND METHODS Adult subjects with type 1 diabetes underwent one closed-loop study with insulin plus placebo and one study with insulin plus glucagon, given at times of impending hypoglycemia. Seven subjects received glucagon using high-gain parameters, and six subjects received glucagon in a more prolonged manner using low-gain parameters. Blood glucose levels were measured every 10 min and insulin and glucagon infusions were adjusted every 5 min. All subjects received a portion of their usual premeal insulin after meal announcement. RESULTS Automated glucagon plus insulin delivery, compared with placebo plus insulin, significantly reduced time spent in the hypoglycemic range (15 ± 6 vs. 40 ± 10 min/day, P = 0.04). Compared with placebo, high-gain glucagon delivery reduced the frequency of hypoglycemic events (1.0 ± 0.6 vs. 2.1 ± 0.6 events/day, P = 0.01) and the need for carbohydrate treatment (1.4 ± 0.8 vs. 4.0 ± 1.4 treatments/day, P = 0.01). Glucagon given with low-gain parameters did not significantly reduce hypoglycemic event frequency (P = NS) but did reduce frequency of carbohydrate treatment (P = 0.05). CONCLUSIONS During closed-loop treatment in subjects with type 1 diabetes, high-gain pulses of glucagon decreased the frequency of hypoglycemia. Larger and longer-term studies will be required to assess the effect of ongoing glucagon treatment on overall glycemic control. PMID:20332355

Effects of human chromosome 12 on interactions between Tat and TAR of human immunodeficiency virus type 1.

PubMed Central

Alonso, A; Cujec, T P; Peterlin, B M

1994-01-01

Rates of transcriptions of the human immunodeficiency virus are greatly increased by the viral trans activator Tat. In vitro, Tat binds to the 5' bulge of the trans-activation response (TAR) RNA stem-loop, which is present in all viral transcripts. In human cells, the central loop in TAR and its cellular RNA-binding proteins are also critical for the function of Tat. Previously, we demonstrated that in rodent cells (CHO cells), but not in those which contain the human chromosome 12 (CHO12 cells), Tat-TAR interactions are compromised. In this study, we examined the roles of the bulge and loop in TAR in Tat trans activation in these cells. Whereas low levels of trans activation depended solely on interactions between Tat and the bulge in CHO cells, high levels of trans activation depended also on interactions between Tat and the loop in CHO12 cells. Since the TAR loop binding proteins in these two cell lines were identical and different from their human counterpart, the human chromosome 12 does not encode TAR loop binding proteins. In vivo binding competition studies with TAR decoys confirmed that the binding of Tat to TAR is more efficient in CHO12 cells. Thus, the protein(s) encoded on human chromosome 12 helps to tether Tat to TAR via its loop, which results in high levels of trans activation. Images PMID:8083988

Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1

PubMed Central

Pal, Gayatri; Paraz, Maria T.Z.; Kellogg, Douglas R.

2008-01-01

The Cdc25 phosphatase promotes entry into mitosis by removing cyclin-dependent kinase 1 (Cdk1) inhibitory phosphorylation. Previous work suggested that Cdc25 is activated by Cdk1 in a positive feedback loop promoting entry into mitosis; however, it has remained unclear how the feedback loop is initiated. To learn more about the mechanisms that regulate entry into mitosis, we have characterized the function and regulation of Mih1, the budding yeast homologue of Cdc25. We found that Mih1 is hyperphosphorylated early in the cell cycle and is dephosphorylated as cells enter mitosis. Casein kinase 1 is responsible for most of the hyperphosphorylation of Mih1, whereas protein phosphatase 2A associated with Cdc55 dephosphorylates Mih1. Cdk1 appears to directly phosphorylate Mih1 and is required for initiation of Mih1 dephosphorylation as cells enter mitosis. Collectively, these observations suggest that Mih1 regulation is achieved by a balance of opposing kinase and phosphatase activities. Because casein kinase 1 is associated with sites of polar growth, it may regulate Mih1 as part of a signaling mechanism that links successful completion of growth-related events to cell cycle progression. PMID:18316413

A Feedback Loop between Dynamin and Actin Recruitment during Clathrin-Mediated Endocytosis

PubMed Central

Taylor, Marcus J.; Lampe, Marko; Merrifield, Christien J.

2012-01-01

Clathrin-mediated endocytosis proceeds by a sequential series of reactions catalyzed by discrete sets of protein machinery. The final reaction in clathrin-mediated endocytosis is membrane scission, which is mediated by the large guanosine triophosphate hydrolase (GTPase) dynamin and which may involve the actin-dependent recruitment of N-terminal containing BIN/Amphiphysin/RVS domain containing (N-BAR) proteins. Optical microscopy has revealed a detailed picture of when and where particular protein types are recruited in the ∼20–30 s preceding scission. Nevertheless, the regulatory mechanisms and functions that underpin protein recruitment are not well understood. Here we used an optical assay to investigate the coordination and interdependencies between the recruitment of dynamin, the actin cytoskeleton, and N-BAR proteins to individual clathrin-mediated endocytic scission events. These measurements revealed that a feedback loop exists between dynamin and actin at sites of membrane scission. The kinetics of dynamin, actin, and N-BAR protein recruitment were modulated by dynamin GTPase activity. Conversely, acute ablation of actin dynamics using latrunculin-B led to a ∼50% decrease in the incidence of scission, an ∼50% decrease in the amplitude of dynamin recruitment, and abolished actin and N-BAR recruitment to scission events. Collectively these data suggest that dynamin, actin, and N-BAR proteins work cooperatively to efficiently catalyze membrane scission. Dynamin controls its own recruitment to scission events by modulating the kinetics of actin and N-BAR recruitment to sites of scission. Conversely actin serves as a dynamic scaffold that concentrates dynamin and N-BAR proteins at sites of scission. PMID:22505844

Deletion of loop fragment adjacent to active site diminishes the stability and activity of exo-inulinase.

PubMed

Arjomand, Maryam Rezaei; Habibi-Rezaei, Mehran; Ahmadian, Gholamreza; Hassanzadeh, Malihe; Karkhane, Ali Asghar; Asadifar, Mandana; Amanlou, Massoud

2016-11-01

Inulinases are classified as hydrolases and widely used in the food and medical industries. Here, we report the deletion of a six-membered adjacent active site loop fragment ( 74 YGSDVT 79 sequence) from third Ω-loop of the exo-inulinase containing aspartate residue from Aspergillus niger to study its structural and functional importance. Site-directed mutagenesis was used to create the mutant of the exo-inulinase (Δ6SL). To investigate the stability of the region spanning this loop, MD simulations were performed 80ns for 20-85 residues. Molecular docking was performed to compare the interactions in the active sites of enzymes with fructose as a ligand. Accordingly, the functional thermostability of the exo-inulinase was significantly decreased upon loop fragment deletion. Evaluation of the kinetics parameters (V max , K m , k cat and, k cat /K m ) and activation energy (E a ) of the catalysis of enzymes indicated the importance of the deleted sequence on the catalytic performance of the enzyme. In conclusion, six-membered adjacent active site loop fragment not only plays a crucial role in the stability of the enzyme, but also it involves in the enzyme catalysis through lowering the activation energy of the catalysis and effective improving the catalytic performance. Copyright © 2016. Published by Elsevier B.V.

Time-frequency analysis of the EEG mu rhythm as a measure of sensorimotor integration in the later stages of swallowing.

PubMed

Cuellar, M; Harkrider, A W; Jenson, D; Thornton, D; Bowers, A; Saltuklaroglu, T

2016-07-01

Electroencephalography (EEG) was used to map the temporal dynamics of sensorimotor integration relative to the strength and timing of muscular activity during swallowing. 64-channel EEG data and surface electromyographic (sEMG) data were recorded from 25 neurologically-healthy adults during swallowing and tongue-tapping. Events were demarcated so that sensorimotor activity primarily from the pharyngeal and esophageal phases of swallowing could be compared to activity resulting from tongue tapping. Independent component analysis identified bilateral clusters of sensorimotor mu components localized to the premotor and primary motor cortices as well as an infrahyoid myogenic cluster. Subsequent event-related spectral perturbations (ERSP) analyses showed event-related desynchronization (ERD) in the spectral power in the alpha (8-13Hz) and beta (15-25Hz) frequency bands of the mu clusters in both tasks. Mu ERD was stronger during swallowing when compared to tongue tapping (pFDR<.05) and the differences in sensorimotor processing between conditions was greater in the right hemisphere than the left, suggesting stronger right hemisphere lateralization for swallowing than tongue-tapping. Mu activity was interpreted as representing a normal feed forward and feedback driven sensorimotor loop during the later stages of swallowing. Results support further use of this novel neuroimaging technique to concurrently map neural and muscle activity during swallowing in clinical populations using EEG. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The Significance of Ras Activity in Pancreatic Cancer Initiation.

PubMed

Logsdon, Craig D; Lu, Weiqin

2016-01-01

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Ras(mt). Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Ras(mt) is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Ras(mt) activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Ras(mt). Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Ras(mt) activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease.

Assessing catchment connectivity using hysteretic loops

NASA Astrophysics Data System (ADS)

Davis, Jason; Masselink, Rens; Goni, Mikel; Gimenez, Rafael; Casali, Javier; Seeger, Manuel; Keesstra, Saskia

2017-04-01

Storm events mobilize large proportions of sediments in catchment systems. Therefore understanding catchment sediment dynamics throughout the continuity of storms and how initial catchment states act as controls on the transport of sediment to catchment outlets is important for effective catchment management. Sediment connectivity is a concept which can explain the origin, pathways and sinks of sediments within catchments (Baartman et al., 2013; Parsons et al., 2015; Masselink et al., 2016a,b; Mekonnen et al., 2016). However, sediment connectivity alone does not provide a practicable mechanism by which the catchment's initial state - and thus the location of entrained sediment in the sediment transport cascade - can be characterized. Studying the dynamic relationship between water discharge (Q) and suspended sediment (SS) at the catchment outlet can provide a valuable research tool to infer the likely source areas and flow pathways contributing to sediment transport because the relationship can be characterized by predictable hysteresis patterns. Hysteresis is observed when the sediment concentration associated with a certain flow rate is different depending on the direction in which the analysis is performed - towards the increase or towards the diminution of the flow. However, the complexity of the phenomena and factors which determine the hysteresis make its interpretation ambiguous. Previous work has described various types of hysteretic loops as well as the cause for the shape of the loop, mainly pointing to the origin of the sediments. The data set for this study comes from four experimental watersheds in Navarre (Spain), owned and maintained by the Government of Navarre. These experimental watersheds have been monitored and studied since 1996 (La Tejería and Latxaga) and 2001 (Oskotz principal and Oskotz woodland). La Tejería and Latxaga watersheds are similar to each other regarding size (approximately 200 ha), geology (marls and sandstones), soils (fine texture topsoil), climate (humid sub Mediterranean) and land use (80-90% cultivated with winter grain crops). Ozkotz principal (ca.1,700 ha) is covered with forest and pasture (cattle-breeding); while Oskotz woodland (ca. 500 ha), a sub-watershed of the Oskotz principal, is almost completely covered with forest. The predominant climate in the Oskotz catchments sub-Atlantic. Furthermore, antecedent conditions and event characteristics were analysed. The loops were compared quantitatively and qualitatively between catchments for similar events and within the catchments for events with different characteristics. In this study, several measures to objectively classify hysteresis loops in an automated way were developed. These were consecutively used to classify several hundreds of loops from several agricultural catchments in Northern Spain. These loop characteristics were compared to event specific characteristics such as antecedent precipitation, time of year, and precipitation intensity, duration and total. The combination of hysteresis loops and variables influencing connectivity can then tell something about the sources of sediments for different events and catchments. References Baartman, J.E.M., Masselink, R.H., Keesstra, S.D., Temme, A.J.A.M., 2013. Linking landscape morphological complexity and sediment connectivity. Earth Surface Processes and Landforms 38: 1457-1471. Masselink RJH, Heckmann T, Temme AJAM, Anders NS, Gooren HPA, Keesstra SD. 2016. A network theory approach for a better understanding of overland flow connectivity. Hydrological Processes. DOI: 10.1002/hyp.10993 Masselink, R.J.H., Keesstra, S.D., Temme, A.J.A.M., Seeger, M., Giménez, R., Casalí, J., 2016. Modelling Discharge and Sediment Yield at Catchment Scale Using Connectivity Components. Land Degradation and Development 27: 933-945, DOI: 10.1002/ldr.2512 Mekonnen, M., Keesstra, S.D., Baartman, J.E.M., Stroosnijder, L., Maroulis, J., Reducing sediment connectivity through man-made and natural sediment sinks in the Minizr catchment, north-west Ethiopia. Accepted to Land Degradation and Development. Parsons A.J., Bracken L., Peoppl , R., Wainwright J., Keesstra, S.D., 2015. Editorial: Introduction to special issue on connectivity in water and sediment dynamics. In press in Earth Surface Processes and Landforms. DOI: 10.1002/esp.3714

Propagating wave in active region-loops, located over the solar disk observed by the Interface Region Imaging Spectrograph

NASA Astrophysics Data System (ADS)

Zhang, B.; Hou, Y. J.; Zhang, J.

2018-03-01

Aims: We aim to ascertain the physical parameters of a propagating wave over the solar disk detected by the Interface Region Imaging Spectrograph (IRIS). Methods: Using imaging data from the IRIS and the Solar Dynamic Observatory (SDO), we tracked bright spots to determine the parameters of a propagating transverse wave in active region (AR) loops triggered by activation of a filament. Deriving the Doppler velocity of Si IV line from spectral observations of IRIS, we have determined the rotating directions of active region loops which are relevant to the wave. Results: On 2015 December 19, a filament was located on the polarity inversion line of the NOAA AR 12470. The filament was activated and then caused a C1.1 two-ribbon flare. Between the flare ribbons, two rotation motions of a set of bright loops were observed to appear in turn with opposite directions. Following the end of the second rotation, a propagating wave and an associated transverse oscillation were detected in these bright loops. In 1400 Å channel, there was bright material flowing along the loops in a wave-like manner, with a period of 128 s and a mean amplitude of 880 km. For the transverse oscillation, we tracked a given loop and determine the transverse positions of the tracking loop in a limited longitudinal range. In both of 1400 Å and 171 Å channels, approximately four periods are distinguished during the transverse oscillation. The mean period of the oscillation is estimated as 143 s and the displacement amplitude as between 1370 km and 690 km. We interpret these oscillations as a propagating kink wave and obtain its speed of 1400 km s-1. Conclusions: Our observations reveal that a flare associated with filament activation could trigger a kink propagating wave in active region loops over the solar disk. Movies associated to Figs. 1-4 are available at http://https://www.aanda.org

Reconstructing a missing link in the evolution of a recently diverged phosphotriesterase by active-site loop remodeling.

PubMed

Afriat-Jurnou, Livnat; Jackson, Colin J; Tawfik, Dan S

2012-08-07

Only decades after the introduction of organophosphate pesticides, bacterial phosphotriesterases (PTEs) have evolved to catalyze their degradation with remarkable efficiency. Their closest known relatives, lactonases, with promiscuous phosphotriasterase activity, dubbed PTE-like lactonases (PLLs), share only 30% sequence identity and also differ in the configuration of their active-site loops. PTE was therefore presumed to have evolved from a yet unknown PLL whose primary activity was the hydrolysis of quorum sensing homoserine lactones (HSLs) (Afriat et al. (2006) Biochemistry 45, 13677-13686). However, how PTEs diverged from this presumed PLL remains a mystery. In this study we investigated loop remodeling as a means of reconstructing a homoserine lactonase ancestor that relates to PTE by few mutational steps. Although, in nature, loop remodeling is a common mechanism of divergence of enzymatic functions, reproducing this process in the laboratory is a challenge. Structural and phylogenetic analyses enabled us to remodel one of PTE's active-site loops into a PLL-like configuration. A deletion in loop 7, combined with an adjacent, highly epistatic, point mutation led to the emergence of an HSLase activity that is undetectable in PTE (k(cat)/K(M) values of up to 2 × 10(4)). The appearance of the HSLase activity was accompanied by only a minor decrease in PTE's paraoxonase activity. This specificity change demonstrates the potential role of bifunctional intermediates in the divergence of new enzymatic functions and highlights the critical contribution of loop remodeling to the rapid divergence of new enzyme functions.

A conserved loop-wedge motif moderates reaction site search and recognition by FEN1.

PubMed

Thompson, Mark J; Gotham, Victoria J B; Ciani, Barbara; Grasby, Jane A

2018-06-07

DNA replication and repair frequently involve intermediate two-way junction structures with overhangs, or flaps, that must be promptly removed; a task performed by the essential enzyme flap endonuclease 1 (FEN1). We demonstrate a functional relationship between two intrinsically disordered regions of the FEN1 protein, which recognize opposing sides of the junction and order in response to the requisite substrate. Our results inform a model in which short-range translocation of FEN1 on DNA facilitates search for the annealed 3'-terminus of a primer strand, which is recognized by breaking the terminal base pair to generate a substrate with a single nucleotide 3'-flap. This recognition event allosterically signals hydrolytic removal of the 5'-flap through reaction in the opposing junction duplex, by controlling access of the scissile phosphate diester to the active site. The recognition process relies on a highly-conserved 'wedge' residue located on a mobile loop that orders to bind the newly-unpaired base. The unanticipated 'loop-wedge' mechanism exerts control over substrate selection, rate of reaction and reaction site precision, and shares features with other enzymes that recognize irregular DNA structures. These new findings reveal how FEN1 precisely couples 3'-flap verification to function.

Robust Brain-Machine Interface Design Using Optimal Feedback Control Modeling and Adaptive Point Process Filtering

PubMed Central

Carmena, Jose M.

2016-01-01

Much progress has been made in brain-machine interfaces (BMI) using decoders such as Kalman filters and finding their parameters with closed-loop decoder adaptation (CLDA). However, current decoders do not model the spikes directly, and hence may limit the processing time-scale of BMI control and adaptation. Moreover, while specialized CLDA techniques for intention estimation and assisted training exist, a unified and systematic CLDA framework that generalizes across different setups is lacking. Here we develop a novel closed-loop BMI training architecture that allows for processing, control, and adaptation using spike events, enables robust control and extends to various tasks. Moreover, we develop a unified control-theoretic CLDA framework within which intention estimation, assisted training, and adaptation are performed. The architecture incorporates an infinite-horizon optimal feedback-control (OFC) model of the brain’s behavior in closed-loop BMI control, and a point process model of spikes. The OFC model infers the user’s motor intention during CLDA—a process termed intention estimation. OFC is also used to design an autonomous and dynamic assisted training technique. The point process model allows for neural processing, control and decoder adaptation with every spike event and at a faster time-scale than current decoders; it also enables dynamic spike-event-based parameter adaptation unlike current CLDA methods that use batch-based adaptation on much slower adaptation time-scales. We conducted closed-loop experiments in a non-human primate over tens of days to dissociate the effects of these novel CLDA components. The OFC intention estimation improved BMI performance compared with current intention estimation techniques. OFC assisted training allowed the subject to consistently achieve proficient control. Spike-event-based adaptation resulted in faster and more consistent performance convergence compared with batch-based methods, and was robust to parameter initialization. Finally, the architecture extended control to tasks beyond those used for CLDA training. These results have significant implications towards the development of clinically-viable neuroprosthetics. PMID:27035820

System and method of designing models in a feedback loop

DOEpatents

Gosink, Luke C.; Pulsipher, Trenton C.; Sego, Landon H.

2017-02-14

A method and system for designing models is disclosed. The method includes selecting a plurality of models for modeling a common event of interest. The method further includes aggregating the results of the models and analyzing each model compared to the aggregate result to obtain comparative information. The method also includes providing the information back to the plurality of models to design more accurate models through a feedback loop.

Thermal responses in a coronal loop maintained by wave heating mechanisms

NASA Astrophysics Data System (ADS)

Matsumoto, Takuma

2018-05-01

A full 3-dimensional compressible magnetohydrodynamic (MHD) simulation is conducted to investigate the thermal responses of a coronal loop to the dynamic dissipation processes of MHD waves. When the foot points of the loop are randomly and continuously forced, the MHD waves become excited and propagate upward. Then, 1-MK temperature corona is produced naturally as the wave energy dissipates. The excited wave packets become non-linear just above the magnetic canopy, and the wave energy cascades into smaller spatial scales. Moreover, collisions between counter-propagating Alfvén wave packets increase the heating rate, resulting in impulsive temperature increases. Our model demonstrates that the heating events in the wave-heated loops can be nanoflare-like in the sense that they are spatially localized and temporally intermittent.

Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

PubMed

Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

2004-03-01

By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

Effect of proline and glycine residues on dynamics and barriers of loop formation in polypeptide chains.

PubMed

Krieger, Florian; Möglich, Andreas; Kiefhaber, Thomas

2005-03-16

Glycine and proline residues are frequently found in turn and loop structures of proteins and are believed to play an important role during chain compaction early in folding. We investigated their effect on the dynamics of intrachain loop formation in various unstructured polypeptide chains. Loop formation is significantly slower around trans prolyl peptide bonds and faster around glycine residues compared to any other amino acid. However, short loops are formed fastest around cis prolyl bonds with a time constant of 6 ns for end-to-end contact formation in a four-residue loop. Formation of short loops encounters activation energies in the range of 15 to 30 kJ/mol. The altered dynamics around glycine and trans prolyl bonds can be mainly ascribed to their effects on the activation energy. The fast dynamics around cis prolyl bonds, in contrast, originate in a higher Arrhenius pre-exponential factor, which compensates for an increased activation energy for loop formation compared to trans isomers. All-atom simulations of proline-containing peptides indicate that the conformational space for cis prolyl isomers is largely restricted compared to trans isomers. This leads to decreased average end-to-end distances and to a smaller loss in conformational entropy upon loop formation in cis isomers. The results further show that glycine and proline residues only influence formation of short loops containing between 2 and 10 residues, which is the typical loop size in native proteins. Formation of larger loops is not affected by the presence of a single glycine or proline residue.

Varietal Loops

NASA Image and Video Library

2016-09-15

A series of active regions stretched along the right side of the sun exhibited a wide variety of loops cascading above them (Sept. 12-14, 2016). The active region near the center has tightly coiled loops, while the region rotating over the right edge has some elongated and some very stretched loops above it. The loops are actually charged particles spiraling along magnetic field lines, observed here in a wavelength of extreme ultraviolet light. Near the middle of the video the Earth quickly passes in front of a portion of the sun as viewed by SDO. http://photojournal.jpl.nasa.gov/catalog/PIA16997

The Twist Limit for Bipolar Active Regions

NASA Technical Reports Server (NTRS)

Moore, Ron; Falconer, David; Gary, Allen

2008-01-01

We present new evidence that further supports the standard idea that active regions are emerged magnetic-flux-rope omega loops. When the axial magnetic twist of a cylindrical flux rope exceeds a critical amount, the flux rope becomes unstable to kinking, and the excess axial twist is converted into writhe twist by the kinking. This suggests that, if active regions are emerged omega loops, then (1) no active region should have magnetic twist much above the limit set by kinking, (2) active regions having twist near the limit should often arise from kinked omega loops, and (3) since active regions having large delta sunspots are outstandingly twisted, these arise from kinked omega loops and should have twist near the limit for kinking. From each of 36 vector magnetograms of bipolar active regions, we have measured (1) the total flux of the vertical field above 100 G, (2) the area covered by this flux, and (3) the net electric current that arches over the polarity inversion line. These three quantities yield an estimate of the axial magnetic twist in a simple model cylindrical flux rope that corresponds to the top of the active region s hypothetical omega loop prior to emergence. In all 36 cases, the estimated twist is below the critical limit for kinking. The 11 most twisted active regions (1) have estimated twist within a factor of approx.3 of the limit, and (2) include all of our 6 active regions having large delta sunspots. Thus, our observed twist limit for bipolar active regions is in good accord with active regions being emerged omega loops.

Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase

PubMed Central

Helmstaedt, Kerstin; Heinrich, Gabriele; Lipscomb, William N.; Braus, Gerhard H.

2002-01-01

The yeast chorismate mutase is regulated by tyrosine as feedback inhibitor and tryptophan as crosspathway activator. The monomer consists of a catalytic and a regulatory domain covalently linked by the loop L220s (212–226), which functions as a molecular hinge. Two monomers form the active dimeric enzyme stabilized by hydrophobic interactions in the vicinity of loop L220s. The role of loop L220s and its environment for enzyme regulation, dimerization, and stability was analyzed. Substitution of yeast loop L220s in place of the homologous loop from the corresponding and similarly regulated Aspergillus enzyme (and the reverse substitution) changed tyrosine inhibition to activation. Yeast loop L220s substituted into the Aspergillus enzyme resulted in a tryptophan-inhibitable enzyme. Monomeric yeast chorismate mutases could be generated by substituting two hydrophobic residues in and near the hinge region. The resulting Thr-212→Asp–Phe-28→Asp enzyme was as stable as wild type, but lost allosteric regulation and showed reduced catalytic activity. These results underline the crucial role of this molecular hinge for inhibition, activation, quaternary structure, and stability of yeast chorismate mutase. PMID:11997452

Manipulation of the extrastriate frontal loop can resolve visual disability in blindsight patients.

PubMed

Badgaiyan, Rajendra D

2012-12-01

Patients with blindsight are not consciously aware of visual stimuli in the affected field of vision but retain nonconscious perception. This disability can be resolved if nonconsciously perceived information can be brought to their conscious awareness. It can be accomplished by manipulating neural network of visual awareness. To understand this network, we studied the pattern of cortical activity elicited during processing of visual stimuli with or without conscious awareness. The analysis indicated that a re-entrant signaling loop between the area V3A (located in the extrastriate cortex) and the frontal cortex is critical for processing conscious awareness. The loop is activated by visual signals relayed in the primary visual cortex, which is damaged in blindsight patients. Because of the damage, V3A-frontal loop is not activated and the signals are not processed for conscious awareness. These patients however continue to receive visual signals through the lateral geniculate nucleus. Since these signals do not activate the V3A-frontal loop, the stimuli are not consciously perceived. If visual input from the lateral geniculate nucleus is appropriately manipulated and made to activate the V3A-frontal loop, blindsight patients can regain conscious vision. Published by Elsevier Ltd.

Invisibility of Solar Active Region Umbra-to-Umbra Coronal Loops: New Evidence that Magnetoconvection Drives Solar-Stellar Coronal Heating

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Panesar, Navdeep K.; Moore, Ronald L.; Winebarger, Amy R.

2017-01-01

Coronal heating generally increases with increasing magnetic field strength: the EUV/X-ray corona in active regions is 10--100 times more luminous and 2--4 times hotter than that in quiet regions and coronal holes, which are heated to only about 1.5 MK, and have fields that are 10--100 times weaker than that in active regions. From a comparison of a nonlinear force-free model of the three-dimensional active region coronal field to observed extreme-ultraviolet loops, we find that (1) umbra-to-umbra coronal loops, despite being rooted in the strongest magnetic flux, are invisible, and (2) the brightest loops have one foot in an umbra or penumbra and the other foot in another sunspot's penumbra or in unipolar or mixed-polarity plage. The invisibility of umbra-to-umbra loops is new evidence that magnetoconvection drives solar-stellar coronal heating: evidently, the strong umbral field at both ends quenches the magnetoconvection and hence the heating. Our results from EUV observations and nonlinear force-free modeling of coronal magnetic field imply that, for any coronal loop on the Sun or on any other convective star, as long as the field can be braided by convection in at least one loop foot, the stronger the field in the loop, the stronger the coronal heating.

Fundamental Characteristics of AAA+ Protein Family Structure and Function

PubMed Central

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

LOOP: Linking Outcomes to Organizational Planning, First Quarterly Report: 25 School Board Priorities.

ERIC Educational Resources Information Center

Ligon, Glynn; Wicker, Maria L. R.

The Austin Independent School District Superintendent of Schools required a process for monitoring district activities. The Office of Research and Evaluation developed LOOP (Linking Outcomes to Organizational Planning). LOOP is a management information system through which progress in a number of activities within the school system may be…

Flares and Their Underlying Magnetic Complexity

NASA Astrophysics Data System (ADS)

Engell, Alexander J.; Siarkowski, Marek; Gryciuk, Magda; Sylwester, Janusz; Sylwester, Barbara; Golub, Leon; Korreck, Kelly; Cirtain, Jonathan

2011-01-01

SphinX (Solar PHotometer IN X-rays), a full-disk-integrated spectrometer, observed 137 flare-like/transient events with active region (AR) 11024 being the only AR on disk. The Hinode X-Ray Telescope (XRT) and Solar Optical Telescope observe 67 of these events and identified their location from 12:00 UT on July 3 through 24:00 UT 2009 July 7. We find that the predominant mechanisms for flares observed by XRT are (1) flux cancellation and (2) the shearing of underlying magnetic elements. Point- and cusp-like flare morphologies seen by XRT all occur in a magnetic environment where one polarity is impeded by the opposite polarity and vice versa, forcing the flux cancellation process. The shearing is either caused by flux emergence at the center of the AR and separation of polarities along a neutral line or by individual magnetic elements having a rotational motion. Both mechanisms are observed to contribute to single- and multiple-loop flares. We observe that most loop flares occur along a large portion of a polarity inversion line. Point- and cusp-like flares become more infrequent as the AR becomes organized with separation of the positive and negative polarities. SphinX, which allows us to identify when these flares occur, provides us with a statistically significant temperature and emission scaling law for A and B class flares: EM = 6.1 × 1033 T 1.9±0.1.

MacA is a second cytochrome c peroxidase of Geobacter sulfurreducens.

PubMed

Seidel, Julian; Hoffmann, Maren; Ellis, Katie E; Seidel, Antonia; Spatzal, Thomas; Gerhardt, Stefan; Elliott, Sean J; Einsle, Oliver

2012-04-03

The metal-reducing δ-proteobacterium Geobacter sulfurreducens produces a large number of c-type cytochromes, many of which have been implicated in the transfer of electrons to insoluble metal oxides. Among these, the dihemic MacA was assigned a central role. Here we have produced G. sulfurreducens MacA by recombinant expression in Escherichia coli and have solved its three-dimensional structure in three different oxidation states. Sequence comparisons group MacA into the family of diheme cytochrome c peroxidases, and the protein indeed showed hydrogen peroxide reductase activity with ABTS(-2) as an electron donor. The observed K(M) was 38.5 ± 3.7 μM H(2)O(2) and v(max) was 0.78 ± 0.03 μmol of H(2)O(2)·min(-1)·mg(-1), resulting in a turnover number k(cat) = 0.46 · s(-1). In contrast, no Fe(III) reductase activity was observed. MacA was found to display electrochemical properties similar to other bacterial diheme peroxidases, in addition to the ability to electrochemically mediate electron transfer to the soluble cytochrome PpcA. Differences in activity between CcpA and MacA can be rationalized with structural variations in one of the three loop regions, loop 2, that undergoes conformational changes during reductive activation of the enzyme. This loop is adjacent to the active site heme and forms an open loop structure rather than a more rigid helix as in CcpA. For the activation of the protein, the loop has to displace the distal ligand to the active site heme, H93, in loop 1. A H93G variant showed an unexpected formation of a helix in loop 2 and disorder in loop 1, while a M297H variant that altered the properties of the electron transfer heme abolished reductive activation.

MacA is a Second Cytochrome c Peroxidase of Geobacter sulfurreducens

PubMed Central

Seidel, Julian; Hoffmann, Maren; Ellis, Katie E.; Seidel, Antonia; Spatzal, Thomas; Gerhardt, Stefan; Elliott, Sean J.

2012-01-01

The metal-reducing δ-proteobacterium Geobacter sulfurreducens produces a large number of c-type cytochromes, many of which have been implicated in the transfer of electrons to insoluble metal oxides. Among these, the dihemic MacA was assigned a central role. Here we have produced G. sulfurreducens MacA by recombinant expression in Escherichia coli and have solved its three-dimensional structure in three different oxidation states. Sequence comparisons group MacA into the family of diheme cytochrome c peroxidases, and the protein indeed showed hydrogen peroxide reductase activity with ABTS2– as an electron donor. The observed KM was 38.5 ± 3.7 μM H2O2 and vmax was 0.78 ± 0.03 μmol H2O2·min–1·mg–1, resulting in a turnover number kcat = 0.46 · s–1. In contrast, no Fe(III) reductase activity was observed. MacA was found to display similar electrochemical properties to other bacterial diheme peroxidases, in additional to the ability to electrochemically mediate electron transfer to the soluble cytochrome PpcA. Differences in activity between CcpA and MacA can be rationalized with structural variations in one of the three loop regions, loop 2, that undergo conformational changes during reductive activation of the enzyme. This loop is adjacent to the active site heme and forms an open loop structure rather than a more rigid helix as in CcpA. For the activation of the protein the loop has to displace the distal ligand to the active site heme, H93, in loop 1. A H93G variant showed an unexpected formation of a helix in loop 2 and disorder in loop 1, while a M297H variant that altered the properties of the electron transfer heme abolished reductive activation. PMID:22417533

Capillary Limit in a Loop Heat Pipe with Dual Evaporators

NASA Technical Reports Server (NTRS)

Ku, Jentung; Birur, Gajanana; Obenschain, Arthur F. (Technical Monitor)

2002-01-01

This paper describes a study on the capillary limit of a loop heat pipe (LHP) with two evaporators and two condensers. Both theoretical analysis and experimental investigation are conducted. Tests include heat load to one evaporator only, even heat loads to both evaporators and uneven heat load to both evaporators. Results show that after the capillary limit is exceeded, vapor will penetrate through the wick of the weaker evaporator and the compensation chamber (CC) of that evaporator will control the loop operating temperature regardless of which CC has been in control prior to the event Because the evaporator can tolerate vapor bubbles, the loop may continue to work and reach a new steady state at a higher operating temperature. The loop may even function with a modest increase in the heat load past the capillary limit With a heat load to only one evaporator, the capillary limit can be identified by rapid increases in the operating temperature and in the temperature difference between the evaporator and the CC. However, it is more difficult to tell when the capillary limit is exceeded if heat loads are applied to both evaporators. In all cases, the loop can recover by reducing the heat load to the loop.

Structure-function analyses of human kallikrein-related peptidase 2 establish the 99-loop as master regulator of activity.

PubMed

Skala, Wolfgang; Utzschneider, Daniel T; Magdolen, Viktor; Debela, Mekdes; Guo, Shihui; Craik, Charles S; Brandstetter, Hans; Goettig, Peter

2014-12-05

Human kallikrein-related peptidase 2 (KLK2) is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the "classical" KLKs 1-3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 Å crystal structures of two KLK2-small molecule inhibitor complexes. In both structures discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn(2+) concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn(2+), which located the Zn(2+) binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family the 99-, 148-, and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure-Function Analyses of Human Kallikrein-related Peptidase 2 Establish the 99-Loop as Master Regulator of Activity*

PubMed Central

Skala, Wolfgang; Utzschneider, Daniel T.; Magdolen, Viktor; Debela, Mekdes; Guo, Shihui; Craik, Charles S.; Brandstetter, Hans; Goettig, Peter

2014-01-01

Human kallikrein-related peptidase 2 (KLK2) is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the “classical” KLKs 1–3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 Å crystal structures of two KLK2-small molecule inhibitor complexes. In both structures discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn2+ concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn2+, which located the Zn2+ binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family the 99-, 148-, and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. PMID:25326387

Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

PubMed Central

Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

2014-01-01

G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599

Resolving Off-Nominal Situations in Schedule-Based Terminal Area Operations: Results from a Human-in-the-Loop Simulation

NASA Technical Reports Server (NTRS)

Mercer, Joey; Callantine, Todd; Martin, Lynne

2012-01-01

A recent human-in-the-loop simulation in the Airspace Operations Laboratory (AOL) at NASA's Ames Research Center investigated the robustness of Controller-Managed Spacing (CMS) operations. CMS refers to AOL-developed controller tools and procedures for enabling arrivals to conduct efficient Optimized Profile Descents with sustained high throughput. The simulation provided a rich data set for examining how a traffic management supervisor and terminal-area controller participants used the CMS tools and coordinated to respond to off-nominal events. This paper proposes quantitative measures for characterizing the participants responses. Case studies of go-around events, replicated during the simulation, provide insights into the strategies employed and the role the CMS tools played in supporting them.

Laser Safety Method For Duplex Open Loop Parallel Optical Link

DOEpatents

Baumgartner, Steven John; Hedin, Daniel Scott; Paschal, Matthew James

2003-12-02

A method and apparatus are provided to ensure that laser optical power does not exceed a "safe" level in an open loop parallel optical link in the event that a fiber optic ribbon cable is broken or otherwise severed. A duplex parallel optical link includes a transmitter and receiver pair and a fiber optic ribbon that includes a designated number of channels that cannot be split. The duplex transceiver includes a corresponding transmitter and receiver that are physically attached to each other and cannot be detached therefrom, so as to ensure safe, laser optical power in the event that the fiber optic ribbon cable is broken or severed. Safe optical power is ensured by redundant current and voltage safety checks.

Dynamic Consequences of Mutation of Tryptophan 215 in Thrombin.

PubMed

Peacock, Riley B; Davis, Jessie R; Markwick, Phineus R L; Komives, Elizabeth A

2018-05-08

Thrombin normally cleaves fibrinogen to promote coagulation; however, binding of thrombomodulin to thrombin switches the specificity of thrombin toward protein C, triggering the anticoagulation pathway. The W215A thrombin mutant was reported to have decreased activity toward fibrinogen without significant loss of activity toward protein C. To understand how mutation of Trp215 may alter thrombin specificity, hydrogen-deuterium exchange experiments (HDXMS), accelerated molecular dynamics (AMD) simulations, and activity assays were carried out to compare the dynamics of Trp215 mutants with those of wild type (WT) thrombin. Variation in NaCl concentration had no detectable effect on the sodium-binding (220s CT ) loop, but appeared to affect other surface loops. Trp215 mutants showed significant increases in amide exchange in the 170s CT loop consistent with a loss of H-bonding in this loop identified by the AMD simulations. The W215A thrombin showed increased amide exchange in the 220s CT loop and in the N-terminus of the heavy chain. The AMD simulations showed that a transient conformation of the W215A thrombin has a distorted catalytic triad. HDXMS experiments revealed that mutation of Phe227, which engages in a π-stacking interaction with Trp215, also caused significantly increased amide exchange in the 170s CT loop. Activity assays showed that only the F227V mutant had wild type catalytic activity, whereas all other mutants showed markedly lower activity. Taken together, the results explain the reduced pro-coagulant activity of the W215A mutant and demonstrate the allosteric connection between Trp215, the sodium-binding loop, and the active site.

Chromospheric counterparts of solar transition region unresolved fine structure loops

NASA Astrophysics Data System (ADS)

Pereira, Tiago M. D.; Rouppe van der Voort, Luc; Hansteen, Viggo H.; De Pontieu, Bart

2018-04-01

Low-lying loops have been discovered at the solar limb in transition region temperatures by the Interface Region Imaging Spectrograph (IRIS). They do not appear to reach coronal temperatures, and it has been suggested that they are the long-predicted unresolved fine structures (UFS). These loops are dynamic and believed to be visible during both heating and cooling phases. Making use of coordinated observations between IRIS and the Swedish 1-m Solar Telescope, we study how these loops impact the solar chromosphere. We show for the first time that there is indeed a chromospheric signal of these loops, seen mostly in the form of strong Doppler shifts and a conspicuous lack of chromospheric heating. In addition, we find that several instances have a inverse Y-shaped jet just above the loop, suggesting that magnetic reconnection is driving these events. Our observations add several puzzling details to the current knowledge of these newly discovered structures; this new information must be considered in theoretical models. Two movies associated to Fig. 1 are available at http://https://www.aanda.org

Modelling machine ensembles with discrete event dynamical system theory

NASA Technical Reports Server (NTRS)

Hunter, Dan

1990-01-01

Discrete Event Dynamical System (DEDS) theory can be utilized as a control strategy for future complex machine ensembles that will be required for in-space construction. The control strategy involves orchestrating a set of interactive submachines to perform a set of tasks for a given set of constraints such as minimum time, minimum energy, or maximum machine utilization. Machine ensembles can be hierarchically modeled as a global model that combines the operations of the individual submachines. These submachines are represented in the global model as local models. Local models, from the perspective of DEDS theory , are described by the following: a set of system and transition states, an event alphabet that portrays actions that takes a submachine from one state to another, an initial system state, a partial function that maps the current state and event alphabet to the next state, and the time required for the event to occur. Each submachine in the machine ensemble is presented by a unique local model. The global model combines the local models such that the local models can operate in parallel under the additional logistic and physical constraints due to submachine interactions. The global model is constructed from the states, events, event functions, and timing requirements of the local models. Supervisory control can be implemented in the global model by various methods such as task scheduling (open-loop control) or implementing a feedback DEDS controller (closed-loop control).

Neutron activation analysis system

DOEpatents

Taylor, M.C.; Rhodes, J.R.

1973-12-25

A neutron activation analysis system for monitoring a generally fluid media, such as slurries, solutions, and fluidized powders, including two separate conduit loops for circulating fluid samples within the range of radiation sources and detectors is described. Associated with the first loop is a neutron source that emits s high flux of slow and thermal neutrons. The second loop employs a fast neutron source, the flux from which is substantially free of thermal neutrons. Adjacent to both loops are gamma counters for spectrographic determination of the fluid constituents. Other gsmma sources and detectors are arranged across a portion of each loop for deterMining the fluid density. (Official Gazette)

A tiny event producing an interplanetary type III burst

NASA Astrophysics Data System (ADS)

Alissandrakis, C. E.; Nindos, A.; Patsourakos, S.; Kontogeorgos, A.; Tsitsipis, P.

2015-10-01

Aims: We investigate the conditions under which small-scale energy release events in the low corona gave rise to strong interplanetary (IP) type III bursts. Methods: We analyzed observations of three tiny events, detected by the Nançay Radio Heliograph (NRH), two of which produced IP type III bursts. We took advantage of the NRH positioning information and of the high cadence of AIA/SDO data to identify the associated extreme-UV (EUV) emissions. We measured positions and time profiles of the metric and EUV sources. Results: We found that the EUV events that produced IP type III bursts were located near a coronal hole boundary, while the one that did not was located in a closed magnetic field region. In all three cases tiny flaring loops were involved, without any associated mass eruption. In the best observed case, the radio emission at the highest frequency (435 MHz) was displaced by ~55'' with respect to the small flaring loop. The metric type III emission shows a complex structure in space and in time, indicative of multiple electron beams, despite the low intensity of the events. From the combined analysis of dynamic spectra and NRH images, we derived the electron beam velocity as well as the height, ambient plasma temperature, and density at the level of formation of the 160 MHz emission. From the analysis of the differential emission measure derived from the AIA images, we found that the first evidence of energy release was at the footpoints, and this was followed by the development of flaring loops and subsequent cooling. Conclusions: Even small energy release events can accelerate enough electrons to give rise to powerful IP type III bursts. The proximity of the electron acceleration site to open magnetic field lines facilitates the escape of the electrons into the interplanetary space. The offset between the site of energy release and the metric type III location warrants further investigation. The movie is available in electronic form at http://www.aanda.org

Posttest examination of Sodium Loop Safety Facility experiments. [LMFBR

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

Holland, J.W.

In-reactor, safety experiments performed in the Sodium Loop Safety Facility (SLSF) rely on comprehensive posttest examinations (PTE) to characterize the postirradiation condition of the cladding, fuel, and other test-subassembly components. PTE information and on-line instrumentation data, are analyzed to identify the sequence of events and the severity of the accident for each experiment. Following in-reactor experimentation, the SLSF loop and test assembly are transported to the Hot Fuel Examination Facility (HFEF) for initial disassembly. Goals of the HFEF-phase of the PTE are to retrieve the fuel bundle by dismantling the loop and withdrawing the test assembly, to assess the macro-conditionmore » of the fuel bundle by nondestructive examination techniques, and to prepare the fuel bundle for shipment to the Alpha-Gamma Hot Cell Facility (AGHCF) at Argonne National Laboratory.« less

Scattering of Cosmic Strings by Black Holes:. Loop Formation

NASA Astrophysics Data System (ADS)

Dubath, Florian; Sakellariadou, Mairi; Viallet, Claude Michel

We study the deformation of a long cosmic string by a nearby rotating black hole. We examine whether the deformation of a cosmic string, induced by the gravitational field of a Kerr black hole, may lead to the formation of a string loop. The segment of the string which enters the ergo-sphere of a rotating black hole gets deformed and, if it is sufficiently twisted, it can self-intersect, chopping off a loop. We find that the formation of a loop, via such a mechanism, is a rare event. It will only arise in a small region of the collision phase space, which depends on the string velocity, the impact parameter and the black hole angular momentum. We conclude that, generically, a long cosmic string is simply scattered, or captured, by a nearby rotating black hole.

Superconducting cosmic string loops as sources for fast radio bursts

NASA Astrophysics Data System (ADS)

Cao, Xiao-Feng; Yu, Yun-Wei

2018-01-01

The cusp burst radiation of superconducting cosmic string (SCS) loops is thought to be a possible origin of observed fast radio bursts with the model-predicted radiation spectrum and the redshift- and energy-dependent event rate, we fit the observational redshift and energy distributions of 21 Parkes fast radio bursts and constrain the model parameters. It is found that the model can basically be consistent with the observations, if the current on the SCS loops has a present value of ˜1016μ179 /10 esu s-1 and evolves with redshift as an empirical power law ˜(1 +z )-1.3 , where μ17=μ /1017 g cm-1 is the string tension. This current evolution may provide a clue to probe the evolution of the cosmic magnetic fields and the gathering of the SCS loops to galaxy clusters.

The effects of spaceflight on open-loop and closed-loop postural control mechanisms: human neurovestibular studies on SLS-2

NASA Technical Reports Server (NTRS)

Collins, J. J.; De Luca, C. J.; Pavlik, A. E.; Roy, S. H.; Emley, M. S.; Young, L. R. (Principal Investigator)

1995-01-01

Stabilogram-diffusion analysis was used to examine how prolonged periods in microgravity affect the open-loop and closed-loop postural control mechanisms. It was hypothesized that following spaceflight: (1) the effective stochastic activity of the open-loop postural control schemes in astronauts is increased; (2) the effective stochastic activity and uncorrelated behavior, respectively, of the closed-loop postural control mechanisms in astronauts are increased; and (3) astronauts utilized open-loop postural controls schemes for shorter time intervals and smaller displacements. Four crew members and two alternates from the 14-day Spacelab Life Sciences 2 Mission were included in the study. Each subject was tested under eyes-open, quiet-standing conditions on multiple preflight and postflight days. The subjects' center-of-pressure trajectories were measured with a force platform and analyzed according to stabilogram-diffusion analysis. It was found that the effective stochastic activity of the open-loop postural control schemes in three of the four crew members was increased following spaceflight. This result is interpreted as an indication that there may be in-flight adaptations to higher-level descending postural control pathways, e.g., a postflight increase in the tonic activation of postural muscles. This change may also be the consequence of a compensatory (e.g., "stiffening") postural control strategy that is adopted by astronauts to account for general feeling of postflight unsteadiness. The crew members, as a group, did not exhibit any consistent preflight/postflight differences in the steady-state behavior of their closed-loop postural control mechanisms or in the functional interaction of their open-loop and closed-loop postural control mechanisms. These results are interpreted as indications that although there may be in-flight adaptations to the vestibular system and/or proprioceptive system, input from the visual system can compensate for such changes during undisturbed stance.

An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold

PubMed Central

Chiavegato, Angela; Zonta, Micaela; Cammarota, Mario; Brondi, Marco; Vetri, Francesco; Uva, Laura; Pozzan, Tullio; de Curtis, Marco; Ratto, Gian Michele; Carmignoto, Giorgio

2010-01-01

Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures. PMID:20405049

HRD Motif as the Central Hub of the Signaling Network for Activation Loop Autophosphorylation in Abl Kinase.

PubMed

La Sala, Giuseppina; Riccardi, Laura; Gaspari, Roberto; Cavalli, Andrea; Hantschel, Oliver; De Vivo, Marco

2016-11-08

A number of structural factors modulate the activity of Abelson (Abl) tyrosine kinase, whose deregulation is often related to oncogenic processes. First, only the open conformation of the Abl kinase domain's activation loop (A-loop) favors ATP binding to the catalytic cleft. In this regard, the trans-autophosphorylation of the Y412 residue, which is located along the A-loop, favors the stability of the open conformation, in turn enhancing Abl activity. Another key factor for full Abl activity is the formation of active conformations of the catalytic DFG motif in the Abl kinase domain. Furthermore, binding of the SH2 domain to the N-lobe of the Abl kinase was recently demonstrated to have a long-range allosteric effect on the stabilization of the A-loop open state. Intriguingly, these distinct structural factors imply a complex signal transmission network for controlling the A-loop's flexibility and conformational preference for optimal Abl function. However, the exact dynamical features of this signal transmission network structure remain unclear. Here, we report on microsecond-long molecular dynamics coupled with enhanced sampling simulations of multiple Abl model systems, in the presence or absence of the SH2 domain and with the DFG motif flipped in two ways (in or out conformation). Through comparative analysis, our simulations augment the interpretation of the existing Abl experimental data, revealing a dynamical network of interactions that interconnect SH2 domain binding with A-loop plasticity and Y412 autophosphorylation in Abl. This signaling network engages the DFG motif and, importantly, other conserved structural elements of the kinase domain, namely, the EPK-ELK H-bond network and the HRD motif. Our results show that the signal propagation for modulating the A-loop spatial localization is highly dependent on the HRD motif conformation, which thus acts as the central hub of this (allosteric) signaling network controlling Abl activation and function.

High-Performance Computing Data Center Waste Heat Reuse | Computational

Science.gov Websites

control room With heat exchangers, heat energy in the energy recovery water (ERW) loop becomes available to heat the facility's process hot water (PHW) loop. Once heated, the PHW loop supplies: Active loop in the courtyard of the ESIF's main entrance District heating loop: If additional heat is needed

Nicotiana alata Defensin Chimeras Reveal Differences in the Mechanism of Fungal and Tumor Cell Killing and an Enhanced Antifungal Variant

PubMed Central

Payne, Jennifer A. E.; Hayes, Brigitte M. E.; Durek, Thomas; Craik, David J.; Shafee, Thomas M. A.; Poon, Ivan K. H.; Hulett, Mark D.; van der Weerden, Nicole L.

2016-01-01

The plant defensin NaD1 is a potent antifungal molecule that also targets tumor cells with a high efficiency. We examined the features of NaD1 that contribute to these two activities by producing a series of chimeras with NaD2, a defensin that has relatively poor activity against fungi and no activity against tumor cells. All plant defensins have a common tertiary structure known as a cysteine-stabilized α-β motif which consists of an α helix and a triple-stranded β-sheet stabilized by four disulfide bonds. The chimeras were produced by replacing loops 1 to 7, the sequences between each of the conserved cysteine residues on NaD1, with the corresponding loops from NaD2. The loop 5 swap replaced the sequence motif (SKILRR) that mediates tight binding with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and is essential for the potent cytotoxic effect of NaD1 on tumor cells. Consistent with previous reports, there was a strong correlation between PI(4,5)P2 binding and the tumor cell killing activity of all of the chimeras. However, this correlation did not extend to antifungal activity. Some of the loop swap chimeras were efficient antifungal molecules, even though they bound poorly to PI(4,5)P2, suggesting that additional mechanisms operate against fungal cells. Unexpectedly, the loop 1B swap chimera was 10 times more active than NaD1 against filamentous fungi. This led to the conclusion that defensin loops have evolved as modular components that combine to make antifungal molecules with variable mechanisms of action and that artificial combinations of loops can increase antifungal activity compared to that of the natural variants. PMID:27503651

Activation of Latent Dihydroorotase from Aquifex aeolicus by Pressure*

PubMed Central

Hervé, Guy; Evans, Hedeel Guy; Fernado, Roshini; Patel, Chandni; Hachem, Fatme; Evans, David R.

2017-01-01

Elevated hydrostatic pressure was used to probe conformational changes of Aquifex aeolicus dihydroorotase (DHO), which catalyzes the third step in de novo pyrimidine biosynthesis. The isolated protein, a 45-kDa monomer, lacks catalytic activity but becomes active upon formation of a dodecameric complex with aspartate transcarbamoylase (ATC). X-ray crystallographic studies of the isolated DHO and of the complex showed that association induces several major conformational changes in the DHO structure. In the isolated DHO, a flexible loop occludes the active site blocking the access of substrates. The loop is mostly disordered but is tethered to the active site region by several electrostatic and hydrogen bonds. This loop becomes ordered and is displaced from the active site upon formation of DHO-ATC complex. The application of pressure to the complex causes its time-dependent dissociation and the loss of both DHO and ATC activities. Pressure induced irreversible dissociation of the obligate ATC trimer, and as a consequence the DHO is also inactivated. However, moderate hydrostatic pressure applied to the isolated DHO subunit mimics the complex formation and reversibly activates the isolated subunit in the absence of ATC, suggesting that the loop has been displaced from the active site. This effect of pressure is explained by the negative volume change associated with the disruption of ionic interactions and exposure of ionized amino acids to the solvent (electrostriction). The interpretation that the loop is relocated by pressure was validated by site-directed mutagenesis and by inhibition by small peptides that mimic the loop residues. PMID:27746403

Assessing catchment connectivity using hysteretic loops

NASA Astrophysics Data System (ADS)

Keesstra, Saskia; Masselink, Rens; Goni, Mikel; Campo, Miguel Angel; Gimenez, Rafael; Casali, Javier; Seeger, Manuel

2015-04-01

Sediment connectivity is a concept which can explain the origin, pathways and sinks of sediments within landscapes. This information is valuable for land managers to be able to take appropriate action at the correct place. Hysteresis between sediment and water discharge can give important information about the sources , pathways and conditions of sediment that arrives at the outlet of a catchment. "Hysteresis" happens when the sediment concentration associated with a certain flow rate is different depending on the direction in which the analysis is performed -towards the increase or towards the diminution of the flow. This phenomenon to some extent reflects the way in which the runoff generation processes are conjugated with those of the production and transport of sediments, hence the usefulness of hysteresis as a diagnostic hydrological parameter. However, the complexity of the phenomena and factors which determine hysteresis make its interpretation uncertain or, at the very least, problematic. Many types of hysteretic loops have been described as well as the cause for the shape of the loop, mainly describing the origin of the sediments. In this study, several measures to objectively classify hysteretic loops in an automated way were developed. These were consecutively used to classify several hundreds of loops from several agricultural catchments in Northern Spain. The data set for this study comes from four experimental watersheds in Navarre (Spain), owned and maintained by the Government of Navarre. These experimental watersheds have been monitored and studied since 1996 (La Tejería and Latxaga) and 2001 (Oskotz "principal", Op, and Oskotz "woodland", Ow). La Tejería and Latxaga watersheds, located in the Central Western part of Navarre, are roughly similar to each other regarding size (approximately 200 ha), geology (marls and sandstones), soils (fine texture topsoil), climate (humid sub Mediterranean) and land use (80-90% cultivated with winter grain crops). On the other hand, Op (ca.1,700 ha) is covered with forest and pasture (cattle-breeding); while Ow (ca. 500 ha), a sub-watershed of the Op, is almost completely covered with forest. The predominant climate in Op/Ow is sub-Atlantic. Furthermore, antecedent conditions and event characteristics were analysed. The loops were compared quantitatively and qualitatively between catchments for similar events and within the catchments for events with different characteristics.

Stretched Loops

NASA Image and Video Library

2017-03-16

When an active region rotated over to the edge of the sun, it presented us with a nice profile view of its elongated loops stretching and swaying above it (Mar. 8-9, 2017). These loops are actually charged particles (made visible in extreme ultraviolet light) swirling along the magnetic field lines of the active region. The video covers about 30 hours of activity. Also of note is a darker twisting mass of plasma to the left of the active region being pulled and spun about by magnetic forces. Video is available at http://photojournal.jpl.nasa.gov/catalog/PIA21562

A molecular mechanism of P-loop pliability of Rho-kinase investigated by molecular dynamic simulation

NASA Astrophysics Data System (ADS)

Gohda, Keigo; Hakoshima, Toshio

2008-11-01

Rho-kinase is a leading player in the regulation of cytoskeletal events involving smooth muscle contraction and neurite growth-cone collapse and retraction, and is a promising drug target in the treatment of both vascular and neurological disorders. Recent crystal structure of Rho-kinase complexed with a small-molecule inhibitor fasudil has revealed structural details of the ATP-binding site, which represents the target site for the inhibitor, and showed that the conserved phenylalanine on the P-loop occupies the pocket, resulting in an increase of protein-ligand contacts. Thus, the P-loop pliability is considered to play an important role in inhibitor binding affinity and specificity. In this study, we carried out a molecular dynamic simulation for Rho-kinase-fasudil complexes with two different P-loop conformations, i.e., the extended and folded conformations, in order to understand the P-loop pliability and dynamics at atomic level. A PKA-fasudil complex was also used for comparison. In the MD simulation, the flip-flop movement of the P-loop conformation starting either from the extended or folded conformation was not able to be observed. However, a significant conformational change in a long loop region covering over the P-loop, and also alteration of ionic interaction-manner of fasudil with acidic residues in the ATP binding site were shown only in the Rho-kinase-fasudil complex with the extended P-loop conformation, while Rho-kinase with the folded P-loop conformation and PKA complexes did not show large fluctuations, suggesting that the Rho-kinase-fasudil complex with the extended P-loop conformation represents a meta-stable state. The information of the P-loop pliability at atomic level obtained in this study could provide valuable clues to designing potent and/or selective inhibitors for Rho-kinase.

Impact of Active Control on Passive Safety Response Characteristics of Sodium-cooled Fast Reactors: I - Theoretical background

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

Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.

Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less

Impact of Active Control on Passive Safety Response Characteristics of Sodium-cooled Fast Reactors: I - Theoretical background

DOE PAGES

Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.

2017-06-21

Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less

Quasi-periodic Counter-propagating Fast Magnetosonic Wave Trains from Neighboring Flares: SDO/AIA Observations and 3D MHD Modeling

NASA Astrophysics Data System (ADS)

Ofman, Leon; Liu, Wei

2018-06-01

Since their discovery by the Solar Dynamics Observatory/Atmospheric Imaging Assembly (AIA) in the extreme ultraviolet, rapid (phase speeds of ∼1000 km s‑1), quasi-periodic, fast-mode propagating (QFP) wave trains have been observed accompanying many solar flares. They typically propagate in funnel-like structures associated with the expanding magnetic field topology of the active regions (ARs). The waves provide information on the associated flare pulsations and the magnetic structure through coronal seismology (CS). The reported waves usually originate from a single localized source associated with the flare. Here we report the first detection of counter-propagating QFPs associated with two neighboring flares on 2013 May 22, apparently connected by large-scale, trans-equatorial coronal loops. We present the first results of a 3D MHD model of counter-propagating QFPs in an idealized bipolar AR. We investigate the excitation, propagation, nonlinearity, and interaction of the counter-propagating waves for a range of key model parameters, such as the properties of the sources and the background magnetic structure. In addition to QFPs, we also find evidence of trapped fast- (kink) and slow-mode waves associated with the event. We apply CS to determine the magnetic field strength in an oscillating loop during the event. Our model results are in qualitative agreement with the AIA-observed counter-propagating waves and used to identify the various MHD wave modes associated with the observed event, providing insights into their linear and nonlinear interactions. Our observations provide the first direct evidence of counter-propagating fast magnetosonic waves that can potentially lead to turbulent cascade and carry significant energy flux for coronal heating in low-corona magnetic structures.

Automatic Earthquake Detection by Active Learning

NASA Astrophysics Data System (ADS)

Bergen, K.; Beroza, G. C.

2017-12-01

In recent years, advances in machine learning have transformed fields such as image recognition, natural language processing and recommender systems. Many of these performance gains have relied on the availability of large, labeled data sets to train high-accuracy models; labeled data sets are those for which each sample includes a target class label, such as waveforms tagged as either earthquakes or noise. Earthquake seismologists are increasingly leveraging machine learning and data mining techniques to detect and analyze weak earthquake signals in large seismic data sets. One of the challenges in applying machine learning to seismic data sets is the limited labeled data problem; learning algorithms need to be given examples of earthquake waveforms, but the number of known events, taken from earthquake catalogs, may be insufficient to build an accurate detector. Furthermore, earthquake catalogs are known to be incomplete, resulting in training data that may be biased towards larger events and contain inaccurate labels. This challenge is compounded by the class imbalance problem; the events of interest, earthquakes, are infrequent relative to noise in continuous data sets, and many learning algorithms perform poorly on rare classes. In this work, we investigate the use of active learning for automatic earthquake detection. Active learning is a type of semi-supervised machine learning that uses a human-in-the-loop approach to strategically supplement a small initial training set. The learning algorithm incorporates domain expertise through interaction between a human expert and the algorithm, with the algorithm actively posing queries to the user to improve detection performance. We demonstrate the potential of active machine learning to improve earthquake detection performance with limited available training data.

Post-flare loops embedded in a hot coronal fan-like structure

NASA Technical Reports Server (NTRS)

Svestka, Z.; Farnik, F.; Hudson, H. S.; Hick, P.

1997-01-01

Limb events were demonstrated on the sun in which rising post-flare loops were embedded in hot structures looking in soft X-rays like fans of rays, formed during the flare and extending high into the corona. One of these structures is analyzed and it is suggested that these fans of rays represent temporary ministreamers, along which mass flows into interplanetary space. This suggestion is supported by maps of solar wind density constructed from scintillation measurements.

Decay-less kink oscillations in coronal loops

NASA Astrophysics Data System (ADS)

Anfinogentov, S.; Nisticò, G.; Nakariakov, V. M.

2013-12-01

Context. Kink oscillations of coronal loops in an off-limb active region are detected with the Imaging Assembly Array (AIA) instruments of the Solar Dynamics Observatory (SDO) at 171 Å. Aims: We aim to measure periods and amplitudes of kink oscillations of different loops and to determinate the evolution of the oscillation phase along the oscillating loop. Methods: Oscillating coronal loops were visually identified in the field of view of SDO/AIA and STEREO/EUVI-A: the loop length was derived by three-dimensional analysis. Several slits were taken along the loops to assemble time-distance maps. We identified oscillatory patterns and retrieved periods and amplitudes of the oscillations. We applied the cross-correlation technique to estimate the phase shift between oscillations at different segments of oscillating loops. Results: We found that all analysed loops show low-amplitude undamped transverse oscillations. Oscillation periods of loops in the same active region range from 2.5 to 11 min, and are different for different loops. The displacement amplitude is lower than 1 Mm. The oscillation phase is constant along each analysed loop. The spatial structure of the phase of the oscillations corresponds to the fundamental standing kink mode. We conclude that the observed behaviour is consistent with the empirical model in terms of a damped harmonic resonator affected by a non-resonant continuously operating external force. A movie is available in electronic form at http://www.aanda.org

Coronal Structure of a Flaring Region and Associated Coronal Mass Ejection

NASA Technical Reports Server (NTRS)

Kundu, Mukul R.; Manoharan, P. K.

2003-01-01

We report the multiwavelength investigations of an eruptive flare event that occurred on 2001 April 2 at about 11 UT. The manifestations associated with this flare event have been studied from the near-Sun region to about 0.5 AU. The H-alpha images from the Meudon Spectroheliograph reveal a fast spectacular eruption of plasmoids from the flare site to the west and a Moreton wave disturbance propagating toward the south, A bright, fast, wide coronal mass ejection (CME) associated with this eruptive event was imaged by SOHO/LASCO and the remote-sensing interplanetary scintillation technique. The timings and positions of the Type II radio bursts, H-alpha eruption, and CME onset as well as the magnetic field configuration suggest a release of energy at the null point. The results seem to support the "breakout" scenario proposed by Antiochos and coworkers, and they are also suggestive that the energy release is followed by magnetic reconnection between the low-lying loops near the separatrix and the loop system above them.

Detection of siRNA Mediated Target mRNA Cleavage Activities in Human Cells by a Novel Stem-Loop Array RT-PCR Analysis

DTIC Science & Technology

2016-09-07

sequences of the target mRNA, and a double stranded stem at the 5′ end that forms a stem -loop to function as a forceps to stabilize the secondary...E-mjournal homepage: www.elsevier.com/locate/bbrepDetection of siRNA-mediated target mRNA cleavage activities in human cells by a novel stem -loop...challenges for the accurate and efficient detection and verification of cleavage sites on target mRNAs. Here we used a sensitive stem -loop array reverse

Sweeping Arches and Loops [video

NASA Image and Video Library

2014-07-10

Two active regions with their intense magnetic fields produced towering arches and spiraling coils of solar loops above them (June 29 - July 1, 2014) as they rotated into view. When viewed in extreme ultraviolet light, magnetic field lines are revealed by charged particles that travel along them. These active regions appear as dark sunspots when viewed in filtered light. Note the small blast in the upper of the two major active regions, followed by more coils of loops as the region reorganizes itself. The still was taken on June 30 at 10:33 UT. Credit: NASA/Solar Dynamics Observatory Two active regions with their intense magnetic fields produced towering arches and spiraling coils of solar loops above them (June 29 - July 1, 2014) as they rotated into view. When viewed in extreme ultraviolet light, magnetic field lines are revealed by charged particles that travel along them. These active regions appear as dark sunspots when viewed in filtered light. Note the small blast in the upper of the two major active regions, followed by more coils of loops as the region reorganizes itself. The still was taken on June 30 at 10:33 UT. Credit: Solar Dynamics Observatory/NASA.

MHD simulation of the Bastille day event

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

Linker, Jon, E-mail: linkerj@predsci.com; Torok, Tibor; Downs, Cooper

2016-03-25

We describe a time-dependent, thermodynamic, three-dimensional MHD simulation of the July 14, 2000 coronal mass ejection (CME) and flare. The simulation starts with a background corona developed using an MDI-derived magnetic map for the boundary condition. Flux ropes using the modified Titov-Demoulin (TDm) model are used to energize the pre-event active region, which is then destabilized by photospheric flows that cancel flux near the polarity inversion line. More than 10{sup 33} ergs are impulsively released in the simulated eruption, driving a CME at 1500 km/s, close to the observed speed of 1700km/s. The post-flare emission in the simulation is morphologically similarmore » to the observed post-flare loops. The resulting flux rope that propagates to 1 AU is similar in character to the flux rope observed at 1 AU, but the simulated ICME center passes 15° north of Earth.« less

Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons

PubMed Central

Müller, Jan; Bakkum, Douglas J.; Hierlemann, Andreas

2012-01-01

We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

Theory on the mechanism of distal action of transcription factors: looping of DNA versus tracking along DNA

NASA Astrophysics Data System (ADS)

Murugan, R.

2010-10-01

In this paper, we develop a theory on the mechanism of distal action of the transcription factors, which are bound at their respective cis-regulatory enhancer modules on the promoter-RNA polymerase II (PR) complexes to initiate the transcription event in eukaryotes. We consider both the looping and tracking modes of their distal communication and calculate the mean first passage time that is required for the distal interactions of the complex of enhancer and transcription factor with the PR via both these modes. We further investigate how this mean first passage time is dependent on the length of the DNA segment (L, base-pairs) that connects the cis-regulatory binding site and the respective promoter. When the radius of curvature of this connecting segment of DNA is R that was induced upon binding of the transcription factor at the cis-acting element and RNAPII at the promoter in cis-positions, our calculations indicate that the looping mode of distal action will dominate when L is such that L > 2πR and the tracking mode of distal action will be favored when L < 2πR. The time required for the distal action will be minimum when L = 2πR where the typical value of R for the binding of histones will be R ~ 16 bps and L ~ 102 bps. It seems that the free energy associated with the binding of the transcription factor with its cis-acting element and the distance of this cis-acting element from the corresponding promoter of the gene of interest is negatively correlated. Our results suggest that the looping and tracking modes of distal action are concurrently operating on the transcription activation and the physics that determines the timescales associated with the looping/tracking in the mechanism of action of these transcription factors on the initiation of the transcription event must put a selection pressure on the distribution of the distances of cis-regulatory modules from their respective promoters of the genes. The computational analysis of the upstream sequences of promoters of various genes in the human and mouse genomes for the presence of putative cis-regulatory elements for a set of known transcription factors using the position weight matrices available with the JASPAR database indicates the presence of cis-acting elements with maximum probability at a distance of ~102 bps from the promoters which substantiates our theoretical predictions.

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

Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.

Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less

DETECTING NANOFLARE HEATING EVENTS IN SUBARCSECOND INTER-MOSS LOOPS USING Hi-C

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

Winebarger, Amy R.; Moore, Ronald; Cirtain, Jonathan

2013-07-01

The High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket on 2012 July 11 and captured roughly 345 s of high-spatial and temporal resolution images of the solar corona in a narrowband 193 A channel. In this paper, we analyze a set of rapidly evolving loops that appear in an inter-moss region. We select six loops that both appear in and fade out of the Hi-C images during the short flight. From the Hi-C data, we determine the size and lifetimes of the loops and characterize whether these loops appear simultaneously along their length or first appear at onemore » footpoint before appearing at the other. Using co-aligned, co-temporal data from multiple channels of the Atmospheric Imaging Assembly on the Solar Dynamics Observatory, we determine the temperature and density of the loops. We find the loops consist of cool ({approx}10{sup 5} K), dense ({approx}10{sup 10} cm{sup -3}) plasma. Their required thermal energy and their observed evolution suggest they result from impulsive heating similar in magnitude to nanoflares. Comparisons with advanced numerical simulations indicate that such dense, cold and short-lived loops are a natural consequence of impulsive magnetic energy release by reconnection of braided magnetic field at low heights in the solar atmosphere.« less

Use of an open-loop system to increase physical activity

USDA-ARS?s Scientific Manuscript database

This study evaluated the effectiveness of an open-loop system that reinforces physical activity with TV watching to increase children’s physical activity. Non-overweight, sedentary boys and girls (8-12 y) were randomized to a group that received feedback of activity counts + reinforcement for physic...

Fetal demise by umbilical cord around abdomen and stricture.

PubMed

Tan, Shun-Jen; Chen, Chi-Huang; Wu, Gwo-Jang; Chen, Wei-Hwa; Chang, Cheng-Chang

2010-01-01

Umbilical cord abnormalities are accepted as conditions associated with intrauterine fetal demise (IUFD), and umbilical cord stricture is most frequently encountered. In addition, although cord entanglement with multiple loops rarely increases the perinatal mortality, it is associated with a significant increase in variable kind of morbidity such as growth restriction. We describe a 27-year-old woman, with a missed abortion history at about 10 weeks' gestation in her first pregnancy, who presented to our outpatient department at 34 4/7 weeks of gestation due to decreased fetal activity during the preceding week. No fetal heart activity and blood flow had been detected by ultrasonography and pulsed-wave Doppler. A demised fetus with umbilical cord stricture and three loops around abdomen was delivered and was weighted 1,830 g that was below the tenth percentile for the gestational age. Either umbilical cord stricture or entanglement around the body can affect the development of the fetus and even be lethal. The former might play a more important role in this case. Their etiology and the sequence of the events are still undetermined, and additional evaluation such as autopsy and further research may be needed. In addition, counsel and frequent fetal surveillance should be done in patients with previous IUFD attributed to cord stricture during next pregnancy because of undetermined risk of recurrence.

cPLA2α Gene Activation by IL-1β is Dependent on an Upstream Kinase pathway, Enzymatic Activation and Downstream 15-lipoxygenase Activity: A Positive Feedback Loop

PubMed Central

Walters, Jewell N.; Bickford, Justin S.; Beachy, Dawn E.; Newsom, Kimberly J.; Herlihy, John-David H.; Peck, Molly V.; Qiu, Xiaolei; Nick, Harry S.

2011-01-01

Cytosolic phospholipase A2α (cPLA2α) is the most widely studied member of the Group IV PLA2 family. The enzyme is Ca2+-dependent with specificity for phospholipid substrates containing arachidonic acid. As the pinnacle of the arachidonic acid pathway, cPLA2α has a primary role in the biosynthesis of a diverse family of eicosanoid metabolites, with potent physiological, inflammatory and pathological consequences. cPLA2α activity is regulated by pro-inflammatory stimuli through pathways involving increased intracellular Ca2+ levels, phosphorylation coupled to increased enzymatic activity and de novo gene transcription. This study addresses the signal transduction pathways for protein phosphorylation and gene induction following IL-1β stimulation in human fetal lung fibroblasts. Our results utilizing both inhibitors and kinase-deficient cells demonstrate that cPLA2α is phosphorylated within 10 min of IL-1β treatment, an event requiring p38 MAPK as well as the upstream kinase, MKK3/MKK6. Inhibition of p38 MAPK also blocks the phosphorylation of a downstream, nuclear kinase, MSK-1. Our results further demonstrate that the activities of both cPLA2α and a downstream lipoxygenase (15-LOX2) are required for IL-1β-dependent induction of cPLA2α mRNA expression. Overall, these data support an MKK3/MKK6→p38 MAPK→MSK-1→cPLA2α→15-LOX2-dependent, positive feedback loop where a protein’s enzymatic activity is required to regulate its own gene induction by a pro-inflammatory stimulus. PMID:21771656

Real-time monitoring of CO2 storage sites: Application to Illinois Basin-Decatur Project

USGS Publications Warehouse

Picard, G.; Berard, T.; Chabora, E.; Marsteller, S.; Greenberg, S.; Finley, R.J.; Rinck, U.; Greenaway, R.; Champagnon, C.; Davard, J.

2011-01-01

Optimization of carbon dioxide (CO2) storage operations for efficiency and safety requires use of monitoring techniques and implementation of control protocols. The monitoring techniques consist of permanent sensors and tools deployed for measurement campaigns. Large amounts of data are thus generated. These data must be managed and integrated for interpretation at different time scales. A fast interpretation loop involves combining continuous measurements from permanent sensors as they are collected to enable a rapid response to detected events; a slower loop requires combining large datasets gathered over longer operational periods from all techniques. The purpose of this paper is twofold. First, it presents an analysis of the monitoring objectives to be performed in the slow and fast interpretation loops. Second, it describes the implementation of the fast interpretation loop with a real-time monitoring system at the Illinois Basin-Decatur Project (IBDP) in Illinois, USA. ?? 2011 Published by Elsevier Ltd.

A ``perfect'' Late Phase Flare Loop: X-ray And Radio Studies

NASA Astrophysics Data System (ADS)

Bain, Hazel; Fletcher, L.

2009-05-01

We present observations of a GOES X3.1 class flare which occurred on the 24th August 2002. The event was observed by a number of instruments including RHESSI, TRACE and NoRH. This flare is particularly interesting due to its position and orientation on the west limb of the Sun. The flare appears to be perpendicular to the line of sight making it possible to ascertain the geometrical parameters of the post flare arcade loops. We investigate the decay phase of the flare by comparing X-ray and radio observations of the post flare arcade loops with models of soft x-ray and thermal gyrosynchrotron emission to characterise the electron distribution present within the loop. HMB gratefully acknowledges the support of an SPD and STFC studentship. LF gratefully acknowledges the support of an STFC Rolling Grant, and financial support by the European Commission through the SOLAIRE Network (MTRN-CT_2006-035484)

Nanoflares, Spicules, and Other Small-Scale Dynamic Phenomena on the Sun

NASA Technical Reports Server (NTRS)

Klimchuk, James

2010-01-01

There is abundant evidence of highly dynamic phenomena occurring on very small scales in the solar atmosphere. For example, the observed pr operties of many coronal loops can only be explained if the loops are bundles of unresolved strands that are heated impulsively by nanoflares. Type II spicules recently discovered by Hinode are an example of small-scale impulsive events occurring in the chromosphere. The exist ence of these and other small-scale phenomena is not surprising given the highly structured nature of the magnetic field that is revealed by photospheric observations. Dynamic phenomena also occur on much lar ger scales, including coronal jets, flares, and CMEs. It is tempting to suggest that these different phenomena are all closely related and represent a continuous distribution of sizes and energies. However, this is a dangerous over simplification in my opinion. While it is tru e that the phenomena all involve "magnetic reconnection" (the changin g of field line connectivity) in some form, how this occurs depends s trongly on the magnetic geometry. A nanoflare resulting from the interaction of tangled magnetic strands within a confined coronal loop is much different from a major flare occurring at the current sheet form ed when a CME rips open an active region. I will review the evidence for ubiquitous small-scale dynamic phenomena on the Sun and discuss wh y different phenomena are not all fundamentally the same.

Understanding Which Residues of the Active Site and Loop Structure of a Tyrosine Aminomutase Define Its Mutase and Lyase Activities.

PubMed

Attanayake, Gayanthi; Walter, Tyler; Walker, Kevin D

2018-05-30

Site-directed mutations and substrate analogues were used to gain insights into the branch-point reaction of the 3,5-dihydro-5-methylidene-4 H-imidazol-4-one (MIO)-tyrosine aminomutase from Oryza sativa ( OsTAM). Exchanging the active residues of OsTAM (Y125C/N446K) for those in a phenylalanine aminomutase TcPAM altered its substrate specificity from tyrosine to phenylalanine. The aminomutase mechanism of OsTAM surprisingly changed almost exclusively to that of an ammonia lyase making cinnamic acid (>95%) over β-phenylalanine [Walter, T., et al. (2016) Biochemistry 55, 3497-3503]. We hypothesized that the missing electronics or sterics on the aryl ring of the phenylalanine substrate, compared with the sizable electron-donating hydroxyl of the natural tyrosine substrate, influenced the unexpected lyase reactivity of the OsTAM mutant. The double mutant was incubated with 16 α-phenylalanine substituent analogues of varying electronic strengths and sterics. The mutant converted each analogue principally to its acrylate with ∼50% conversion of the p-Br substrate, making only a small amount of the β-amino acid. The inner loop structure over the entrance to the active site was also mutated to assess how the lyase and mutase activities are affected. An OsTAM loop mutant, matching the loop residues of TcPAM, still chiefly made >95% of the acrylate from each substrate. A combined active site:loop mutant was most reactive but remained a lyase, making 10-fold more acrylates than other mutants did. While mutations within the active site changed the substrate specificity of OsTAM, continued exploration is needed to fully understand the interplay among the inner loop, the substrate, and the active site in defining the mutase and lyase activities.

Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase

PubMed Central

2012-01-01

Background During elongation, multi-subunit RNA polymerases (RNAPs) cycle between phosphodiester bond formation and nucleic acid translocation. In the conformation associated with catalysis, the mobile “trigger loop” of the catalytic subunit closes on the nucleoside triphosphate (NTP) substrate. Closing of the trigger loop is expected to exclude water from the active site, and dehydration may contribute to catalysis and fidelity. In the absence of a NTP substrate in the active site, the trigger loop opens, which may enable translocation. Another notable structural element of the RNAP catalytic center is the “bridge helix” that separates the active site from downstream DNA. The bridge helix may participate in translocation by bending against the RNA/DNA hybrid to induce RNAP forward movement and to vacate the active site for the next NTP loading. The transition between catalytic and translocation conformations of RNAP is not evident from static crystallographic snapshots in which macromolecular motions may be restrained by crystal packing. Results All atom molecular dynamics simulations of Thermus thermophilus (Tt) RNAP reveal flexible hinges, located within the two helices at the base of the trigger loop, and two glycine hinges clustered near the N-terminal end of the bridge helix. As simulation progresses, these hinges adopt distinct conformations in the closed and open trigger loop structures. A number of residues (described as “switch” residues) trade atomic contacts (ion pairs or hydrogen bonds) in response to changes in hinge orientation. In vivo phenotypes and in vitro activities rendered by mutations in the hinge and switch residues in Saccharomyces cerevisiae (Sc) RNAP II support the importance of conformational changes predicted from simulations in catalysis and translocation. During simulation, the elongation complex with an open trigger loop spontaneously translocates forward relative to the elongation complex with a closed trigger loop. Conclusions Switching between catalytic and translocating RNAP forms involves closing and opening of the trigger loop and long-range conformational changes in the atomic contacts of amino acid side chains, some located at a considerable distance from the trigger loop and active site. Trigger loop closing appears to support chemistry and the fidelity of RNA synthesis. Trigger loop opening and limited bridge helix bending appears to promote forward nucleic acid translocation. PMID:22676913

Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

PubMed

Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G

2018-02-01

R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiple Flow Loop SCADA System Implemented on the Production Prototype Loop

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

Baily, Scott A.; Dalmas, Dale Allen; Wheat, Robert Mitchell

2015-11-16

The following report covers FY 15 activities to develop supervisory control and data acquisition (SCADA) system for the Northstar Moly99 production prototype gas flow loop. The goal of this effort is to expand the existing system to include a second flow loop with a larger production-sized blower. Besides testing the larger blower, this system will demonstrate the scalability of our solution to multiple flow loops.

MINI-FILAMENT ERUPTION AS THE INITIATION OF A JET ALONG CORONAL LOOPS

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

Hong, Junchao; Jiang, Yunchun; Yang, Jiayan

Minifilament eruptions (MFEs) and coronal jets are different types of solar small-scale explosive events. We report an MFE observed at the New Vacuum Solar Telescope (NVST). As seen in the NVST H α images, during the rising phase, the minifilament erupts outward orthogonally to its length, accompanied with a flare-like brightening at the bottom. Afterward, dark materials are found to possibly extend along the axis of the expanded filament body. The MFE is analogous to large filament eruptions. However, a simultaneous observation of the Solar Dynamics Observatory shows that a jet is initiated and flows out along nearby coronal loopsmore » during the rising phase of the MFE. Meanwhile, small hot loops, which connect the original eruptive site of the minifilament to the footpoints of the coronal loops, are formed successively. A differential emission measure analysis demonstrates that, on the top of the new small loops, a hot cusp structure exists. We conjecture that the magnetic fields of the MFE interact with magnetic fields of the coronal loops. This interaction is interpreted as magnetic reconnection that produces the jet and the small hot loops.« less

Loop propensity of the sequence YKGQP from staphylococcal nuclease: implications for the folding of nuclease.

PubMed

Patel, Sunita; Sasidhar, Yellamraju U

2007-10-01

Recently we performed molecular dynamics (MD) simulations on the folding of the hairpin peptide DTVKLMYKGQPMTFR from staphylococcal nuclease in explicit water. We found that the peptide folds into a hairpin conformation with native and nonnative hydrogen-bonding patterns. In all the folding events observed in the folding of the hairpin peptide, loop formation involving the region YKGQP was an important event. In order to trace the origins of the loop propensity of the sequence YKGQP, we performed MD simulations on the sequence starting from extended, polyproline II and native type I' turn conformations for a total simulation length of 300 ns, using the GROMOS96 force field under constant volume and temperature (NVT) conditions. The free-energy landscape of the peptide YKGQP shows minima corresponding to loop conformation with Tyr and Pro side-chain association, turn and extended conformational forms, with modest free-energy barriers separating the minima. To elucidate the role of Gly in facilitating loop formation, we also performed MD simulations of the mutated peptide YKAQP (Gly --> Ala mutation) under similar conditions starting from polyproline II conformation for 100 ns. Two minima corresponding to bend/turn and extended conformations were observed in the free-energy landscape for the peptide YKAQP. The free-energy barrier between the minima in the free-energy landscape of the peptide YKAQP was also modest. Loop conformation is largely sampled by the YKGQP peptide, while extended conformation is largely sampled by the YKAQP peptide. We also explain why the YKGQP sequence samples type II turn conformation in these simulations, whereas the sequence as part of the hairpin peptide DTVKLMYKGQPMTFR samples type I' turn conformation both in the X-ray crystal structure and in our earlier simulations on the folding of the hairpin peptide. We discuss the implications of our results to the folding of the staphylococcal nuclease. Copyright (c) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Conformation-selective inhibitors reveal differences in the activation and phosphate-binding loops of the tyrosine kinases Abl and Src

PubMed Central

Hari, Sanjay B.; Perera, B. Gayani K.; Ranjitkar, Pratistha; Seeliger, Markus A.; Maly, Dustin J.

2013-01-01

Over the last decade, an increasingly diverse array of potent and selective inhibitors that target the ATP-binding sites of protein kinases have been developed. Many of these inhibitors, like the clinically approved drug imatinib (Gleevec), stabilize a specific catalytically inactive ATP-binding site conformation of their kinases targets. Imatinib is notable in that it is highly selective for its kinase target, Abl, over other closely-related tyrosine kinases, like Src. In addition, imatinib is highly sensitive to the phosphorylation state of Abl's activation loop, which is believed to be a general characteristic of all inhibitors that stabilize a similar inactive ATP-binding site conformation. In this report, we perform a systematic analysis of a diverse series of ATP-competitive inhibitors that stabilize a similar inactive ATP-binding site conformation as imatinib with the tyrosine kinases Src and Abl. In contrast to imatinib, many of these inhibitors have very similar potencies against Src and Abl. Furthermore, only a subset of this class of inhibitors is sensitive to the phosphorylation state of the activation loop of these kinases. In attempting to explain this observation, we have uncovered an unexpected correlation between Abl's activation loop and another flexible active site feature, called the phosphate-binding loop (p-loop). These studies shed light on how imatinib is able to obtain its high target selectivity and reveal how the conformational preference of flexible active site regions can vary between closely related kinases. PMID:24106839

High Contrast X-ray Flares In The Anchors Database

NASA Astrophysics Data System (ADS)

McCleary, Jacqueline; Wolk, S.

2010-01-01

The X-ray light curves of pre-main sequence stars can show variability in the form of flares altering a baseline characteristic activity level; the largest X-ray flares are characterized by a rapid rise to 10 or more times the characteristic count rate, followed by a slower quasi-exponential decay. Analysis of these high-contrast X-ray flares enables the study of the innermost magnetic fields of pre-main sequence stars. We have scanned the ANCHORS database of Chandra observations of star-forming regions to extend the study of flare events on pre-main sequence stars both in sky coverage and in volume. We developed a sample of 30 high-contrast flares out of the 14,000 stars available in ANCHORS at the time of our study. By not biasing our sample by cluster, age, or spectral type, we increased the number of X-ray flare events studied and subsequently the strength of any statements about their properties. Applying the generally accepted methods of time-resolved spectral analysis developed by Reale et al. (1997), we measured the temperatures, confining magnetic field strengths, and loop lengths of these large flares. The results of the flare analysis were compared to the 2MASS and Spitzer data available for the stars in our sample. We found that the longest flare loop lengths (of order several stellar radii) are only seen on stars whose IR data indicates the presence of disks, which suggests that the longest flares may stretch all the way to the disk. Such long flares tend to be more tenuous (rarified) than the other large flares studied. A wide range of loop lengths were observed, indicating that two types of flares may occur on disked young stellar objects: either compact and analogous to flares on evolved stars, or long and the result of star-disk magnetic connections.

Brightness and magnetic evolution of solar coronal bright points

NASA Astrophysics Data System (ADS)

Ugarte Urra, Ignacio

This thesis presents a study of the brightness and magnetic evolution of several Extreme ultraviolet (EUV) coronal bright points (hereafter BPs). The study was carried out using several instruments on board the Solar and Heliospheric Observatory, supported by the high resolution imaging from the Transition Region And Coronal Explorer. The results confirm that, down to 1" resolution, BPs are made of small loops with lengths of [approximate]6 Mm and cross-sections of ≈2 Mm. The loops are very dynamic, evolving in time scales as short as 1 - 2 minutes. This is reflected in a highly variable EUV response with fluctuations highly correlated in spectral lines at transition region temperatures, but not always at coronal temperatures. A wavelet analysis of the intensity variations reveals the existence of quasi-periodic oscillations with periods ranging 400--1000s, in the range of periods characteristic of the chromospheric network. The link between BPs and network bright points is discussed, as well as the interpretation of the oscillations in terms of global acoustic modes of closed magnetic structures. A comparison of the magnetic flux evolution of the magnetic polarities to the EUV flux changes is also presented. Throughout their lifetime, the intrinsic EUV emission of BPs is found to be dependent on the total magnetic flux of the polarities. In short time scales, co-spatial and co-temporal coronal images and magnetograms, reveal the signature of heating events that produce sudden EUV brightenings simultaneous to magnetic flux cancellations. This is interpreted in terms of magnetic reconnection events. Finally, a electron density study of six coronal bright points produces values of ≈1.6×10 9 cm -3 , closer to active region plasma than to quiet Sun. The analysis of a large coronal loop (half length of 72 Mm) introduces the discussion on the prospects of future plasma diagnostics of BPs with forthcoming solar missions.

Enzymatic function of loop movement in enolase: preparation and some properties of H159N, H159A, H159F, and N207A enolases.

PubMed

Brewer, John M; Glover, Claiborne V C; Holland, Michael J; Lebioda, Lukasz

2003-05-01

The hypothesis that His159 in yeast enolase moves on a polypeptide loop to protonate the phosphoryl of 2-phosphoglycerate to initiate its conversion to phosphoenolpyruvate was tested by preparing H159N, H159A, and H159F enolases. These have 0.07%-0.25% of the native activity under standard assay conditions and the pH dependence of maximum velocities of H159A and H159N mutants is markedly altered. Activation by Mg2+ is biphasic, with the smaller Mg2+ activation constant closer to that of the "catalytic" Mg2+ binding site of native enolase and the larger in the mM range in which native enolase is inhibited. A third Mg2+ may bind to the phosphoryl, functionally replacing proton donation by His159. N207A enolase lacks an intersubunit interaction that stabilizes the closed loop(s) conformation when 2-phosphoglycerate binds. It has 21% of the native activity, also exhibits biphasic Mg2+ activation, and its reaction with the aldehyde analogue of the substrate is more strongly inhibited than is its normal enzymatic reaction. Polypeptide loop(s) closure may keep a proton from His159 interacting with the substrate phosphoryl oxygen long enough to stabilize a carbanion intermediate.

Evidence of Significant Energy Input in the Late Phase of a Solar Flare from NuSTAR X-Ray Observations

NASA Astrophysics Data System (ADS)

Kuhar, Matej; Krucker, Säm; Hannah, Iain G.; Glesener, Lindsay; Saint-Hilaire, Pascal; Grefenstette, Brian W.; Hudson, Hugh S.; White, Stephen M.; Smith, David M.; Marsh, Andrew J.; Wright, Paul J.; Boggs, Steven E.; Christensen, Finn E.; Craig, William W.; Hailey, Charles J.; Harrison, Fiona A.; Stern, Daniel; Zhang, William W.

2017-01-01

We present observations of the occulted active region AR 12222 during the third Nuclear Spectroscopic Telescope ARray (NuSTAR) solar campaign on 2014 December 11, with concurrent Solar Dynamics Observatory (SDO)/AIA and FOXSI-2 sounding rocket observations. The active region produced a medium-size solar flare 1 day before the observations, at ˜18 UT on 2014 December 10, with the post-flare loops still visible at the time of NuSTAR observations. The time evolution of the source emission in the SDO/AIA 335 Å channel reveals the characteristics of an extreme-ultraviolet late-phase event, caused by the continuous formation of new post-flare loops that arch higher and higher in the solar corona. The spectral fitting of NuSTAR observations yields an isothermal source, with temperature 3.8-4.6 MK, emission measure (0.3-1.8) × 1046 cm-3, and density estimated at (2.5-6.0) × 108 cm-3. The observed AIA fluxes are consistent with the derived NuSTAR temperature range, favoring temperature values in the range of 4.0-4.3 MK. By examining the post-flare loops’ cooling times and energy content, we estimate that at least 12 sets of post-flare loops were formed and subsequently cooled between the onset of the flare and NuSTAR observations, with their total thermal energy content an order of magnitude larger than the energy content at flare peak time. This indicates that the standard approach of using only the flare peak time to derive the total thermal energy content of a flare can lead to a large underestimation of its value.

EVIDENCE OF SIGNIFICANT ENERGY INPUT IN THE LATE PHASE OF A SOLAR FLARE FROM NuSTAR X-RAY OBSERVATIONS

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

Kuhar, Matej; Krucker, Säm; Hannah, Iain G.

We present observations of the occulted active region AR 12222 during the third Nuclear Spectroscopic Telescope ARray ( NuSTAR ) solar campaign on 2014 December 11, with concurrent Solar Dynamics Observatory ( SDO )/AIA and FOXSI-2 sounding rocket observations. The active region produced a medium-size solar flare 1 day before the observations, at ∼18 UT on 2014 December 10, with the post-flare loops still visible at the time of NuSTAR observations. The time evolution of the source emission in the SDO/ AIA 335 Å channel reveals the characteristics of an extreme-ultraviolet late-phase event, caused by the continuous formation of newmore » post-flare loops that arch higher and higher in the solar corona. The spectral fitting of NuSTAR observations yields an isothermal source, with temperature 3.8–4.6 MK, emission measure (0.3–1.8) × 10{sup 46} cm{sup −3}, and density estimated at (2.5–6.0) × 10{sup 8} cm{sup −3}. The observed AIA fluxes are consistent with the derived NuSTAR temperature range, favoring temperature values in the range of 4.0–4.3 MK. By examining the post-flare loops’ cooling times and energy content, we estimate that at least 12 sets of post-flare loops were formed and subsequently cooled between the onset of the flare and NuSTAR observations, with their total thermal energy content an order of magnitude larger than the energy content at flare peak time. This indicates that the standard approach of using only the flare peak time to derive the total thermal energy content of a flare can lead to a large underestimation of its value.« less

A competent catalytic active site is necessary for substrate induced dimer assembly in triosephosphate isomerase.

PubMed

Jimenez-Sandoval, Pedro; Vique-Sanchez, Jose Luis; Hidalgo, Marisol López; Velazquez-Juarez, Gilberto; Diaz-Quezada, Corina; Arroyo-Navarro, Luis Fernando; Moran, Gabriela Montero; Fattori, Juliana; Jessica Diaz-Salazar, A; Rudiño-Pinera, Enrique; Sotelo-Mundo, Rogerio; Figueira, Ana Carolina Migliorini; Lara-Gonzalez, Samuel; Benítez-Cardoza, Claudia G; Brieba, Luis G

2017-11-01

The protozoan parasite Trichomonas vaginalis contains two nearly identical triosephosphate isomerases (TvTIMs) that dissociate into stable monomers and dimerize upon substrate binding. Herein, we compare the role of the "ball and socket" and loop 3 interactions in substrate assisted dimer assembly in both TvTIMs. We found that point mutants at the "ball" are only 39 and 29-fold less catalytically active than their corresponding wild-type counterparts, whereas Δloop 3 deletions are 1502 and 9400-fold less active. Point and deletion mutants dissociate into stable monomers. However, point mutants assemble as catalytic competent dimers upon binding of the transition state substrate analog PGH, whereas loop 3 deletions remain monomeric. A comparison between crystal structures of point and loop 3 deletion monomeric mutants illustrates that the catalytic residues in point mutants and wild-type TvTIMs are maintained in the same orientation, whereas the catalytic residues in deletion mutants show an increase in thermal mobility and present structural disorder that may hamper their catalytic role. The high enzymatic activity present in monomeric point mutants correlates with the formation of dimeric TvTIMs upon substrate binding. In contrast, the low activity and lack of dimer assembly in deletion mutants suggests a role of loop 3 in promoting the formation of the active site as well as dimer assembly. Our results suggest that in TvTIMs the active site is assembled during dimerization and that the integrity of loop 3 and ball and socket residues is crucial to stabilize the dimer. Copyright © 2017 Elsevier B.V. All rights reserved.

TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation.

PubMed

Morioka, Sho; Broglie, Peter; Omori, Emily; Ikeda, Yuka; Takaesu, Giichi; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun

2014-02-17

TNF activates three distinct intracellular signaling cascades leading to cell survival, caspase-8-mediated apoptosis, or receptor interacting protein kinase 3 (RIPK3)-dependent necrosis, also called necroptosis. Depending on the cellular context, one of these pathways is activated upon TNF challenge. When caspase-8 is activated, it drives the apoptosis cascade and blocks RIPK3-dependent necrosis. Here we report the biological event switching to activate necrosis over apoptosis. TAK1 kinase is normally transiently activated upon TNF stimulation. We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. In addition, we also demonstrated that activation of RIPK1 and RIPK3 promoted TAK1 activation, suggesting a positive feedforward loop of RIPK1, RIPK3, and TAK1. Conversely, ablation of TAK1 caused caspase-dependent apoptosis, in which Ripk3 deletion did not block cell death either in vivo or in vitro. Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis.

Age and Structure of the Laschamp Geomagnetic Excursion

NASA Astrophysics Data System (ADS)

Scaillet, S.; Laj, C.; Kissel, C.; Guillou, H.; Singer, B. S.

2004-12-01

The age of the Laschamp geomagnetic excursion has been recently re-investigated using unspiked K/Ar and Ar/Ar techniques (Guillou et al., Session V01, this conference). The new age determination of 40.4 +/- 2.0 ka (2 sigma) is more precise than those previously reported in the literature and agrees precisely with that deduced from the GLOPIS-75 sedimentary paleointensity stack calibrated against the GISP2 ice core chronology. Two of the North Atlantic cores used in GLOPIS-75 (MD95-2034 and PS2644-5) yield rather detailed transitional VGP paths. In the two cases the paths show large similarities, with the VGP initially descending along mid-western Pacific, then returning to normal polarities with a large clockwise loop over Africa and Europe. Differences in the highest southern latitudes reached by the VGP can be explained assuming more different degrees of smearing of the paleomagnetic record due to differences in sedimentation rate in the two cores. In the most detailed record, MD95-2034 , two smaller loops are present preceding the main excursion. In the two cores, the excursion is characterized by a significant drop in intensity. The reversal paths observed for the Laschamp event are very close in position to those reported for the Icelandic Basin Event (IBE) from sites in the North Atlantic and the South China Sea (Laj et al., this conference) but differ in the sense of looping: while a clockwise loop is observed here, a counterclockwise loop is observed for the IBE. Despite this difference, the similarity of the transitional records tends to suggest that a similar, relatively simple, geometry has dominated the two excursions and therefore that similar dynamo mechanisms have prevailed during the reversal process.

Investigating the Response of Loop Plasma to Nanoflare Heating Using RADYN Simulations

NASA Astrophysics Data System (ADS)

Polito, V.; Testa, P.; Allred, J.; De Pontieu, B.; Carlsson, M.; Pereira, T. M. D.; Gošić, Milan; Reale, Fabio

2018-04-01

We present the results of 1D hydrodynamic simulations of coronal loops that are subject to nanoflares, caused by either in situ thermal heating or nonthermal electron (NTE) beams. The synthesized intensity and Doppler shifts can be directly compared with Interface Region Imaging Spectrograph (IRIS) and Atmospheric Imaging Assembly (AIA) observations of rapid variability in the transition region (TR) of coronal loops, associated with transient coronal heating. We find that NTEs with high enough low-energy cutoff ({E}{{C}}) deposit energy in the lower TR and chromosphere, causing blueshifts (up to ∼20 km s‑1) in the IRIS Si IV lines, which thermal conduction cannot reproduce. The {E}{{C}} threshold value for the blueshifts depends on the total energy of the events (≈5 keV for 1024 erg, up to 15 keV for 1025 erg). The observed footpoint emission intensity and flows, combined with the simulations, can provide constraints on both the energy of the heating event and {E}{{C}}. The response of the loop plasma to nanoflares depends crucially on the electron density: significant Si IV intensity enhancements and flows are observed only for initially low-density loops (<109 cm‑3). This provides a possible explanation of the relative scarcity of observations of significant moss variability. While the TR response to single heating episodes can be clearly observed, the predicted coronal emission (AIA 94 Å) for single strands is below current detectability and can only be observed when several strands are heated closely in time. Finally, we show that the analysis of the IRIS Mg II chromospheric lines can help further constrain the properties of the heating mechanisms.

Olfactory short-term memory encoding and maintenance - an event-related potential study.

PubMed

Lenk, Steffen; Bluschke, Annet; Beste, Christian; Iannilli, Emilia; Rößner, Veit; Hummel, Thomas; Bender, Stephan

2014-09-01

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model. Copyright © 2014 Elsevier Inc. All rights reserved.

Listening in on Friction: Stick-Slip Acoustical Signatures in Velcro

NASA Astrophysics Data System (ADS)

Hurtado Parra, Sebastian; Morrow, Leslie; Radziwanowski, Miles; Angiolillo, Paul

2013-03-01

The onset of kinetic friction and the possible resulting stick-slip motion remain mysterious phenomena. Moreover, stick-slip dynamics are typically accompanied by acoustic bursts that occur temporally with the slip event. The dry sliding dynamics of the hook-and-loop system, as exemplified by Velcro, manifest stick-slip behavior along with audible bursts that are easily micrphonically collected. Synchronized measurements of the friction force and acoustic emissions were collected as hooked Velcro was driven at constant velocity over a bed of looped Velcro in an anechoic chamber. Not surprising, the envelope of the acoustic bursts maps well onto the slip events of the friction force time series and the intensity of the bursts trends with the magnitude of the difference of the friction force during a stick-slip event. However, the analysis of the acoustic emission can serve as a sensitive tool for revealing some of the hidden details of the evolution of the transition from static to kinetic friction. For instance, small acoustic bursts are seen prior to the Amontons-Coulomb threshold, signaling precursor events prior to the onset of macroscopically observed motion. Preliminary spectral analysis of the acoustic emissions including intensity-frequency data will be presented.

Space Science

NASA Image and Video Library

2003-01-01

These banana-shaped loops are part of a computer-generated snapshot of our sun's magnetic field. The solar magnetic-field lines loop through the sun's corona, break through the sun's surface, and cornect regions of magnetic activity, such as sunspots. This image --part of a magnetic-field study of the sun by NASA's Allen Gary -- shows the outer portion (skins) of interconnecting systems of hot (2 million degrees Kelvin) coronal loops within and between two active magnetic regions on opposite sides of the sun's equator. The diameter of these coronal loops at their foot points is approximately the same size as the Earth's radius (about 6,000 kilometers).

Voluntary control of intracortical oscillations for reconfiguration of network activity

PubMed Central

Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

2016-01-01

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

The Propagation of Solar Energetic Particles as Observed by the Stereo Spacecraft and Near Earth

NASA Astrophysics Data System (ADS)

von Rosenvinge, T. T.; Richardson, I. G.; Cane, H. V.; Christian, E. R.; Cummings, A. C.; Cohen, C. M.; Leske, R. A.; Mewaldt, R. A.; Stone, E. C.; Wiedenbeck, M. E.

2014-12-01

Over 200 Solar Energetic Particle Events (SEPs) with protons > 25 MeV have been identified using data from the IMPACT HET telescopes on the STEREO A and B spacecraft and similar data from SoHO near Earth. The properties of these events are tabulated in a recent publication in Solar Physics (Richardson, et al., 2014). One of the goals of the Stereo Mission is to better understand the propagation of SEPs. The properties of events observed by multiple spacecraft on average are well-organized by the distance of the footpoints of the nominal Parker Spiral magnetic field lines passing the observing spacecraft from the parent active regions. However, some events deviate significantly from this pattern. For example, in events observed by three spacecraft, the spacecraft with the best nominal connection does not necessarily observe the highest intensity or earliest particle arrival time. We will search for such events and try to relate their behavior to non-nominal magnetic field patterns. We will look, for example, for the effects of the interplanetary current sheet, the influence of magnetic clouds which are thought to contain large magnetic loops with both ends connected to the sun (a large departure from the Parker spiral), and also whether particle propagation can be disrupted by the presence of interplanetary shocks. Reference: Richardson et al., Solar Phys. 289, 3059, 2014

Development of a generic GMCC simulator.

DOT National Transportation Integrated Search

2001-11-01

This document describes the development and current status of a high fidelity, human-in-the-loop simulator for Airway Facilities : Maintenance Control Centers and Operations Control Centers. Applications include Event Manager, Maintenance Automation ...

Identification of new members of the MAPK gene family in plants shows diverse conserved domains and novel activation loop variants.

PubMed

Mohanta, Tapan Kumar; Arora, Pankaj Kumar; Mohanta, Nibedita; Parida, Pratap; Bae, Hanhong

2015-02-06

Mitogen Activated Protein Kinase (MAPK) signaling is of critical importance in plants and other eukaryotic organisms. The MAPK cascade plays an indispensible role in the growth and development of plants, as well as in biotic and abiotic stress responses. The MAPKs are constitute the most downstream module of the three tier MAPK cascade and are phosphorylated by upstream MAP kinase kinases (MAPKK), which are in turn are phosphorylated by MAP kinase kinase kinase (MAPKKK). The MAPKs play pivotal roles in regulation of many cytoplasmic and nuclear substrates, thus regulating several biological processes. A total of 589 MAPKs genes were identified from the genome wide analysis of 40 species. The sequence analysis has revealed the presence of several N- and C-terminal conserved domains. The MAPKs were previously believed to be characterized by the presence of TEY/TDY activation loop motifs. The present study showed that, in addition to presence of activation loop TEY/TDY motifs, MAPKs are also contain MEY, TEM, TQM, TRM, TVY, TSY, TEC and TQY activation loop motifs. Phylogenetic analysis of all predicted MAPKs were clustered into six different groups (group A, B, C, D, E and F), and all predicted MAPKs were assigned with specific names based on their orthology based evolutionary relationships with Arabidopsis or Oryza MAPKs. We conducted global analysis of the MAPK gene family of plants from lower eukaryotes to higher eukaryotes and analyzed their genomic and evolutionary aspects. Our study showed the presence of several new activation loop motifs and diverse conserved domains in MAPKs. Advance study of newly identified activation loop motifs can provide further information regarding the downstream signaling cascade activated in response to a wide array of stress conditions, as well as plant growth and development.

Binding of DNA hairpins to an assembler-strand as part of a primordial translation device

NASA Astrophysics Data System (ADS)

Baumann, Ulrich

1987-09-01

A crucial event in the process leading to the origin of life is the emergence of a simple translation device. To approach experimental realization of this device the binding ability of short DNA hairpins to complementary oligonucleotides fixed on a solid support was investigated. The binding is achieved by base pairing between the loop nucleotides of the hairpins containing different numbers of adenosine residues and oligothymidylates covalently linked to cellulose. The loop has to consist of at least five nucleotides to achieve binding. The exact number of established base pairs was determined in two ways. First, the elution temperatures of hairpins and those of oligoadenylates which had the length of the loop were compared. Secondly, the architecture of the loop was analyzed by means of the single-strand-specific nuclease from mung bean acting as structural probe. Onlyn-2 of n loop nucleotides of a hairpin are able to form base pairs. Therefore, a strong evidence for the formation of a triplet of base pairs between primeval tRNA and mRNA sufficient to stabilize the complex enzyme-free is given.

Current systems of coronal loops in 3D MHD simulations

NASA Astrophysics Data System (ADS)

Warnecke, J.; Chen, F.; Bingert, S.; Peter, H.

2017-11-01

Aims: We study the magnetic field and current structure associated with a coronal loop. Through this we investigate to what extent the assumptions of a force-free magnetic field break down and where they might be justified. Methods: We analyze a three-dimensional (3D) magnetohydrodynamic (MHD) model of the solar corona in an emerging active region with the focus on the structure of the forming coronal loops. The lower boundary of this simulation is taken from a model of an emerging active region. As a consequence of the emerging magnetic flux and the horizontal motions at the surface a coronal loop forms self-consistently. We investigate the current density along magnetic field lines inside (and outside) this loop and study the magnetic and plasma properties in and around this loop. The loop is defined as the bundle of field lines that coincides with enhanced emission in extreme UV. Results: We find that the total current along the emerging loop changes its sign from being antiparallel to parallel to the magnetic field. This is caused by the inclination of the loop together with the footpoint motion. Around the loop, the currents form a complex non-force-free helical structure. This is directly related to a bipolar current structure at the loop footpoints at the base of the corona and a local reduction of the background magnetic field (I.e., outside the loop) caused by the plasma flow into and along the loop. Furthermore, the locally reduced magnetic pressure in the loop allows the loop to sustain a higher density, which is crucial for the emission in extreme UV. The action of the flow on the magnetic field hosting the loop turns out to also be responsible for the observed squashing of the loop. Conclusions: The complex magnetic field and current system surrounding it can only be modeled in 3D MHD models where the magnetic field has to balance the plasma pressure. A one-dimensional coronal loop model or a force-free extrapolation cannot capture the current system and the complex interaction of the plasma and the magnetic field in the coronal loop, despite the fact that the loop is under low-β conditions.

[Design of medical devices management system supporting full life-cycle process management].

PubMed

Su, Peng; Zhong, Jianping

2014-03-01

Based on the analysis of the present status of medical devices management, this paper optimized management process, developed a medical devices management system with Web technologies. With information technology to dynamic master the use of state of the entire life-cycle of medical devices. Through the closed-loop management with pre-event budget, mid-event control and after-event analysis, improved the delicacy management level of medical devices, optimized asset allocation, promoted positive operation of devices.

syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

PubMed Central

El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

1997-01-01

Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

Understanding the connection between the energy released during solar flares and their emission in the lower atmosphere

NASA Astrophysics Data System (ADS)

da Costa, F. Rubio

2017-10-01

While progress has been made on understanding how energy is released and deposited along the solar atmosphere during explosive events such as solar flares, the chromospheric and coronal heating through the sudden release of magnetic energy remain an open problem in solar physics. Recent hydrodynamic models allow to investigate the energy deposition along a flare loop and to study the response of the chromosphere. These results have been improved with the consideration of transport and acceleration of particles along the loop. RHESSI and Fermi/GBM X-ray and gamma-ray observations help to constrain the spectral properties of the injected electrons. The excellent spatial, spectral and temporal resolution of IRIS will also help us to constrain properties of explosive events, such as the continuum emission during flares or their emission in the chromosphere.

A Decentralized Event-Triggered Dissipative Control Scheme for Systems With Multiple Sensors to Sample the System Outputs.

PubMed

Zhang, Xian-Ming; Han, Qing-Long

2016-12-01

This paper is concerned with decentralized event-triggered dissipative control for systems with the entries of the system outputs having different physical properties. Depending on these different physical properties, the entries of the system outputs are grouped into multiple nodes. A number of sensors are used to sample the signals from different nodes. A decentralized event-triggering scheme is introduced to select those necessary sampled-data packets to be transmitted so that communication resources can be saved significantly while preserving the prescribed closed-loop performance. First, in order to organize the decentralized data packets transmitted from the sensor nodes, a data packet processor (DPP) is used to generate a new signal to be held by the zero-order-hold once the signal stored by the DPP is updated at some time instant. Second, under the mechanism of the DPP, the resulting closed-loop system is modeled as a linear system with an interval time-varying delay. A sufficient condition is derived such that the closed-loop system is asymptotically stable and strictly (Q 0 ,S 0 ,R 0 ) -dissipative, where Q 0 ,S 0 , and R 0 are real matrices of appropriate dimensions with Q 0 and R 0 symmetric. Third, suitable output-based controllers can be designed based on solutions to a set of a linear matrix inequality. Finally, two examples are given to demonstrate the effectiveness of the proposed method.

Quasi-periodic Reversals of Radio Polarization at 17 GHz Observed in the 2002 April 21 Solar Event

NASA Astrophysics Data System (ADS)

Huang, Guangli; Lin, Jun

2006-03-01

We investigate high spatial resolution radio polarization data obtained by the Nobeyama Radioheliograph (NoRH) and high time resolution data observed with the Nobeyama Radio Polarimeters (NoRP) during the well-studied flare/CME event of 2002 April 21. A 17 GHz radio source at the loop top was seen by NoRH to move upward together with the expanding flare loops at a speed of around 10 km s-1. In the 5 minutes before the source began its upward motion, the Stokes V of the radio signals at 17 GHz showed quasi-periodic reversals between left-circular polarization (LCP) and right-circular polarization (RCP). Following this interval, the polarizations gradually turned to LCP. During this period, the polarization of the corresponding footpoint source maintained the RCP sense. The reversal of Stokes V between RCP and LCP was also detected at lower frequencies (1-2 GHz) by NoRP, without spatial resolution. The observed reversals between RCP and LCP of the radio signals from the top of the flare loop system can be taken as evidence that magnetic energy is released or energetic particles are produced at the magnetic reconnection site in a quasi-periodic fashion.

Plant STAND P-loop NTPases: a current perspective of genome distribution, evolution, and function : Plant STAND P-loop NTPases: genomic organization, evolution, and molecular mechanism models contribute broadly to plant pathogen defense.

PubMed

Arya, Preeti; Acharya, Vishal

2018-02-01

STAND P-loop NTPase is the common weapon used by plant and other organisms from all three kingdoms of life to defend themselves against pathogen invasion. The purpose of this study is to review comprehensively the latest finding of plant STAND P-loop NTPase related to their genomic distribution, evolution, and their mechanism of action. Earlier, the plant STAND P-loop NTPase known to be comprised of only NBS-LRRs/AP-ATPase/NB-ARC ATPase. However, recent finding suggests that genome of early green plants comprised of two types of STAND P-loop NTPases: (1) mammalian NACHT NTPases and (2) NBS-LRRs. Moreover, YchF (unconventional G protein and members of P-loop NTPase) subfamily has been reported to be exceptionally involved in biotic stress (in case of Oryza sativa), thereby a novel member of STAND P-loop NTPase in green plants. The lineage-specific expansion and genome duplication events are responsible for abundance of plant STAND P-loop NTPases; where "moderate tandem and low segmental duplication" trajectory followed in majority of plant species with few exception (equal contribution of tandem and segmental duplication). Since the past decades, systematic research is being investigated into NBS-LRR function supported the direct recognition of pathogen or pathogen effectors by the latest models proposed via 'integrated decoy' or 'sensor domains' model. Here, we integrate the recently published findings together with the previous literature on the genomic distribution, evolution, and distinct models proposed for functional molecular mechanism of plant STAND P-loop NTPases.

Abundances, Ionization States, Temperatures, and FIP in Solar Energetic Particles

NASA Astrophysics Data System (ADS)

Reames, Donald V.

2018-04-01

The relative abundances of chemical elements and isotopes have been our most effective tool in identifying and understanding the physical processes that control populations of energetic particles. The early surprise in solar energetic particles (SEPs) was 1000-fold enhancements in {}3He/{}4He from resonant wave-particle interactions in the small "impulsive" SEP events that emit electron beams that produce type III radio bursts. Further studies found enhancements in Fe/O, then extreme enhancements in element abundances that increase with mass-to-charge ratio A/Q, rising by a factor of 1000 from He to Au or Pb arising in magnetic reconnection regions on open field lines in solar jets. In contrast, in the largest SEP events, the "gradual" events, acceleration occurs at shock waves driven out from the Sun by fast, wide coronal mass ejections (CMEs). Averaging many events provides a measure of solar coronal abundances, but A/Q-dependent scattering during transport causes variations with time; thus if Fe scatters less than O, Fe/O is enhanced early and depleted later. To complicate matters, shock waves often reaccelerate impulsive suprathermal ions left over or trapped above active regions that have spawned many impulsive events. Direct measurements of ionization states Q show coronal temperatures of 1-2 MK for most gradual events, but impulsive events often show stripping by matter traversal after acceleration. Direct measurements of Q are difficult and often unavailable. Since both impulsive and gradual SEP events have abundance enhancements that vary as powers of A/Q, we can use abundances to deduce the probable Q-values and the source plasma temperatures during acceleration, ≈3 MK for impulsive SEPs. This new technique also allows multiple spacecraft to measure temperature variations across the face of a shock wave, measurements otherwise unavailable and provides a new understanding of abundance variations in the element He. Comparing coronal abundances from SEPs and from the slow solar wind as a function of the first ionization potential (FIP) of the elements, remaining differences are for the elements C, P, and S. The theory of the fractionation of ions by Alfvén waves shows that C, P, and S are suppressed because of wave resonances during chromospheric transport on closed magnetic loops but not on open magnetic fields that supply the solar wind. Shock waves can accelerate ions from closed coronal loops that easily escape as SEPs, while the solar wind must emerge on open fields.

Brightness and magnetic evolution of solar coronal bright points

NASA Astrophysics Data System (ADS)

Ugarte-Urra, I.

2004-12-01

This thesis presents a study of the brightness and magnetic evolution of several Extreme ultraviolet (EUV) coronal bright points (hereafter BPs). BPs are loop-like features of enhanced emission in the coronal EUV and X-ray images of the Sun, that are associated to the interaction of opposite photospheric magnetic polarities with magnetic fluxes of ≈1018 - 1019 Mx. The study was carried out using several instruments on board the Solar and Heliospheric Observatory (SOHO): the Extreme Ultraviolet Imager (EIT), the Coronal Diagnostic Spectrometer (CDS) and the Michelson Doppler Imager (MDI), supported by the high resolution imaging from the Transition Region And Coronal Explorer (TRACE). The results confirm that, down to 1'' (i.e. ~715 km) resolution, BPs are made of small loops with lengths of ~6 Mm and cross-sections of ~2 Mm. The loops are very dynamic, evolving in time scales as short as 1 - 2 minutes. This is reflected in a highly variable EUV response with fluctuations highly correlated in spectral lines at transition region temperatures (in the range 3.2x10^4 - 3.5x10^5 K), but not always at coronal temperatures. A wavelet analysis of the intensity variations reveals, for the first time, the existence of quasi-periodic oscillations with periods ranging 400 -- 1000 s, in the range of periods characteristic of the chromospheric network. The link between BPs and network bright points is discussed, as well as the interpretation of the oscillations in terms of global acoustic modes of closed magnetic structures. A comparison of the magnetic flux evolution of the magnetic polarities to the EUV flux changes is also presented. Throughout their lifetime, the intrinsic EUV emission of BPs is found to be dependent on the total magnetic flux of the polarities. In short time scales, co-spatial and co-temporal TRACE and MDI images, reveal the signature of heating events that produce sudden EUV brightenings simultaneous to magnetic flux cancellations. This is interpreted in terms of magnetic reconnection events. Finally, a electron density study of six coronal bright points produces values of ~1.6x109 cm-3, closer to active region plasma than to quiet Sun. The analysis of a large coronal loop (half length of 72 Mm) introduces the discussion on the prospects of future plasma diagnostics of BPs with forthcoming solar missions like Solar-B.

Magnetic Field Configuration of Active Region NOAA 6555 at the Time of a Long Duration Flare on 23 March 1991: An Exception to Standard Flare Reconnection Model

NASA Technical Reports Server (NTRS)

Choudhary, Debi Prasad; Gary, Allen G.

1998-01-01

The high-resolution H(sub alpha) images observed during the decay phase of a long duration flare on 23 March 1991 are used to study the three-dimensional magnetic field configuration of the active region NOAA 6555. Whereas, all the large flares in NOAA 6555 occurred at the location of high magnetic shear and flux emergence, this long duration flare was observed in the region of low magnetic shear at the photosphere. The H(sub alpha) loop activity started soon after the maximum phase of the flare. There were few long loop at the initial phase of the activity. Some of these were sheared in the chromosphere at an angle of about 45 deg with the east-west axis. Gradually, increasing number of shorter loops, oriented along the east-west axis, started appearing. The chromospheric Dopplergrams show blue-shifts at the end points of the loops. By using different magnetic field models, we have extrapolated the photospheric magnetograms to the chromospheric heights. The magnetic field lines computed by using the potential field model correspond to most of the observed H(sub alpha) loops. The height of the H(sub alpha) loops were derived by comparing them with the computed field lines. From the temporal evolution of the H(sub alpha) loop activity, we derive the negative rate of appearance of H(sub alpha) features as a function of height. It is found that the field lines oriented along one of the neutral lines was sheared and low lying. The higher field lines were mostly potential. The paper also outlines a possible scenario for describing the post-flare stage of the observed long duration flare.

The Activation Domain of the Bovine Papillomavirus E2 Protein Mediates Association of DNA-Bound Dimers to form DNA Loops

NASA Astrophysics Data System (ADS)

Knight, Jonathan D.; Li, Rong; Botchan, Michael

1991-04-01

The E2 transactivator protein of bovine papillomavirus binds its specific DNA target sequence as a dimer. We have found that E2 dimers, performed in solution independent of DNA, exhibit substantial cooperativity of DNA binding as detected by both nitrocellulose filter retention and footprint analysis techniques. If the binding sites are widely spaced, E2 forms stable DNA loops visible by electron microscopy. When three widely separated binding sites reside on te DNA, E2 condenses the molecule into a bow-tie structure. This implies that each E2 dimer has at least two independent surfaces for multimerization. Two naturally occurring shorter forms of the protein, E2C and D8/E2, which function in vivo as repressors of transcription, do not form such loops. Thus, the looping function of E2 maps to the 161-amino acid activation domain. These results support the looping model of transcription activation by enhancers.

A Conserved Surface Loop in Type I Dehydroquinate Dehydratases Positions an Active Site Arginine and Functions in Substrate Binding

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

Light, Samuel H.; Minasov, George; Shuvalova, Ludmilla

2012-04-18

Dehydroquinate dehydratase (DHQD) catalyzes the third step in the biosynthetic shikimate pathway. We present three crystal structures of the Salmonella enterica type I DHQD that address the functionality of a surface loop that is observed to close over the active site following substrate binding. Two wild-type structures with differing loop conformations and kinetic and structural studies of a mutant provide evidence of both direct and indirect mechanisms of involvement of the loop in substrate binding. In addition to allowing amino acid side chains to establish a direct interaction with the substrate, closure of the loop necessitates a conformational change ofmore » a key active site arginine, which in turn positions the substrate productively. The absence of DHQD in humans and its essentiality in many pathogenic bacteria make the enzyme a target for the development of nontoxic antimicrobials. The structures and ligand binding insights presented here may inform the design of novel type I DHQD inhibiting molecules.« less

A small-scale eruption leading to a blowout macrospicule jet in an on-disk coronal hole

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

Adams, Mitzi; Sterling, Alphonse C.; Moore, Ronald L.

2014-03-01

We examine the three-dimensional magnetic structure and dynamics of a solar EUV-macrospicule jet that occurred on 2011 February 27 in an on-disk coronal hole. The observations are from the Solar Dynamics Observatory (SDO) Atmospheric Imaging Assembly (AIA) and the SDO Helioseismic and Magnetic Imager (HMI). The observations reveal that in this event, closed-field-carrying cool absorbing plasma, as in an erupting mini-filament, erupted and opened, forming a blowout jet. Contrary to some jet models, there was no substantial recently emerged, closed, bipolar-magnetic field in the base of the jet. Instead, over several hours, flux convergence and cancellation at the polarity inversionmore » line inside an evolved arcade in the base apparently destabilized the entire arcade, including its cool-plasma-carrying core field, to undergo a blowout eruption in the manner of many standard-sized, arcade-blowout eruptions that produce a flare and coronal mass ejection. Internal reconnection made bright 'flare' loops over the polarity inversion line inside the blowing-out arcade field, and external reconnection of the blowing-out arcade field with an ambient open field made longer and dimmer EUV loops on the outside of the blowing-out arcade. That the loops made by the external reconnection were much larger than the loops made by the internal reconnection makes this event a new variety of blowout jet, a variety not recognized in previous observations and models of blowout jets.« less

Closed-Loop and Activity-Guided Optogenetic Control

PubMed Central

Grosenick, Logan; Marshel, James H.; Deisseroth, Karl

2016-01-01

Advances in optical manipulation and observation of neural activity have set the stage for widespread implementation of closed-loop and activity-guided optical control of neural circuit dynamics. Closing the loop optogenetically (i.e., basing optogenetic stimulation on simultaneously observed dynamics in a principled way) is a powerful strategy for causal investigation of neural circuitry. In particular, observing and feeding back the effects of circuit interventions on physiologically relevant timescales is valuable for directly testing whether inferred models of dynamics, connectivity, and causation are accurate in vivo. Here we highlight technical and theoretical foundations as well as recent advances and opportunities in this area, and we review in detail the known caveats and limitations of optogenetic experimentation in the context of addressing these challenges with closed-loop optogenetic control in behaving animals. PMID:25856490

How do postgraduate GP trainees regulate their learning and what helps and hinders them? A qualitative study.

PubMed

Sagasser, Margaretha H; Kramer, Anneke W M; van der Vleuten, Cees P M

2012-08-06

Self-regulation is essential for professional development. It involves monitoring of performance, identifying domains for improvement, undertaking learning activities, applying newly learned knowledge and skills and self-assessing performance. Since self-assessment alone is ineffective in identifying weaknesses, learners should seek external feedback too. Externally regulated educational interventions, like reflection, learning portfolios, assessments and progress meetings, are increasingly used to scaffold self-regulation.The aim of this study is to explore how postgraduate trainees regulate their learning in the workplace, how external regulation promotes self-regulation and which elements facilitate or impede self-regulation and learning. In a qualitative study with a phenomenologic approach we interviewed first- and third-year GP trainees from two universities in the Netherlands. Twenty-one verbatim transcripts were coded. Through iterative discussion the researchers agreed on the interpretation of the data and saturation was reached. Trainees used a short and a long self-regulation loop. The short loop took one week at most and was focused on problems that were easy to resolve and needed minor learning activities. The long loop was focused on complex or recurring problems needing multiple and planned longitudinal learning activities. External assessments and formal training affected the long but not the short loop. The supervisor had a facilitating role in both loops. Self-confidence was used to gauge competence.Elements influencing self-regulation were classified into three dimensions: personal (strong motivation to become a good doctor), interpersonal (stimulation from others) and contextual (organizational and educational features). Trainees did purposefully self-regulate their learning. Learning in the short loop may not be visible to others. Trainees should be encouraged to actively seek and use external feedback in both loops. An important question for further research is which educational interventions might be used to scaffold learning in the short loop. Investing in supervisor quality remains important, since they are close to trainee learning in both loops.

How do postgraduate GP trainees regulate their learning and what helps and hinders them? A qualitative study

PubMed Central

2012-01-01

Background Self-regulation is essential for professional development. It involves monitoring of performance, identifying domains for improvement, undertaking learning activities, applying newly learned knowledge and skills and self-assessing performance. Since self-assessment alone is ineffective in identifying weaknesses, learners should seek external feedback too. Externally regulated educational interventions, like reflection, learning portfolios, assessments and progress meetings, are increasingly used to scaffold self-regulation. The aim of this study is to explore how postgraduate trainees regulate their learning in the workplace, how external regulation promotes self-regulation and which elements facilitate or impede self-regulation and learning. Methods In a qualitative study with a phenomenologic approach we interviewed first- and third-year GP trainees from two universities in the Netherlands. Twenty-one verbatim transcripts were coded. Through iterative discussion the researchers agreed on the interpretation of the data and saturation was reached. Results Trainees used a short and a long self-regulation loop. The short loop took one week at most and was focused on problems that were easy to resolve and needed minor learning activities. The long loop was focused on complex or recurring problems needing multiple and planned longitudinal learning activities. External assessments and formal training affected the long but not the short loop. The supervisor had a facilitating role in both loops. Self-confidence was used to gauge competence.Elements influencing self-regulation were classified into three dimensions: personal (strong motivation to become a good doctor), interpersonal (stimulation from others) and contextual (organizational and educational features). Conclusions Trainees did purposefully self-regulate their learning. Learning in the short loop may not be visible to others. Trainees should be encouraged to actively seek and use external feedback in both loops. An important question for further research is which educational interventions might be used to scaffold learning in the short loop. Investing in supervisor quality remains important, since they are close to trainee learning in both loops. PMID:22866981

Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL.

PubMed

Zhou, Yan; Kurukuti, Sreenivasulu; Saffrey, Peter; Vukovic, Milica; Michie, Alison M; Strogantsev, Ruslan; West, Adam G; Vetrie, David

2013-12-19

TAL1 is an important regulator of hematopoiesis and its expression is tightly controlled despite complexities in its genomic organization. It is frequently misregulated in T-cell acute lymphoblastic leukemia (T-ALL), often due to deletions between TAL1 and the neighboring STIL gene. To better understand the events that lead to TAL1 expression in hematopoiesis and in T-ALL, we studied looping interactions at the TAL1 locus. In TAL1-expressing erythroid cells, the locus adopts a looping "hub" which brings into close physical proximity all known TAL1 cis-regulatory elements including CTCF-bound insulators. Loss of GATA1 results in disassembly of the hub and loss of CTCF/RAD21 from one of its insulators. Genes flanking TAL1 are partly dependent on hub integrity for their transcriptional regulation. We identified looping patterns unique to TAL1-expressing T-ALL cells, and, intriguingly, loops occurring between the TAL1 and STIL genes at the common TAL1/STIL breakpoints found in T-ALL. These findings redefine how TAL1 and neighboring genes communicate within the nucleus, and indicate that looping facilitates both normal and aberrant TAL1 expression and may predispose to structural rearrangements in T-ALL. We also propose that GATA1-dependent looping mechanisms may facilitate the conservation of TAL1 regulation despite cis-regulatory remodeling during vertebrate evolution.

Computer Generated Snapshot of Our Sun's Magnetic Field

NASA Technical Reports Server (NTRS)

2003-01-01

These banana-shaped loops are part of a computer-generated snapshot of our sun's magnetic field. The solar magnetic-field lines loop through the sun's corona, break through the sun's surface, and cornect regions of magnetic activity, such as sunspots. This image --part of a magnetic-field study of the sun by NASA's Allen Gary -- shows the outer portion (skins) of interconnecting systems of hot (2 million degrees Kelvin) coronal loops within and between two active magnetic regions on opposite sides of the sun's equator. The diameter of these coronal loops at their foot points is approximately the same size as the Earth's radius (about 6,000 kilometers).

Crew Survivability After a Rapid Cabin Depressurization Event

NASA Technical Reports Server (NTRS)

Sargusingh, Miriam J.

2012-01-01

Anecdotal evidence acquired through historic failure investigations involving rapid cabin decompression (e.g. Challenger, Columbia and Soyuz 11) show that full evacuation of the cabin atmosphere may occur within seconds. During such an event, the delta-pressure between the sealed suit ventilation system and the cabin will rise at the rate of the cabin depressurization; potentially at a rate exceeding the capability of the suit relief valve. It is possible that permanent damage to the suit pressure enclosure and ventilation loop components may occur as the integrated system may be subjected to delta pressures in excess of the design-to pressures. Additionally, as the total pressure of the suit ventilation system decreases, so does the oxygen available to the crew. The crew may be subjected to a temporarily incapacitating, but non-lethal, hypoxic environment. It is expected that the suit will maintain a survivable atmosphere on the crew until the vehicle pressure control system recovers or the cabin has otherwise attained a habitable environment. A common finding from the aforementioned reports indicates that the crew would have had a better chance at surviving the event had they been in a protective configuration, that is, in a survival suit. Making use of these lessons learned, the Constellation Program implemented a suit loop in the spacecraft design and required that the crew be in a protective configuration, that is suited with gloves on and visors down, during dynamic phases of flight that pose the greatest risk for a rapid and uncontrolled cabin depressurization event: ascent, entry, and docking. This paper details the evaluation performed to derive suit pressure garment and ventilation system performance parameters that would lead to the highest probability of crew survivability after an uncontrolled crew cabin depressurization event while remaining in the realm of practicality for suit design. This evaluation involved: (1) assessment of stakeholder expectations to validate the functionality being imposed; (2) review/refinement of concept of operations to establish the potential triggers for such an event and define the response of the spacecraft and suit ventilation loop pressure control systems; and (3) assessment of system capabilities with respect to structural capability and pressure control.

The 26 December 2001 Solar Event Responsible for GLE63. I. Observations of a Major Long-Duration Flare with the Siberian Solar Radio Telescope

NASA Astrophysics Data System (ADS)

Grechnev, V. V.; Kochanov, A. A.

2016-12-01

Ground level enhancements (GLEs) of cosmic-ray intensity occur, on average, once a year. Because they are rare, studying the solar sources of GLEs is especially important to approach understanding their origin. The SOL2001-12-26 eruptive-flare event responsible for GLE63 seems to be challenging in some aspects. Deficient observations limited our understanding of it. Analysis of additional observations found for this event provided new results that shed light on the flare configuration and evolution. This article addresses the observations of this flare with the Siberian Solar Radio Telescope (SSRT). Taking advantage of its instrumental characteristics, we analyze the detailed SSRT observations of a major long-duration flare at 5.7 GHz without cleaning the images. The analysis confirms that the source of GLE63 was associated with an event in active region 9742 that comprised two flares. The first flare (04:30 - 05:03 UT) reached a GOES importance of about M1.6. Two microwave sources were observed, whose brightness temperatures at 5.7 GHz exceeded 10 MK. The main flare, up to an importance of M7.1, started at 05:04 UT and occurred in strong magnetic fields. The observed microwave sources reached a brightness temperature of about 250 MK. They were not static. After appearing on the weaker-field periphery of the active region, the microwave sources moved toward each other nearly along the magnetic neutral line, approaching the stronger-field core of the active region, and then moved away from the neutral line like expanding ribbons. These motions rule out an association of the non-thermal microwave sources with a single flaring loop.

Switch loop flexibility affects substrate transport of the AcrB efflux pump

DOE PAGES

Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea; ...

2017-10-05

The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutionsmore » on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.« less

Switch loop flexibility affects substrate transport of the AcrB efflux pump

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

Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea

The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutionsmore » on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.« less

A dynamic mechanism for allosteric activation of Aurora kinase A by activation loop phosphorylation.

PubMed

Ruff, Emily F; Muretta, Joseph M; Thompson, Andrew R; Lake, Eric W; Cyphers, Soreen; Albanese, Steven K; Hanson, Sonya M; Behr, Julie M; Thomas, David D; Chodera, John D; Levinson, Nicholas M

2018-02-21

Many eukaryotic protein kinases are activated by phosphorylation on a specific conserved residue in the regulatory activation loop, a post-translational modification thought to stabilize the active DFG-In state of the catalytic domain. Here we use a battery of spectroscopic methods that track different catalytic elements of the kinase domain to show that the ~100 fold activation of the mitotic kinase Aurora A (AurA) by phosphorylation occurs without a population shift from the DFG-Out to the DFG-In state, and that the activation loop of the activated kinase remains highly dynamic. Instead, molecular dynamics simulations and electron paramagnetic resonance experiments show that phosphorylation triggers a switch within the DFG-In subpopulation from an autoinhibited DFG-In substate to an active DFG-In substate, leading to catalytic activation. This mechanism raises new questions about the functional role of the DFG-Out state in protein kinases. © 2018, Ruff et al.

Identification and characterization of the sodium-binding site of activated protein C.

PubMed

He, X; Rezaie, A R

1999-02-19

Activated protein C (APC) requires both Ca2+ and Na+ for its optimal catalytic function. In contrast to the Ca2+-binding sites, the Na+-binding site(s) of APC has not been identified. Based on a recent study with thrombin, the 221-225 loop is predicted to be a potential Na+-binding site in APC. The sequence of this loop is not conserved in trypsin. We engineered a Gla domainless form of protein C (GDPC) in which the 221-225 loop was replaced with the corresponding loop of trypsin. We found that activated GDPC (aGDPC) required Na+ (or other alkali cations) for its amidolytic activity with dissociation constant (Kd(app)) = 44.1 +/- 8.6 mM. In the presence of Ca2+, however, the requirement for Na+ by aGDPC was eliminated, and Na+ stimulated the cleavage rate 5-6-fold with Kd(app) = 2.3 +/- 0.3 mM. Both cations were required for efficient factor Va inactivation by aGDPC. In the presence of Ca2+, the catalytic function of the mutant was independent of Na+. Unlike aGDPC, the mutant did not discriminate among monovalent cations. We conclude that the 221-225 loop is a Na+-binding site in APC and that an allosteric link between the Na+ and Ca2+ binding loops modulates the structure and function of this anticoagulant enzyme.

Active stabilization of a rapidly chirped laser by an optoelectronic digital servo-loop control.

PubMed

Gorju, G; Jucha, A; Jain, A; Crozatier, V; Lorgeré, I; Le Gouët, J-L; Bretenaker, F; Colice, M

2007-03-01

We propose and demonstrate a novel active stabilization scheme for wide and fast frequency chirps. The system measures the laser instantaneous frequency deviation from a perfectly linear chirp, thanks to a digital phase detection process, and provides an error signal that is used to servo-loop control the chirped laser. This way, the frequency errors affecting a laser scan over 10 GHz on the millisecond timescale are drastically reduced below 100 kHz. This active optoelectronic digital servo-loop control opens new and interesting perspectives in fields where rapidly chirped lasers are crucial.

Te homogeneous precipitation in Ge dislocation loop vicinity

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

Perrin Toinin, J.; Portavoce, A., E-mail: alain.portavoce@im2np.fr; Texier, M.

2016-06-06

High resolution microscopies were used to study the interactions of Te atoms with Ge dislocation loops, after a standard n-type doping process in Ge. Te atoms neither segregate nor precipitate on dislocation loops, but form Te-Ge clusters at the same depth as dislocation loops, in contradiction with usual dopant behavior and thermodynamic expectations. Atomistic kinetic Monte Carlo simulations show that Te atoms are repulsed from dislocation loops due to elastic interactions, promoting homogeneous Te-Ge nucleation between dislocation loops. This phenomenon is enhanced by coulombic interactions between activated Te{sup 2+} or Te{sup 1+} ions.

Mechanism of autophosphorylation of mycobacterial PknB explored by molecular dynamics simulations.

PubMed

Damle, Nikhil P; Mohanty, Debasisa

2014-07-22

Mycobacterial Ser/Thr kinase, PknB, is essential for the growth of the pathogen. Unphosphorylated PknB is catalytically inactive, and its activation requires autophosphorylation of Thr residues on the activation loop. Autophosphorylation can in principle take place via two distinct mechanisms. Intermolecular trans autophosphorylation involves dimerization and phosphorylation of the activation loop of one chain in the catalytic pocket of the other chain. On the other hand, intramolecular cis autophosphorylation involves phosphorylation of the activation loop of the kinases in its own catalytic pocket within a monomer. On the basis of the crystal structure of PknB in the front-to-front dimeric form, it is currently believed that activation of PknB involves trans autophosphorylation. However, because of the lack of coordinates of the activation loop in the crystal structures, atomic details of the conformational changes associated with activation are yet to be deciphered. Therefore, to understand the conformational transitions associated with activation via autophosphorylation, a series of explicit solvent molecular dynamics simulations with a duration of 1 μs have been performed on each of the phosphorylated and nonphosphorylated forms of the PknB catalytic domain in monomeric and dimeric states. Simulations on phosphorylated PknB revealed a differential network of crucial electrostatic and hydrophobic residues that stabilize the phosphorylated form in the active conformation. Interestingly, in our simulations on nonphosphorylated monomers, the activation loop was observed to fold into its own active site, thereby opening the novel possibility of activation through intramolecular cis autophosphorylation. Thus, our simulations suggest that autophosphorylation of PknB might also involve cis initiation followed by trans amplification as reported for other eukaryotic kinases based on recent reaction kinetics studies.

Electron Spectral Breaking Caused by Magnetic Reconnection in Impulsive Flare Events

NASA Astrophysics Data System (ADS)

Tan, Lun C.

2018-05-01

Using data from the Wind/3D Plasma and Energetic Particle (3DP) instrument, we have analyzed the energy spectral difference of low-energy electrons between the “impulsive” and “gradual” solar energetic particle (SEP) events during solar cycle 23. Since simulations reveal that in the exhaust of magnetic reconnection sites, electrons could form a beam structure in which the parallel speed is limited by the electron Alfvén speed (V Ae), their spectral steepening should be observable at the electron energy E e, corresponding to V Ae. In addition, the analysis of transversely oscillating coronal loops shows that in the loop-top region, where the reconnection site is located, V Ae corresponds to E e < 15 keV. We hence search for the spectral steepening of electrons in this E e range. In our search we have taken the effect of local particle acceleration at reconnecting current sheets into consideration. The effect may occur in the solar wind and impact the observed time-intensity profiles of SEPs. Our analysis shows that in the impulsive flare event, the electron spectral steepening occurs at E e = 7 ± 2 keV, whereas no steepening is seen in the gradual event. Therefore, the comparison between the impulsive and gradual SEP event lists provided by this work could be important for future investigations of particle acceleration in the corona and the solar wind.

Assessment and Accommodation of Thermal Expansion of the Internal Active Thermal Control System Coolant During Launch to On-Orbit Activation of International Space Station Elements

NASA Technical Reports Server (NTRS)

Edwards, Darryl; Ungar, Eugene K.; Holt, James M.

2002-01-01

The International Space Station (ISS) employs an Internal Active Thermal Control System (IATCS) comprised of several single-phase water coolant loops. These coolant loops are distributed throughout the ISS pressurized elements. The primary element coolant loops (i.e. U.S. Laboratory module) contain a fluid accumulator to accomodate thermal expansion of the system. Other element coolant loops are parasitic (i.e. Airlock), have no accumulator, and require an alternative approach to insure that the system maximum design pressure (MDP) is not exceeded during the Launch to Activation (LTA) phase. During this time the element loops is a stand alone closed system. The solution approach for accomodating thermal expansion was affected by interactions of system components and their particular limitations. The mathematical solution approach was challenged by the presence of certain unknown or not readily obtainable physical and thermodynamic characteristics of some system components and processes. The purpose of this paper is to provide a brief description of a few of the solutions that evolved over time, a novel mathematical solution to eliminate some of the unknowns or derive the unknowns experimentally, and the testing and methods undertaken.

Assessment and Accommodation of Thermal Expansion of the Internal Active Thermal Control System Coolant During Launch to On-Orbit Activation of International Space Station Elements

NASA Technical Reports Server (NTRS)

Edwards, J. Darryl; Ungar, Eugene K.; Holt, James M.; Turner, Larry D. (Technical Monitor)

2001-01-01

The International Space Station (ISS) employs an Internal Active Thermal Control System (IATCS) comprised of several single-phase water coolant loops. These coolant loops are distributed throughout the ISS pressurized elements. The primary element coolant loops (i.e., US Laboratory module) contain a fluid accumulator to accommodate thermal expansion of the system. Other element coolant loops are parasitic (i.e., Airlock), have no accumulator, and require an alternative approach to insure that the system Maximum Design Pressure (MDP) is not exceeded during the Launch to Activation phase. During this time the element loop is a stand alone closed individual system. The solution approach for accommodating thermal expansion was affected by interactions of system components and their particular limitations. The mathematical solution approach was challenged by the presence of certain unknown or not readily obtainable physical and thermodynamic characteristics of some system components and processes. The purpose of this paper is to provide a brief description of a few of the solutions that evolved over time, a novel mathematical solution to eliminate some of the unknowns or derive the unknowns experimentally, and the testing and methods undertaken.

Static and Impulsive Models of Solar Active Regions

NASA Technical Reports Server (NTRS)

Patsourakos, S.; Klimchuk, James A.

2008-01-01

The physical modeling of active regions (ARs) and of the global coronal is receiving increasing interest lately. Recent attempts to model ARs using static equilibrium models were quite successful in reproducing AR images of hot soft X-ray (SXR) loops. They however failed to predict the bright EUV warm loops permeating ARs: the synthetic images were dominated by intense footpoint emission. We demonstrate that this failure is due to the very weak dependence of loop temperature on loop length which cannot simultaneously account for both hot and warm loops in the same AR. We then consider time-dependent AR models based on nanoflare heating. We demonstrate that such models can simultaneously reproduce EUV and SXR loops in ARs. Moreover, they predict radial intensity variations consistent with the localized core and extended emissions in SXR and EUV AR observations respectively. We finally show how the AR morphology can be used as a gauge of the properties (duration, energy, spatial dependence, repetition time) of the impulsive heating.

Passive Localization of Underwater Acoustic Beacons

DTIC Science & Technology

1993-09-01

maxtime) TickCounto; aborto ; FSRead(gASerRefln,&numCharln,&addressBuf); TalkSail(’O); iistart the PTR’s data collecticn DrawString(w\\p: H) I display a...34); aborto ; EventLoopO; II main execution loop RAMSDClose(sPortA); HI must close the RAM Drivers before shutdown 193 free(gw); //must release the...kNumExp+l),sizeof(double)); if(wtrue ==NULL) DrawString("\\pCan’t allocate memory for data collection!!! ); aborto ; Nvmeas = calloc(3L*(kStep~kNumExp+l

[Colon volvulus].

PubMed

Monteferrante, E; De Ascentis, G; Mancini, G; Ferranti, F; Rotolo, A; Ciampaglia, F; Gaspari, A L

1995-12-01

The authors report a clinical case and review the international literature. After an analysis of the incidence and the predisposing factors causing this disorder, they focus attention on the question of therapy. In forms with vital loop non-surgical derotation must be attempted. In the event of the failure of non-invasive treatment and to prevent recidivation these forms are treated surgically, also using videolaparoscopy. In forms with non-vital loop, surgery consists of the section of the necrotic segment and preparation of anastomosis which may be immediate or deferred depending on general and local conditions.

The decay of coronal loops brightened by flares and transients

NASA Technical Reports Server (NTRS)

Krieger, A. S.

1978-01-01

Observations of X-ray emitting loops derived from Skylab S-054 photographs, and combined with temperature and brightness estimates from Solrad data, are used to determine brightness decay times resulting from various coronal energy loss mechanisms. Conductive losses are found to be more rapid than radiative losses. Attention is given to the role of geometrical inhibition of conduction as a possible mechanism of brightness decay. Soft X-ray observations are consistent with the continuation of the 'evaporation' driven by thermal conduction late into the decay phase of the event.

Functional Allocation with Airborne Self-Separation Evaluated in a Piloted Simulation

NASA Technical Reports Server (NTRS)

Wing, David J.; Murdoch, Jennifer L.; Chamberlain, James P.; Consiglio, Maria C.; Hoardley, Sherwood T.; Hubbs, Clay E.; Palmer, Michael T.

2010-01-01

A human-in-the-loop simulation experiment was designed and conducted to evaluate an airborne self-separation concept. The activity supports the National Aeronautics and Space Administration s (NASA) research focus on function allocation for separation assurance. The objectives of the experiment were twofold: (1) use experiment design features in common with a companion study of ground-based automated separation assurance to promote comparability, and (2) assess agility of self-separation operations in managing trajectory-changing events in high traffic density, en-route operations with arrival time constraints. This paper describes the experiment and presents initial results associated with subjective workload ratings and group discussion feedback obtained from the experiment s commercial transport pilot participants.

Electronic security device

DOEpatents

Eschbach, E.A.; LeBlanc, E.J.; Griffin, J.W.

1992-03-17

The present invention relates to a security device having a control box containing an electronic system and a communications loop over which the system transmits a signal. The device is constructed so that the communications loop can extend from the control box across the boundary of a portal such as a door into a sealed enclosure into which access is restricted whereby the loop must be damaged or moved in order for an entry to be made into the enclosure. The device is adapted for detecting unauthorized entries into such enclosures such as rooms or containers and for recording the time at which such entries occur for later reference. Additionally, the device detects attempts to tamper or interfere with the operation of the device itself and records the time at which such events take place. In the preferred embodiment, the security device includes a microprocessor-based electronic system and a detection module capable of registering changes in the voltage and phase of the signal transmitted over the loop. 11 figs.

Electronic security device

DOEpatents

Eschbach, Eugene A.; LeBlanc, Edward J.; Griffin, Jeffrey W.

1992-01-01

The present invention relates to a security device having a control box (12) containing an electronic system (50) and a communications loop (14) over which the system transmits a signal. The device is constructed so that the communications loop can extend from the control box across the boundary of a portal such as a door into a sealed enclosure into which access is restricted whereby the loop must be damaged or moved in order for an entry to be made into the enclosure. The device is adapted for detecting unauthorized entries into such enclosures such as rooms or containers and for recording the time at which such entries occur for later reference. Additionally, the device detects attempts to tamper or interfere with the operation of the device itself and records the time at which such events take place. In the preferred embodiment, the security device includes a microprocessor-based electronic system (50) and a detection module (72) capable of registering changes in the voltage and phase of the signal transmitted over the loop.

Higher-order looping and nuclear organization of antigen receptor loci facilitate targeted RAG cleavage and regulated rearrangement in recombination centers

PubMed Central

Chaumeil, Julie; Micsinai, Mariann; Ntziachristos, Panagiotis; Deriano, Ludovic; Wang, Joy M-H; Ji, Yanhong; Nora, Elphege P.; Rodesch, Matthew J.; Jeddeloh, Jeffrey A.; Aifantis, Iannis; Kluger, Yuval; Schatz, David G.; Skok, Jane A.

2013-01-01

SUMMARY V(D)J recombination is essential for generating a diverse array of B and T cell receptors that can recognize and combat foreign antigen. As with any recombination event, tight control is essential to prevent the occurrence of genetic anomalies that drive cellular transformation. One important aspect of regulation is directed targeting of the RAG recombinase. Indeed, RAG accumulates at the 3’ end of individual antigen receptor loci poised for rearrangement, however, it is not known whether focal binding is involved in regulating cleavage, and what mechanisms lead to enrichment of RAG in this region. Here we show that mono-allelic looping out of the 3’ end of Tcra, coupled with transcription and increased chromatin/nuclear accessibility, are linked to focal RAG binding and ATM-mediated regulated mono-allelic cleavage on looped out 3’ regions. Our data identify higher order loop formation as a key determinant of directed RAG targeting and the maintenance of genome stability. PMID:23416051

Markov logic network based complex event detection under uncertainty

NASA Astrophysics Data System (ADS)

Lu, Jingyang; Jia, Bin; Chen, Genshe; Chen, Hua-mei; Sullivan, Nichole; Pham, Khanh; Blasch, Erik

2018-05-01

In a cognitive reasoning system, the four-stage Observe-Orient-Decision-Act (OODA) reasoning loop is of interest. The OODA loop is essential for the situational awareness especially in heterogeneous data fusion. Cognitive reasoning for making decisions can take advantage of different formats of information such as symbolic observations, various real-world sensor readings, or the relationship between intelligent modalities. Markov Logic Network (MLN) provides mathematically sound technique in presenting and fusing data at multiple levels of abstraction, and across multiple intelligent sensors to conduct complex decision-making tasks. In this paper, a scenario about vehicle interaction is investigated, in which uncertainty is taken into consideration as no systematic approaches can perfectly characterize the complex event scenario. MLNs are applied to the terrestrial domain where the dynamic features and relationships among vehicles are captured through multiple sensors and information sources regarding the data uncertainty.

Virtual Sensor Web Architecture

NASA Astrophysics Data System (ADS)

Bose, P.; Zimdars, A.; Hurlburt, N.; Doug, S.

2006-12-01

NASA envisions the development of smart sensor webs, intelligent and integrated observation network that harness distributed sensing assets, their associated continuous and complex data sets, and predictive observation processing mechanisms for timely, collaborative hazard mitigation and enhanced science productivity and reliability. This paper presents Virtual Sensor Web Infrastructure for Collaborative Science (VSICS) Architecture for sustained coordination of (numerical and distributed) model-based processing, closed-loop resource allocation, and observation planning. VSICS's key ideas include i) rich descriptions of sensors as services based on semantic markup languages like OWL and SensorML; ii) service-oriented workflow composition and repair for simple and ensemble models; event-driven workflow execution based on event-based and distributed workflow management mechanisms; and iii) development of autonomous model interaction management capabilities providing closed-loop control of collection resources driven by competing targeted observation needs. We present results from initial work on collaborative science processing involving distributed services (COSEC framework) that is being extended to create VSICS.

Development of a novel multi-layer MRE isolator for suppression of building vibrations under seismic events

NASA Astrophysics Data System (ADS)

Yang, Jian; Sun, Shuaishuai; Tian, Tongfei; Li, Weihua; Du, Haiping; Alici, Gursel; Nakano, Masami

2016-03-01

Protecting civil engineering structures from uncontrollable events such as earthquakes while maintaining their structural integrity and serviceability is very important; this paper describes the performance of a stiffness softening magnetorheological elastomer (MRE) isolator in a scaled three storey building. In order to construct a closed-loop system, a scaled three storey building was designed and built according to the scaling laws, and then four MRE isolator prototypes were fabricated and utilised to isolate the building from the motion induced by a scaled El Centro earthquake. Fuzzy logic was used to output the current signals to the isolators, based on the real-time responses of the building floors, and then a simulation was used to evaluate the feasibility of this closed loop control system before carrying out an experimental test. The simulation and experimental results showed that the stiffness softening MRE isolator controlled by fuzzy logic could suppress structural vibration well.

Polarization switching in undoped and La-doped TlInS2 ferroelectric-semiconductors

NASA Astrophysics Data System (ADS)

Seyidov, MirHasan Yu.; Mikailzade, Faik A.; Suleymanov, Rauf A.; Aliyeva, Vafa B.; Mammadov, Tofig G.; Sharifov, Galib M.

2017-12-01

Dielectric hysteresis loops of pure and lanthanum doped TlInS2 ferroelectric-semiconductors were studied at the frequency 50 Hz for different temperatures below the Curie temperature (Tc). It has been revealed that, without any poling procedure, pure TlInS2 exhibits normal single hysteresis loops at T < Tc. After electric field-cooled treatment of TlInS2 the shape of hysteresis loops was strongly affected by corresponding charged deep level defects which were previously activated during the poling process. As a result, an additional defect polarization state from space charges accumulated on the intrinsic deep level defects has been revealed in pure TlInS2 at the temperatures below Tc. Besides, unusual multiple hysteresis loops were observed in La doped TlInS2 at T < Tc after application of different external perturbations (electric field, exposition and memory effect) to the sample. Measurements of the hysteresis loops in TlInS2:La revealed the slim single, double and even triple polarization-electric field (P-E) hysteresis loops. This intriguing phenomenon is attributed to the domain pinning by photo- and electrically active La-impurity centers. The temperature variation of double-hysteresis loop was also investigated. Due to the heat elimination of the random local defect polar moments, the double-hysteresis loops were transformed into a normal single hysteresis loops on increasing the temperature.

EUV Waves Driven by the Sudden Expansion of Transequatorial Loops Caused by Coronal Jets

NASA Astrophysics Data System (ADS)

Shen, Yuandeng; Tang, Zehao; Miao, Yuhu; Su, Jiangtao; Liu, Yu

2018-06-01

We present two events to study the driving mechanism of extreme-ultraviolet (EUV) waves that are not associated with coronal mass ejections (CMEs), by using high-resolution observations taken by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. Observational results indicate that the observed EUV waves were accompanied by flares and coronal jets, but not the CMEs that were regarded as drivers of most EUV waves in previous studies. In the first case, it is observed that a coronal jet is ejected along a transequatorial loop system at a plane-of-the-sky (POS) speed of 335 ± 22 km s{}-1; in the meantime, an arc-shaped EUV wave appeared on the eastern side of the loop system. In addition, the EUV wave further interacted with another interconnecting loop system and launched a fast propagating (QFP) magnetosonic wave along the loop system, which had a period of 200 s and a speed of 388 ± 65 km s{}-1, respectively. In the second case, we observed a coronal jet that ejected at a POS speed of 282 ± 44 km s{}-1 along a transequatorial loop system as well as the generation of bright EUV waves on the eastern side of the loop system. Based on the observational results, we propose that the observed EUV waves on the eastern side of the transequatorial loop systems are fast-mode magnetosonic waves and that they are driven by the sudden lateral expansion of the transequatorial loop systems due to the direct impingement of the associated coronal jets, while the QFP wave in the fist case formed due to the dispersive evolution of the disturbance caused by the interaction between the EUV wave and the interconnecting coronal loops. It is noted that EUV waves driven by sudden loop expansions have shorter lifetimes than those driven by CMEs.

Multi-thermal observations of the 2010 October 16 flare:heating of a ribbon via loops, or a blast wave?

NASA Astrophysics Data System (ADS)

Christe, Steven; Inglis, A.; Aschwanden, M.; Dennis, B.

2011-05-01

On 2010 October 16th SDO/AIA observed its first flare using automatic exposure control. Coincidentally, this flare also exhibited a large number of interesting features. Firstly, a large ribbon significantly to the solar west of the flare kernel was ignited and was visible in all AIA wavelengths, posing the question as to how this energy was deposited and how it relates to the main flare site. A faint blast wave also emanates from the flare kernel, visible in AIA and observed traveling to the solar west at an estimated speed of 1000 km/s. This blast wave is associated with a weak white-light CME observed with STEREO B and a Type II radio burst observed from Green Bank Observatory (GBSRBS). One possibility is that this blast wave is responsible for the heating of the ribbon. However, closer scrutiny reveals that the flare site and the ribbon are in fact connected magnetically via coronal loops which are heated during the main energy release. These loops are distinct from the expected hot, post-flare loops present within the main flare kernel. RHESSI spectra indicate that these loops are heated to approximately 10 MK in the immediate flare aftermath. Using the multi-temperature capabilities of AIA in combination with RHESSI, and by employing the cross-correlation mapping technique, we are able to measure the loop temperatures as a function of time over several post-flare hours and hence measure the loop cooling rate. We find that the time delay between the appearance of loops in the hottest channel, 131 A, and the cool 171 A channel, is 70 minutes. Yet the causality of this event remains unclear. Is the ribbon heated via these interconnected loops or via a blast wave?

Long-period Intensity Pulsations in Coronal Loops Explained by Thermal Non-equilibrium Cycles

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

Froment, C.; Auchère, F.; Bocchialini, K.

In solar coronal loops, thermal non-equilibrium (TNE) is a phenomenon that can occur when the heating is both highly stratified and quasi-constant. Unambiguous observational identification of TNE would thus permit us to strongly constrain heating scenarios. While TNE is currently the standard interpretation of coronal rain, the long-term periodic evolution predicted by simulations has never been observed. However, the detection of long-period intensity pulsations (periods of several hours) has been recently reported with the Solar and Heliospheric Observatory /EIT, and this phenomenon appears to be very common in loops. Moreover, the three intensity-pulsation events that we recently studied with themore » Solar Dynamics Observatory /Atmospheric Imaging Assembly (AIA) show strong evidence for TNE in warm loops. In this paper, a realistic loop geometry from linear force-free field (LFFF) extrapolations is used as input to 1D hydrodynamic simulations. Our simulations show that, for the present loop geometry, the heating has to be asymmetrical to produce TNE. We analyze in detail one particular simulation that reproduces the average thermal behavior of one of the pulsating loop bundle observed with AIA. We compare the properties of this simulation with those deduced from the observations. The magnetic topology of the LFFF extrapolations points to the presence of sites of preferred reconnection at one footpoint, supporting the presence of asymmetric heating. In addition, we can reproduce the temporal large-scale intensity properties of the pulsating loops. This simulation further strengthens the interpretation of the observed pulsations as signatures of TNE. This consequently provides important information on the heating localization and timescale for these loops.« less

3D-Stereoscopic Analysis of Solar Active Region Loops. 2; SoHo/EIT Observations at Temperatures of 1.5-2.5 MK

NASA Technical Reports Server (NTRS)

Aschwanden, Markus J.; Alexander, David; Hurlburt, Neal; Newmark, Jeffrey S.; Neupert, Werner M.; Klimchuk, J. A.; Gary, G. Allen

1999-01-01

In this paper we study the three-dimensional (3D) structure of hot (T(sub e) approximately equals 1.5 - 2.5 MK) loops in solar active region NOAA 7986, observed on 1996 August 30 with the Extreme-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SoHO). This complements a first study on cooler (T(sub e) approximately equals 1.0 - 1.5 MK) loops of the same active region, using the same method of Dynamic Stereoscopy to reconstruct the 3D geometry. We reconstruct the 3D-coordinates x(s), y(s), z(s), the density n(sub e)(s), and temperature profile T(sub e)(s) of 35 individual loop segments (as function of the loop coordinate s) using EIT 195 A and 284 A images. The major findings are: (1) All loops are found to be in hydrostatic equilibrium, in the entire temperature regime of T(sub e) = 1.0 - 2.5 MK; (2) The analyzed loops have a height of 2-3 scale heights, and thus only segments extending over about one vertical scale height have sufficient emission measure contrast for detection; (3) The temperature gradient over the lowest scale height is of order dT/ds is approximately 1 - 4 K/km; (4) The radiative loss rate is found to exceed the conductive loss rate by about two orders or magnitude, making thermal conduction negligible to explain the temperature structure of the loops; (5) A steady-state can only be achieved when the heating rate E(sub H) matches the radiative loss rate in hydrostatic equilibrium, requiring a heat deposition length lambda(sub H) of the half density scale height lambda, predicting a scaling law with the loop base pressure, EH varies as p(sub 0 exp 2). This favors coronal heating mechanisms that operate near the loop footpoints; (6) We find a reciprocal correlation between the loop pressure p(sub 0) and loop length L, i.e. p(sub 0) varies as 1/L, implying a scaling law of the steady-state requirement with loop length, i.e. E(sub H ) varies as 1/L(exp 2). The heating rate shows no correlation with the loop-aligned magnetic field component B(sub z) at the footpoints, but is correlated with the azimuthal field B(sub phi) = Bz(RDelta Phi/L) of a twisted loop, and is thus consistent with heating mechanisms based on field-aligned currents.

A novel actin binding site of myosin required for effective muscle contraction.

PubMed

Várkuti, Boglárka H; Yang, Zhenhui; Kintses, Bálint; Erdélyi, Péter; Bárdos-Nagy, Irén; Kovács, Attila L; Hári, Péter; Kellermayer, Miklós; Vellai, Tibor; Málnási-Csizmadia, András

2012-02-12

F-actin serves as a track for myosin's motor functions and activates its ATPase activity by several orders of magnitude, enabling actomyosin to produce effective force against load. Although actin activation is a ubiquitous property of all myosin isoforms, the molecular mechanism and physiological role of this activation are unclear. Here we describe a conserved actin-binding region of myosin named the 'activation loop', which interacts with the N-terminal segment of actin. We demonstrate by biochemical, biophysical and in vivo approaches using transgenic Caenorhabditis elegans strains that the interaction between the activation loop and actin accelerates the movement of the relay, stimulating myosin's ATPase activity. This interaction results in efficient force generation, but it is not essential for the unloaded motility. We conclude that the binding of actin to myosin's activation loop specifically increases the ratio of mechanically productive to futile myosin heads, leading to efficient muscle contraction.

Predicted high-water elevations for selected flood events at the Albert Pike Recreation Area, Ouachita National Forest

Treesearch

D.A. Marion

2012-01-01

The hydraulic characteristics are determined for the June 11, 2010, flood on the Little Missouri River at the Albert Pike Recreation Area in Arkansas. These characteristics are then used to predict the high-water elevations for the 10-, 25-, 50-, and 100-year flood events in the Loop B, C, and D Campgrounds of the recreation area. The peak discharge and related...

A double-headed cathepsin B inhibitor devoid of warhead

PubMed Central

Schenker, Patricia; Alfarano, Pietro; Kolb, Peter; Caflisch, Amedeo; Baici, Antonio

2008-01-01

Most synthetic inhibitors of peptidases have been targeted to the active site for inhibiting catalysis through reversible competition with the substrate or by covalent modification of catalytic groups. Cathepsin B is unique among the cysteine peptidase for the presence of a flexible segment, known as the occluding loop, which can block the primed subsites of the substrate binding cleft. With the occluding loop in the open conformation cathepsin B acts as an endopeptidase, and it acts as an exopeptidase when the loop is closed. We have targeted the occluding loop of human cathepsin B at its surface, outside the catalytic center, using a high-throughput docking procedure. The aim was to identify inhibitors that would interact with the occluding loop thereby modulating enzyme activity without the help of chemical warheads against catalytic residues. From a large library of compounds, the in silico approach identified [2-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethylamino]-2-oxoethyl] 2-(furan-2-carbonylamino) acetate, which fulfills the working hypothesis. This molecule possesses two distinct binding moieties and behaves as a reversible, double-headed competitive inhibitor of cathepsin B by excluding synthetic and protein substrates from the active center. The kinetic mechanism of inhibition suggests that the occluding loop is stabilized in its closed conformation, mainly by hydrogen bonds with the inhibitor, thus decreasing endoproteolytic activity of the enzyme. Furthermore, the dioxothiazolidine head of the compound sterically hinders binding of the C-terminal residue of substrates resulting in inhibition of the exopeptidase activity of cathepsin B in a physiopathologically relevant pH range. PMID:18796695

Investigating the Impact of Off-Nominal Events on High-Density "Green" Arrivals

NASA Technical Reports Server (NTRS)

Callatine, Todd J.; Cabrall, Christopher; Kupfer, Michael; Martin, Lynne; Mercer, Joey; Palmer, Everett A.

2012-01-01

Trajectory-based controller tools developed to support a schedule-based terminal-area air traffic management (ATM) concept have been shown effective for enabling green arrivals along Area Navigation (RNAV) routes in moderately high-density traffic conditions. A recent human-in-the-loop simulation investigated the robustness of the concept and tools to off-nominal events events that lead to situations in which runway arrival schedules require adjustments and controllers can no longer use speed control alone to impose the necessary delays. Study participants included a terminal-area Traffic Management Supervisor responsible for adjusting the schedules. Sector-controller participants could issue alternate RNAV transition routes to absorb large delays. The study also included real-time winds/wind-forecast changes. The results indicate that arrival spacing accuracy, schedule conformance, and tool usage and usefulness are similar to that observed in simulations of nominal operations. However, the time and effort required to recover from an off-nominal event is highly context-sensitive, and impacted by the required schedule adjustments and control methods available for managing the evolving situation. The research suggests ways to bolster the off-nominal recovery process, and highlights challenges related to using human-in-the-loop simulation to investigate the safety and robustness of advanced ATM concepts.

Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

PubMed Central

Sarmah, Swapnalee; Marrs, James A.

2014-01-01

BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

A novel seizure detection algorithm informed by hidden Markov model event states

NASA Astrophysics Data System (ADS)

Baldassano, Steven; Wulsin, Drausin; Ung, Hoameng; Blevins, Tyler; Brown, Mesha-Gay; Fox, Emily; Litt, Brian

2016-06-01

Objective. Recently the FDA approved the first responsive, closed-loop intracranial device to treat epilepsy. Because these devices must respond within seconds of seizure onset and not miss events, they are tuned to have high sensitivity, leading to frequent false positive stimulations and decreased battery life. In this work, we propose a more robust seizure detection model. Approach. We use a Bayesian nonparametric Markov switching process to parse intracranial EEG (iEEG) data into distinct dynamic event states. Each event state is then modeled as a multidimensional Gaussian distribution to allow for predictive state assignment. By detecting event states highly specific for seizure onset zones, the method can identify precise regions of iEEG data associated with the transition to seizure activity, reducing false positive detections associated with interictal bursts. The seizure detection algorithm was translated to a real-time application and validated in a small pilot study using 391 days of continuous iEEG data from two dogs with naturally occurring, multifocal epilepsy. A feature-based seizure detector modeled after the NeuroPace RNS System was developed as a control. Main results. Our novel seizure detection method demonstrated an improvement in false negative rate (0/55 seizures missed versus 2/55 seizures missed) as well as a significantly reduced false positive rate (0.0012 h versus 0.058 h-1). All seizures were detected an average of 12.1 ± 6.9 s before the onset of unequivocal epileptic activity (unequivocal epileptic onset (UEO)). Significance. This algorithm represents a computationally inexpensive, individualized, real-time detection method suitable for implantable antiepileptic devices that may considerably reduce false positive rate relative to current industry standards.

Simultaneous Activation of Multiple Memory Systems during Learning: Insights from Electrophysiology and Modeling

DTIC Science & Technology

2010-06-01

autonomic and pain functions, and facilitating/inhibiting voluntary movements. The external segment of the globus pallidus (globus pallidus externa, GPe...or less responsive to pain stimuli. 1.2.4. Other cortico-basal ganglia loops Alexander, Strick and colleagues have additionally defined a number of... orofacial loop and loops through inferotemporal and posterior parietal cortical areas have also been defined. 1.2.5. Interactions between loops Once

Determination of the force systems produced by different configurations of tear drop orthodontic loops.

PubMed

Thiesen, Guilherme; Shimizu, Roberto Hideo; do Valle, Caio Vinicius Martins; do Valle-Corotti, Karyna Martins; Pereira, Jefferson Ricardo; Conti, Paulo Cesar Rodrigues

2013-03-15

To determine the mechanical characteristics of teardrop loop with and without helix fabricated using different metal alloy compositions (stainless steel and beta-titanium), submitted to different intensities of bends preactivation (0° and 40°), and with different cross-sectional dimension of the wire used to build these loops (0.017 x 0.025-in and 0.019 x 0.025-in). Eighty loops used to close spaces were submitted to mechanical tests. The magnitudes of horizontal force, the moment/force ratio, and the load/deflection ratio produced by the specimens were quantified. Loops were submitted to a total activation of 5.0 mm and the values were registered for each 1.0 mm of activation. For statistic data analysis, a analysis of variance was performed and a Tukey's Multiple Comparison test was used as supplement, considering a 5% level of significance. In general, teardrop loops with helix produced lower magnitudes of horizontal force and load/deflection ratio, and higher moment/force ratio than teardrop loops without helix. Among all analyzed variables, metal alloy composition presented greater influence in the horizontal force and in the load/deflection ratio. The moment/force ratio showed to be more influenced by the preactivation of loops for space closure.

Mitotic chromosome compaction via active loop extrusion

NASA Astrophysics Data System (ADS)

Goloborodko, Anton; Imakaev, Maxim; Marko, John; Mirny, Leonid; MIT-Northwestern Team

During cell division, two copies of each chromosome are segregated from each other and compacted more than hundred-fold into the canonical X-shaped structures. According to earlier microscopic observations and the recent Hi-C study, chromosomes are compacted into arrays of consecutive loops of ~100 kilobases. Mechanisms that lead to formation of such loop arrays are largely unknown. Here we propose that, during cell division, chromosomes can be compacted by enzymes that extrude loops on chromatin fibers. First, we use computer simulations and analytical modeling to show that a system of loop-extruding enzymes on a chromatin fiber self-organizes into an array of consecutive dynamic loops. Second, we model the process of loop extrusion in 3D and show that, coupled with the topo II strand-passing activity, it leads to robust compaction and segregation of sister chromatids. This mechanism of chromosomal condensation and segregation does not require additional proteins or specific DNA markup and is robust against variations in the number and properties of such loop extruding enzymes. Work at NU was supported by the NSF through Grants DMR-1206868 and MCB-1022117, and by the NIH through Grants GM105847 and CA193419. Work at MIT was supported by the NIH through Grants GM114190 R01HG003143.

Measuring the magnetic field of a trans-equatorial loop system using coronal seismology

NASA Astrophysics Data System (ADS)

Long, D. M.; Valori, G.; Pérez-Suárez, D.; Morton, R. J.; Vásquez, A. M.

2017-07-01

Context. EIT waves are freely-propagating global pulses in the low corona which are strongly associated with the initial evolution of coronal mass ejections (CMEs). They are thought to be large-amplitude, fast-mode magnetohydrodynamic waves initially driven by the rapid expansion of a CME in the low corona. Aims: An EIT wave was observed on 6 July 2012 to impact an adjacent trans-equatorial loop system which then exhibited a decaying oscillation as it returned to rest. Observations of the loop oscillations were used to estimate the magnetic field strength of the loop system by studying the decaying oscillation of the loop, measuring the propagation of ubiquitous transverse waves in the loop and extrapolating the magnetic field from observed magnetograms. Methods: Observations from the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory (SDO/AIA) and the Coronal Multi-channel Polarimeter (CoMP) were used to study the event. An Empirical Mode Decomposition analysis was used to characterise the oscillation of the loop system in CoMP Doppler velocity and line width and in AIA intensity. Results: The loop system was shown to oscillate in the 2nd harmonic mode rather than at the fundamental frequency, with the seismological analysis returning an estimated magnetic field strength of ≈ 5.5 ± 1.5 G. This compares to the magnetic field strength estimates of ≈1-9 G and ≈3-9 G found using the measurements of transverse wave propagation and magnetic field extrapolation respectively. A movie associated to Figs. 1 and 2 is available at http://www.aanda.org

Kinetics of interior loop formation in semiflexible chains.

PubMed

Hyeon, Changbong; Thirumalai, D

2006-03-14

Loop formation between monomers in the interior of semiflexible chains describes elementary events in biomolecular folding and DNA bending. We calculate analytically the interior distance distribution function for semiflexible chains using a mean field approach. Using the potential of mean force derived from the distance distribution function we present a simple expression for the kinetics of interior looping by adopting Kramers theory. For the parameters, that are appropriate for DNA, the theoretical predictions in comparison with the case are in excellent agreement with explicit Brownian dynamics simulations of wormlike chain (WLC) model. The interior looping times (tauIC) can be greatly altered in the cases when the stiffness of the loop differs from that of the dangling ends. If the dangling end is stiffer than the loop then tauIC increases for the case of the WLC with uniform persistence length. In contrast, attachment of flexible dangling ends enhances rate of interior loop formation. The theory also shows that if the monomers are charged and interact via screened Coulomb potential then both the cyclization (tauc) and interior looping (tauIC) times greatly increase at low ionic concentration. Because both tauc and tauIC are determined essentially by the effective persistence length [lp(R)] we computed lp(R) by varying the range of the repulsive interaction between the monomers. For short range interactions lp(R) nearly coincides with the bare persistence length which is determined largely by the backbone chain connectivity. This finding rationalizes the efficacy of describing a number of experimental observations (response of biopolymers to force and cyclization kinetics) in biomolecules using WLC model with an effective persistence length.

An investigation of coronal active region loop structures using AS&E rocket X-ray images

NASA Technical Reports Server (NTRS)

Webb, D. F.

1983-01-01

Simultaneous high spatial resolution observations at 6 cm in soft X-rays, in photospheric magnetograms, and in optical filtergrams were used to compare the most intense sources of centimetric emission in two active regions to coronal loops, sunspots, chromospheric structures, and photospheric magnetic fields. Results show that the majority of the bright microwave components are not associated with sunspots or X-ray emission. A nonthermal mechanism appears necessary to explain the brightest microwave components, discrete regions of continuous particle acceleration may be common in active regions. Studies of the plasma parameters of selected loops imply that the radio emission is consistent with gyro-resonance absorption at the third and fourth harmonic, at least from part of each loop. Results are presented for: (1) X-ray and microwave observations of active regions; (2) comparison of coronal holes observed in soft X-rays and Hel 10830 A spectrosheliograms; and (3) the reappearance of polar coronal holes and the evolution of the solar magnetic field.

A mobile loop near the active site acts as a switch between the dual activities of a viral protease/deubiquitinase

PubMed Central

Ayach, Maya; Fieulaine, Sonia

2017-01-01

The positive-strand RNA virus Turnip yellow mosaic virus (TYMV) encodes an ovarian tumor (OTU)-like protease/deubiquitinase (PRO/DUB) protein domain involved both in proteolytic processing of the viral polyprotein through its PRO activity, and in removal of ubiquitin chains from ubiquitylated substrates through its DUB activity. Here, the crystal structures of TYMV PRO/DUB mutants and molecular dynamics simulations reveal that an idiosyncratic mobile loop participates in reversibly constricting its unusual catalytic site by adopting "open", "intermediate" or "closed" conformations. The two cis-prolines of the loop form a rigid flap that in the most closed conformation zips up against the other side of the catalytic cleft. The intermediate and closed conformations also correlate with a reordering of the TYMV PRO/DUB catalytic dyad, that then assumes a classical, yet still unusually mobile, OTU DUB alignment. Further structure-based mutants designed to interfere with the loop's mobility were assessed for enzymatic activity in vitro and in vivo, and were shown to display reduced DUB activity while retaining PRO activity. This indicates that control of the switching between the dual PRO/DUB activities resides prominently within this loop next to the active site. Introduction of mutations into the viral genome revealed that the DUB activity contributes to the extent of viral RNA accumulation both in single cells and in whole plants. In addition, the conformation of the mobile flap was also found to influence symptoms severity in planta. Such mutants now provide powerful tools with which to study the specific roles of reversible ubiquitylation in viral infection. PMID:29117247

Comparison between two models of energy balance in coronal loops

NASA Astrophysics Data System (ADS)

Mac Cormack, C.; López Fuentes, M.; Vásquez, A. M.; Nuevo, F. A.; Frazin, R. A.; Landi, E.

2017-10-01

In this work we compare two models to analyze the energy balance along coronal magnetic loops. For the first stationary model we deduce an expression of the energy balance along the loops expressed in terms of quantities provided by the combination of differential emission measure tomography (DEMT) applied to EUV images time series and potential extrapolations of the coronal magnetic field. The second applied model is a 0D hydrodynamic model that provides the evolution of the average properties of the coronal plasma along the loops, using as input parameters the loop length and the heating rate obtained with the first model. We compare the models for two Carrington rotations (CR) corresponding to different periods of activity: CR 2081, corresponding to a period of minimum activity observed with the Extreme Ultraviolet Imager (EUVI) on board of the Solar Terrestrial Relations Observatory (STEREO), and CR 2099, corresponding to a period of activity increase observed with the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory (SDO). The results of the models are consistent for both rotations.

A dual-loop model of the human controller

NASA Technical Reports Server (NTRS)

Hess, R. A.

1977-01-01

A representative model of the human controller in single-axis compensatory tracking tasks that exhibits an internal feedback loop which is not evident in single-loop models now in common use is presented. This hypothetical inner-loop involves a neuromuscular command signal derived from the time rate of change of controlled element output which is due to control activity. It is not contended that the single-loop human controller models now in use are incorrect, but that they contain an implicit but important internal loop closure, which, if explicitly considered, can account for a good deal of the adaptive nature of the human controller in a systematic manner.

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.

PubMed

Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

2016-01-01

Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.

Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics.

PubMed

Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E

2013-06-01

To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

And the Human Saves the Day or Maybe They Ruin It, The Importance of Humans in the Loop

NASA Technical Reports Server (NTRS)

DeMott, Diana L.; Boyer, Roger L.

2017-01-01

Flying a mission in space requires a massive commitment of resources, and without the talent and commitment of the people involved in this effort we would never leave the atmosphere of Earth as safely as we have. When we use the phrase "humans in the loop", it could apply to almost any endeavor since everything starts with humans developing a concept, completing the design process, building or implementing a product and using the product to achieve a goal or purpose. Narrowing the focus to spaceflight, there are a variety of individuals involved throughout the preparations for flight and the flight itself. All of the humans involved add value and support for program success. The paper discusses the concepts of human involvement in technological programs, how a Probabilistic Risk Assessment (PRA) accounts for the human in the loop for potential missions using a technique called Human Reliability Analysis (HRA) and the tradeoffs between having a human in the loop or not. Human actions can increase or decrease the overall risk via initiating events or mitigating them, thus removing the human from the loop doesn't always lowers the risk.

Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains

PubMed Central

Daidone, Isabella; Neuweiler, Hannes; Doose, Sören; Sauer, Markus; Smith, Jeremy C.

2010-01-01

Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20–100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient β-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events. PMID:20098498

Activating clinical trials: a process improvement approach.

PubMed

Martinez, Diego A; Tsalatsanis, Athanasios; Yalcin, Ali; Zayas-Castro, José L; Djulbegovic, Benjamin

2016-02-24

The administrative process associated with clinical trial activation has been criticized as costly, complex, and time-consuming. Prior research has concentrated on identifying administrative barriers and proposing various solutions to reduce activation time, and consequently associated costs. Here, we expand on previous research by incorporating social network analysis and discrete-event simulation to support process improvement decision-making. We searched for all operational data associated with the administrative process of activating industry-sponsored clinical trials at the Office of Clinical Research of the University of South Florida in Tampa, Florida. We limited the search to those trials initiated and activated between July 2011 and June 2012. We described the process using value stream mapping, studied the interactions of the various process participants using social network analysis, and modeled potential process modifications using discrete-event simulation. The administrative process comprised 5 sub-processes, 30 activities, 11 decision points, 5 loops, and 8 participants. The mean activation time was 76.6 days. Rate-limiting sub-processes were those of contract and budget development. Key participants during contract and budget development were the Office of Clinical Research, sponsors, and the principal investigator. Simulation results indicate that slight increments on the number of trials, arriving to the Office of Clinical Research, would increase activation time by 11 %. Also, incrementing the efficiency of contract and budget development would reduce the activation time by 28 %. Finally, better synchronization between contract and budget development would reduce time spent on batching documentation; however, no improvements would be attained in total activation time. The presented process improvement analytic framework not only identifies administrative barriers, but also helps to devise and evaluate potential improvement scenarios. The strength of our framework lies in its system analysis approach that recognizes the stochastic duration of the activation process and the interdependence between process activities and entities.

Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism.

PubMed

Fasching, Clare L; Cejka, Petr; Kowalczykowski, Stephen C; Heyer, Wolf-Dietrich

2015-02-19

The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops. Copyright © 2015 Elsevier Inc. All rights reserved.

Partial deletion of beta9 loop in pancreatic lipase-related protein 2 reduces enzyme activity with a larger effect on long acyl chain substrates.

PubMed

Dridi, Kaouthar; Amara, Sawsan; Bezzine, Sofiane; Rodriguez, Jorge A; Carrière, Frédéric; Gaussier, Hélène

2013-07-01

Structural studies on pancreatic lipase have revealed a complex architecture of surface loops surrounding the enzyme active site and potentially involved in interactions with lipids. Two of them, the lid and beta loop, expose a large hydrophobic surface and are considered as acyl chain binding sites based on their interaction with an alkyl phosphonate inhibitor. While the role of the lid in substrate recognition and selectivity has been extensively studied, the implication of beta9 loop in acyl chain stabilization remained hypothetical. The characterization of an enzyme with a natural deletion of the lid, guinea pig pancreatic lipase-related protein 2 (GPLRP2), suggests however an essential contribution of the beta9 loop in the stabilization of the acyl enzyme intermediate formed during the lipolysis reaction. A GPLRP2 mutant with a seven-residue deletion of beta9 loop (GPLRP2-deltabeta9) was produced and its enzyme activity was measured using various substrates (triglycerides, monoglycerides, galactolipids, phospholipids, vinyl esters) with short, medium and long acyl chains. Whatever the substrate tested, GPLRP2-deltabeta9 activity is drastically reduced compared to that of wild-type GPLRP2 and this effect is more pronounced as the length of substrate acyl chain increases. Changes in relative substrate selectivity and stereoselectivity remained however weak. The deletion within beta9 loop has also a negative effect on the rate of enzyme inhibition by alkyl phosphonates. All these findings indicate that the reduced enzyme turnover observed with GPLRP2-deltabeta9 results from a weaker stabilization of the acyl enzyme intermediate due to a loss of hydrophobic interactions.

Folding of the natural hammerhead ribozyme is enhanced by interaction of auxiliary elements

PubMed Central

PENEDO, J. CARLOS; WILSON, TIMOTHY J.; JAYASENA, SUMEDHA D.; KHVOROVA, ANASTASIA; LILLEY, DAVID M.J.

2004-01-01

It has been shown that the activity of the hammerhead ribozyme at μM magnesium ion concentrations is markedly increased by the inclusion of loops in helices I and II. We have studied the effect of such loops on the magnesium ion-induced folding of the ribozyme, using fluorescence resonance energy transfer. We find that with the loops in place, folding into the active conformation occurs in a single step, in the μM range of magnesium ion concentration. Disruption of the loop–loop interaction leads to a reversion to two-step folding, with the second stage requiring mM concentrations of magnesium ion. Sodium ions also promote the folding of the natural form of the ribozyme at high concentrations, but the folding occurs as a two-stage process. The loops clearly act as important auxiliary elements in the function of the ribozyme, permitting folding to occur efficiently under physiological conditions. PMID:15100442

Coupling between Catalytic Loop Motions and Enzyme Global Dynamics

PubMed Central

Kurkcuoglu, Zeynep; Bakan, Ahmet; Kocaman, Duygu; Bahar, Ivet; Doruker, Pemra

2012-01-01

Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops. Our dataset includes a total of 117 crystal structures for ten enzymes of different sizes and oligomerization states. Each enzyme contains a specific functional/catalytic loop (10–21 residues long) that closes over the active site during catalysis. Principal component analysis (PCA) of the available crystal structures (including apo and ligand-bound forms) for each enzyme revealed the dominant conformational changes taking place in these loops upon substrate binding. These experimentally observed loop reconfigurations are shown to be predominantly driven by energetically favored modes of motion intrinsically accessible to the enzyme in the absence of its substrate. The analysis suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site. PMID:23028297

Retroviruses Hijack Chromatin Loops to Drive Oncogene Expression and Highlight the Chromatin Architecture around Proto-Oncogenic Loci

PubMed Central

Pattison, Jillian M.; Wright, Jason B.; Cole, Michael D.

2015-01-01

The majority of the genome consists of intergenic and non-coding DNA sequences shown to play a major role in different gene regulatory networks. However, the specific potency of these distal elements as well as how these regions exert function across large genomic distances remains unclear. To address these unresolved issues, we closely examined the chromatin architecture around proto-oncogenic loci in the mouse and human genomes to demonstrate a functional role for chromatin looping in distal gene regulation. Using cell culture models, we show that tumorigenic retroviral integration sites within the mouse genome occur near existing large chromatin loops and that this chromatin architecture is maintained within the human genome as well. Significantly, as mutagenesis screens are not feasible in humans, we demonstrate a way to leverage existing screens in mice to identify disease relevant human enhancers and expose novel disease mechanisms. For instance, we characterize the epigenetic landscape upstream of the human Cyclin D1 locus to find multiple distal interactions that contribute to the complex cis-regulation of this cell cycle gene. Furthermore, we characterize a novel distal interaction upstream of the Cyclin D1 gene which provides mechanistic evidence for the abundant overexpression of Cyclin D1 occurring in multiple myeloma cells harboring a pathogenic translocation event. Through use of mapped retroviral integrations and translocation breakpoints, our studies highlight the importance of chromatin looping in oncogene expression, elucidate the epigenetic mechanisms crucial for distal cis-regulation, and in one particular instance, explain how a translocation event drives tumorigenesis through upregulation of a proto-oncogene. PMID:25799187

Open magnetic fields in active regions

NASA Technical Reports Server (NTRS)

Svestka, Z.; Solodyna, C. V.; Howard, R.; Levine, R. H.

1977-01-01

Soft X-ray images and magnetograms of several active regions and coronal holes are examined which support the interpretation that some of the dark X-ray gaps seen between interconnecting loops and inner cores of active regions are foot points of open field lines inside the active regions. Characteristics of the investigated dark gaps are summarized. All the active regions with dark X-ray gaps at the proper place and with the correct polarity predicted by global potential extrapolation of photospheric magnetic fields are shown to be old active regions, indicating that field opening is accomplished only in a late phase of active-region development. It is noted that some of the observed dark gaps probably have nothing in common with open fields, but are either due to the decreased temperature in low-lying portions of interconnecting loops or are the roots of higher and less dense or cooler loops.

A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback

PubMed Central

2018-01-01

During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence of neural fluctuations, across the brain, on closed-loop brain/body/environment interactions strongly supporting the idea that brain function cannot be fully understood through open-loop approaches alone. PMID:29342146

A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

PubMed

Buckley, Christopher L; Toyoizumi, Taro

2018-01-01

During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence of neural fluctuations, across the brain, on closed-loop brain/body/environment interactions strongly supporting the idea that brain function cannot be fully understood through open-loop approaches alone.

Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation.

PubMed

Leandro, João; Stokka, Anne J; Teigen, Knut; Andersen, Ole A; Flatmark, Torgeir

2017-07-01

Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Biochemical and biophysical work has demonstrated that it cycles between two states with a variably low and a high activity, and that the substrate l-Phe is the key player in this transition. X-ray structures of the catalytic domain have shown mobility of a partially intrinsically disordered Tyr 138 -loop to the active site in the presence of l-Phe. The mechanism by which the loop dynamics are coupled to substrate binding at the active site in tetrameric PAH is not fully understood. We have here conducted functional studies of four Tyr 138 point mutants. A high linear correlation ( r 2 = 0.99) was observed between their effects on the catalytic efficiency of the catalytic domain dimers and the corresponding effect on the catalytic efficiency of substrate-activated full-length tetramers. In the tetramers, a correlation ( r 2 = 0.96) was also observed between the increase in catalytic efficiency (activation) and the global conformational change (surface plasmon resonance signal response) at the same l-Phe concentration. The new data support a similar functional importance of the Tyr 138 -loop in the catalytic domain and the full-length enzyme homotetramer.

Determination of air-loop volume and radon partition coefficient for measuring radon in water sample.

PubMed

Lee, Kil Yong; Burnett, William C

A simple method for the direct determination of the air-loop volume in a RAD7 system as well as the radon partition coefficient was developed allowing for an accurate measurement of the radon activity in any type of water. The air-loop volume may be measured directly using an external radon source and an empty bottle with a precisely measured volume. The partition coefficient and activity of radon in the water sample may then be determined via the RAD7 using the determined air-loop volume. Activity ratios instead of absolute activities were used to measure the air-loop volume and the radon partition coefficient. In order to verify this approach, we measured the radon partition coefficient in deionized water in the temperature range of 10-30 °C and compared the values to those calculated from the well-known Weigel equation. The results were within 5 % variance throughout the temperature range. We also applied the approach for measurement of the radon partition coefficient in synthetic saline water (0-75 ppt salinity) as well as tap water. The radon activity of the tap water sample was determined by this method as well as the standard RAD-H 2 O and BigBottle RAD-H 2 O. The results have shown good agreement between this method and the standard methods.

A Redox 2-Cys Mechanism Regulates the Catalytic Activity of Divergent Cyclophilins1[W

PubMed Central

Campos, Bruna Medéia; Sforça, Mauricio Luis; Ambrosio, Andre Luis Berteli; Domingues, Mariane Noronha; Brasil de Souza, Tatiana de Arruda Campos; Barbosa, João Alexandre Ribeiro Gonçalvez; Leme, Adriana Franco Paes; Perez, Carlos Alberto; Whittaker, Sara Britt-Marie; Murakami, Mario Tyago; Zeri, Ana Carolina de Matos; Benedetti, Celso Eduardo

2013-01-01

The citrus (Citrus sinensis) cyclophilin CsCyp is a target of the Xanthomonas citri transcription activator-like effector PthA, required to elicit cankers on citrus. CsCyp binds the citrus thioredoxin CsTdx and the carboxyl-terminal domain of RNA polymerase II and is a divergent cyclophilin that carries the additional loop KSGKPLH, invariable cysteine (Cys) residues Cys-40 and Cys-168, and the conserved glutamate (Glu) Glu-83. Despite the suggested roles in ATP and metal binding, the functions of these unique structural elements remain unknown. Here, we show that the conserved Cys residues form a disulfide bond that inactivates the enzyme, whereas Glu-83, which belongs to the catalytic loop and is also critical for enzyme activity, is anchored to the divergent loop to maintain the active site open. In addition, we demonstrate that Cys-40 and Cys-168 are required for the interaction with CsTdx and that CsCyp binds the citrus carboxyl-terminal domain of RNA polymerase II YSPSAP repeat. Our data support a model where formation of the Cys-40-Cys-168 disulfide bond induces a conformational change that disrupts the interaction of the divergent and catalytic loops, via Glu-83, causing the active site to close. This suggests a new type of allosteric regulation in divergent cyclophilins, involving disulfide bond formation and a loop-displacement mechanism. PMID:23709667

Translation initiation events on structured eukaryotic mRNAs generate gene expression noise

PubMed Central

Dacheux, Estelle; Malys, Naglis; Meng, Xiang; Ramachandran, Vinoy; Mendes, Pedro

2017-01-01

Abstract Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem–loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise. The noise-enhancing effect of the stem–loop structure also remains operational when combined with an upstream open reading frame. This has broad significance, since these elements are known to modulate the expression of a diversity of eukaryotic genes. Our findings suggest a mechanism for posttranscriptional noise generation that will contribute to understanding of the generally poor correlation between protein-level stochasticity and transcriptional bursting. We propose that posttranscriptional stochasticity can be linked to cycles of folding/unfolding of a stem–loop structure, or to interconversion between higher-order structural conformations of a G-rich motif, and have created a correspondingly configured computational model that generates fits to the experimental data. Stochastic events occurring during the ribosomal scanning process can therefore feature alongside transcriptional bursting as a source of noise. PMID:28521011

Conservative Tryptophan Mutants of the Protein Tyrosine Phosphatase YopH Exhibit Impaired WPD-Loop Function and Crystallize with Divanadate Esters in Their Active Sites

PubMed Central

Moise, Gwendolyn; Gallup, Nathan M.; Alexandrova, Anastassia N.; Hengge, Alvan C.; Johnson, Sean J.

2016-01-01

Catalysis in protein tyrosine phosphatases (PTPs) involves movement of a protein loop called the WPD loop that brings a conserved aspartic acid into the active site to function as a general acid. Mutation of the tryptophan in the WPD loop of the PTP YopH to any other residue with a planar, aromatic side chain (phenylalanine, tyrosine, or histidine) disables general acid catalysis. Crystal structures reveal these conservative mutations leave this critical loop in a catalytically unproductive, quasi-open position. Although the loop positions in crystal structures are similar for all three conservative mutants, the reasons inhibiting normal loop closure differ for each mutant. In the W354F and W354Y mutants, steric clashes result from six-membered rings occupying the position of the five-membered ring of the native indole side chain. The histidine mutant dysfunction results from new hydrogen bonds stabilizing the unproductive position. The results demonstrate how even modest modifications can disrupt catalytically important protein dynamics. Crystallization of all the catalytically compromised mutants in the presence of vanadate gave rise to vanadate dimers at the active site. In W354Y and W354H, a divanadate ester with glycerol is observed. Such species have precedence in solution and are known from the small molecule crystal database. Such species have not been observed in the active site of a phosphatase, as a functional phosphatase would rapidly catalyze their decomposition. The compromised functionality of the mutants allows the trapping of species that undoubtedly form in solution and are capable of binding at the active sites of PTPs, and, presumably, other phosphatases. In addition to monomeric vanadate, such higher-order vanadium-based molecules are likely involved in the interaction of vanadate with PTPs in solution. PMID:26445170

NFκB- and AP-1-mediated DNA looping regulates matrix metalloproteinase-9 transcription in TNF-α-treated human leukemia U937 cells.

PubMed

Chen, Ying-Jung; Chang, Long-Sen

2015-10-01

The aim of this study is to explore the spatial association of critical genomic elements in the effect of TNF-α on matrix metalloproteinase-9 (MMP-9) expression in human leukemia U937 cells. TNF-α up-regulated MMP-9 protein expression and mRNA level in U937 cells, and Akt-mediated-NFκB/p65 activation and JNK-mediated c-Jun activation were proven to be involved in TNF-α-induced MMP-9 up-regulation. Promoter luciferase activity assay revealed that NFκB (nt-600) and AP-1 (nt-79) binding sites were crucial for TNF-α-induced transcription of MMP-9 gene. The results of a chromatin immunoprecipitation assay indicated that TNF-α reduced histone deacetylase-1 (HDAC-1) recruitment but increased p300 (a histone acetyltransferase) recruitment to MMP-9 promoter regions surrounding NFκB and AP-1 binding sites. Consistently, TNF-α increased enrichment of the acetylated histone H3 mark on MMP-9 promoter regions. DNA affinity purification assay revealed that p300 and HDAC1 could bind oligonucleotides containing AP-1/c-Jun and NFκB/p65 binding sites. Chromosome conformation capture assay showed that TNF-α stimulated chromosomal loops in the MMP-9 promoter via NFκB/p65 and AP-1/c-Jun. The p300-associated acetyltransferase activity was crucial for p65/c-Jun-mediated DNA looping, and inhibition of HDAC activity increased the level of DNA looping. Reduction in the level of DNA looping eliminated all TNF-α-stimulated MMP-9 up-regulation. Taken together, our data suggest that p65/c-Jun-mediated DNA looping is involved in TNF-α-induced MMP-9 up-regulation and that the recruitment of p300 or HDAC1 to NFκB and AP-1 binding sites modifies the level of DNA looping. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential Ubiquitin Binding by the Acidic Loops of Ube2g1 and Ube2r1 Enzymes Distinguishes Their Lys-48-ubiquitylation Activities*

PubMed Central

Choi, Yun-Seok; Lee, Yun-Ju; Lee, Seo-Yeon; Shi, Lei; Ha, Jung-Hye; Cheong, Hae-Kap; Cheong, Chaejoon; Cohen, Robert E.; Ryu, Kyoung-Seok

2015-01-01

The ubiquitin E2 enzymes, Ube2g1 and Ube2r1, are able to synthesize Lys-48-linked polyubiquitins without an E3 ligase but how that is accomplished has been unclear. Although both E2s contain essential acidic loops, only Ube2r1 requires an additional C-terminal extension (184–196) for efficient Lys-48-ubiquitylation activity. The presence of Tyr-102 and Tyr-104 in the Ube2g1 acidic loop enhanced both ubiquitin binding and Lys-48-ubiquitylation and distinguished Ube2g1 from the otherwise similar truncated Ube2r11–183 (Ube2r1C). Replacement of Gln-105–Ser-106–Gly-107 in the acidic loop of Ube2r1C (Ube2r1CYGY) by the corresponding residues from Ube2g1 (Tyr-102–Gly-103–Tyr-104) increased Lys-48-ubiquitylation activity and ubiquitin binding. Two E2∼UB thioester mimics (oxyester and disulfide) were prepared to characterize the ubiquitin binding activity of the acidic loop. The oxyester but not the disulfide derivative was found to be a functional equivalent of the E2∼UB thioester. The ubiquitin moiety of the Ube2r1CC93S-[15N]UBK48R oxyester displayed two-state conformational exchange, whereas the Ube2r1CC93S/YGY-[15N]UBK48R oxyester showed predominantly one state. Together with NMR studies that compared UBK48R oxyesters of the wild-type and the acidic loop mutant (Y102G/Y104G) forms of Ube2g1, in vitro ubiquitylation assays with various mutation forms of the E2s revealed how the intramolecular interaction between the acidic loop and the attached donor ubiquitin regulates Lys-48-ubiquitylation activity. PMID:25471371

Steady State Model for Solar Coronal Loops

NASA Astrophysics Data System (ADS)

Sugiyama, L.; Asgari-Targhi, M.

2017-12-01

Solar coronal loops on the surface of the sun provide background magnetic and plasma structures for the release of a significant amount of the sun's energy, through energetic solar flares and coronal mass ejections and more gradual processes. Understanding their steady states is the first step in understanding loop dynamics. A consistent MHD steady state model, for a curved magnetic flux rope that contains plasma, has been developed[1] for simple coronal loops with both ends anchored in the photosphere. Plasma pressure or current makes the loop unstable to expansion in major radius and must be balanced by external forces, such as the solar gravity. The MHD momentum equation has a well defined small parameter ordering in the loop inverse aspect ratio ɛ=a/Ro (minor/major radius). Different types of common coronal loops fall in different parameter regimes, determined by the relative values of the plasma beta β=po/(Bo2/2μo), the MHD gravity parameter Ĝ≡ga/vA2 (the gravitational acceleration g normalized to the minor radius a and shear Alfvén velocity vA), and ɛ. The largest possible gravity, Ĝ ɛ1β, corresponds to the largest loops because it reduces the plasma density at the top of the loop exponentially compared to its lower ends, reducing the downward gravitational force -ρĜ there. The thin loops that are ubiquitous in solar active regions have ``high'' beta, β ɛ1, for ɛ≃0.02, and fit the predicted model scalings. The thicker loops that can give rise to flares and CMEs have ``low'' beta, β ɛ2. Cool loops, such as solar filaments outside active regions, that have a central pressure lower than that of the surrounding corona would have the strongest stability against radial expansion. The model raises a number of questions about the connection of loops to the photosphere and the force-free nature of the magnetic field there. [1] L. Sugiyama, M. Asgari-Targhi, Phys. Plasmas 24, 022904 (2017).

3D-Stereoscopic Analysis of Solar Active Region Loops: I: SoHo/EIT Observations at Temperatures of 1.0-1.5 MK

NASA Technical Reports Server (NTRS)

Aschwanden, Markus J.; Newmark, Jeff; Delaboudiniere, Jean-Pierre; Neupert, Werner M.; Portier-Fozzani, Fabrice; Gary, G. Allen; Zucker, Arik

1998-01-01

The three-dimensional (3D) structure of solar active region NOAA 7986 observed on 1996 August 30 with the Extrem-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SoHO) is analyzed. We develop a new method of Dynamic Stereoscopy to reconstruct the 3D geometry of dynamically changing loops, which allows us to determine the orientation of the loop plane with respect to the line-of-sight, a prerequisite to correct properly for projection effects in 3D loop models. With this method and the filter-ratio technique applied to EIT 171 A and 195 A images we determine the 3D coordinates (x(s), y(s), z(s)), the loop width) w(s), the electron density n(sub e)(s), and the electron temperature T(sub e)(s) as function of the loop length s for 30 loop segments. Fitting the loop densities with an exponential density model n(sub e)(h) we find that the so inferred scale height temperatures, T(sub e)(sup lambda) = 1.22 +/- 0.23 MK, match closely the EIT filter-ratio temperatures, T(sub e)(sup FIT) = 1.21 +/- 0.06 MK. We conclude that these rather large-scale loops (with heights of h approx. equals 50 - 200 Mm) that dominate EIT 171 A images are close to thermal equilibrium. Most of the loops show no significant thickness variation w(s), but many exhibit a trend of increasing temperature (dT/ds greater than 0) above the footpoint.

Top3-Rmi1 dissolve Rad51-mediated D-loops by a topoisomerase-based mechanism

PubMed Central

Fasching, Clare L.; Cejka, Petr; Kowalczykowski, Stephen C.; Heyer, Wolf-Dietrich

2015-01-01

Summary The displacement loop (D-loop) is the DNA strand invasion product formed during homologous recombination. Disruption of nascent D-loops represents a mechanism of anti-recombination. During Synthesis-Dependent Strand Annealing D-loop disruption after extension of the invading strand is an integral step of the pathway and ensures a non-crossover outcome. The proteins implicated in D-loop disruption are DNA motor proteins/helicases acting by migrating DNA junctions. Here we report an unanticipated mechanism of D-loop dissolution mediated by DNA topoisomerase 3 (Top3) and dependent on its catalytic activity. D-loop dissolution catalyzed by yeast Top3 is highly specific for yeast Rad51/Rad54-mediated D-loops, whereas protein-free D-loops or D-loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also the human Topoisomerase IIIα-RMI1–RMI2 complex is capable of dissolving D-loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is in part a result of unprocessed D-loops. PMID:25699708

The association of transequatorial loops in the solar corona with coronal mass ejection onset

NASA Astrophysics Data System (ADS)

Glover, A.; Harra, L. K.; Matthews, S. A.; Foley, C. A.

2003-03-01

It has been shown that transequatorial loops can disappear in association with the onset of a coronal mass ejection (CME) (Khan & Hudson \\cite{khan}). We extend this result by considering a larger sample of transequatorial loop systems (TLS) to investigate their associated flaring and CME activity. We find 10 of a total 18 TLS considered here to be associated with flaring and CME onset originating from a connected active region. A total 33 cases of flaring and associated CME onset are observed from these 10 systems during their lifetime. We observe the influence of this activity on the TLS in each case. In contrast to the Khan & Hudson result, we find evidence that transequatorial loop eruption leading to soft X-ray brightening equivalent in temperature to a B-class flare is equally as common as dimming in the corona. Consequently we conclude that the scenario observed by Khan & Hudson is not universal and that other types of CME-TLS association occur. It was found that for transequatorial loops that were associated with CMEs the asymmetry in longitude was larger than for those that were not associated to a CME by 10o. In addition, the extent in latitude (as a measure of the loop length) was nearly twice as large for those TLS associated with CMEs than those that were not. The asymmetry in latitude was actually on average larger for those TLS not associated with CMEs, than for those that were. This suggests that differential rotation is not a major contributor to the production of CMEs from transequatorial loops. Instead it is more likely for a CME to be produced if the loop is long, and if there is a large asymmetry in longitude. The implications of these results for CME onset prediction are discussed.

The Minimum M3-M4 Loop Length of Neurotransmitter-activated Pentameric Receptors Is Critical for the Structural Integrity of Cytoplasmic Portals*

PubMed Central

Baptista-Hon, Daniel T.; Deeb, Tarek Z.; Lambert, Jeremy J.; Peters, John A.; Hales, Tim G.

2013-01-01

The 5-HT3A receptor homology model, based on the partial structure of the nicotinic acetylcholine receptor from Torpedo marmorata, reveals an asymmetric ion channel with five portals framed by adjacent helical amphipathic (HA) stretches within the 114-residue loop between the M3 and M4 membrane-spanning domains. The positive charge of Arg-436, located within the HA stretch, is a rate-limiting determinant of single channel conductance (γ). Further analysis reveals that positive charge and volume of residue 436 are determinants of 5-HT3A receptor inward rectification, exposing an additional role for portals. A structurally unresolved stretch of 85 residues constitutes the bulk of the M3-M4 loop, leaving a >45-Å gap in the model between M3 and the HA stretch. There are no additional structural data for this loop, which is vestigial in bacterial pentameric ligand-gated ion channels and was largely removed for crystallization of the Caenorhabditis elegans glutamate-activated pentameric ligand-gated ion channels. We created 5-HT3A subunit loop truncation mutants, in which sequences framing the putative portals were retained, to determine the minimum number of residues required to maintain their functional integrity. Truncation to between 90 and 75 amino acids produced 5-HT3A receptors with unaltered rectification. Truncation to 70 residues abolished rectification and increased γ. These findings reveal a critical M3-M4 loop length required for functions attributable to cytoplasmic portals. Examination of all 44 subunits of the human neurotransmitter-activated Cys-loop receptors reveals that, despite considerable variability in their sequences and lengths, all M3-M4 loops exceed 70 residues, suggesting a fundamental requirement for portal integrity. PMID:23740249

Dual allosteric activation mechanisms in monomeric human glucokinase

PubMed Central

Whittington, A. Carl; Larion, Mioara; Bowler, Joseph M.; Ramsey, Kristen M.; Brüschweiler, Rafael; Miller, Brian G.

2015-01-01

Cooperativity in human glucokinase (GCK), the body’s primary glucose sensor and a major determinant of glucose homeostatic diseases, is fundamentally different from textbook models of allostery because GCK is monomeric and contains only one glucose-binding site. Prior work has demonstrated that millisecond timescale order-disorder transitions within the enzyme’s small domain govern cooperativity. Here, using limited proteolysis, we map the site of disorder in unliganded GCK to a 30-residue active-site loop that closes upon glucose binding. Positional randomization of the loop, coupled with genetic selection in a glucokinase-deficient bacterium, uncovers a hyperactive GCK variant with substantially reduced cooperativity. Biochemical and structural analysis of this loop variant and GCK variants associated with hyperinsulinemic hypoglycemia reveal two distinct mechanisms of enzyme activation. In α-type activation, glucose affinity is increased, the proteolytic susceptibility of the active site loop is suppressed and the 1H-13C heteronuclear multiple quantum coherence (HMQC) spectrum of 13C-Ile–labeled enzyme resembles the glucose-bound state. In β-type activation, glucose affinity is largely unchanged, proteolytic susceptibility of the loop is enhanced, and the 1H-13C HMQC spectrum reveals no perturbation in ensemble structure. Leveraging both activation mechanisms, we engineer a fully noncooperative GCK variant, whose functional properties are indistinguishable from other hexokinase isozymes, and which displays a 100-fold increase in catalytic efficiency over wild-type GCK. This work elucidates specific structural features responsible for generating allostery in a monomeric enzyme and suggests a general strategy for engineering cooperativity into proteins that lack the structural framework typical of traditional allosteric systems. PMID:26283387

Dual allosteric activation mechanisms in monomeric human glucokinase.

PubMed

Whittington, A Carl; Larion, Mioara; Bowler, Joseph M; Ramsey, Kristen M; Brüschweiler, Rafael; Miller, Brian G

2015-09-15

Cooperativity in human glucokinase (GCK), the body's primary glucose sensor and a major determinant of glucose homeostatic diseases, is fundamentally different from textbook models of allostery because GCK is monomeric and contains only one glucose-binding site. Prior work has demonstrated that millisecond timescale order-disorder transitions within the enzyme's small domain govern cooperativity. Here, using limited proteolysis, we map the site of disorder in unliganded GCK to a 30-residue active-site loop that closes upon glucose binding. Positional randomization of the loop, coupled with genetic selection in a glucokinase-deficient bacterium, uncovers a hyperactive GCK variant with substantially reduced cooperativity. Biochemical and structural analysis of this loop variant and GCK variants associated with hyperinsulinemic hypoglycemia reveal two distinct mechanisms of enzyme activation. In α-type activation, glucose affinity is increased, the proteolytic susceptibility of the active site loop is suppressed and the (1)H-(13)C heteronuclear multiple quantum coherence (HMQC) spectrum of (13)C-Ile-labeled enzyme resembles the glucose-bound state. In β-type activation, glucose affinity is largely unchanged, proteolytic susceptibility of the loop is enhanced, and the (1)H-(13)C HMQC spectrum reveals no perturbation in ensemble structure. Leveraging both activation mechanisms, we engineer a fully noncooperative GCK variant, whose functional properties are indistinguishable from other hexokinase isozymes, and which displays a 100-fold increase in catalytic efficiency over wild-type GCK. This work elucidates specific structural features responsible for generating allostery in a monomeric enzyme and suggests a general strategy for engineering cooperativity into proteins that lack the structural framework typical of traditional allosteric systems.

Numerical modeling of coronal mass ejections based on various pre-event model atmospheres

NASA Technical Reports Server (NTRS)

Suess, S. T.; Wang, A. H.; Wu, S. T.; Poletto, G.

1994-01-01

We examine how the initial state (pre-event corona) affects the numerical MHD simulation for a coronal mass ejection (CME). Earlier simulations based on a pre-event corona with a homogeneous density and temperature distribution at lower boundary (i.e. solar surface) have been used to analyze the role of streamer properties in determining the characteristics of loop-like transients. The present paper extends these studies to show how a broader class of global coronal properties leads not only to different types of CME's, but also modifies the adjacent quiet corona and/or coronal holes. We consider four pre-event coronal cases: (1) Constant boundary conditions and a polytropic gas with gamma = 1.05; (2) Non-constant (latitude dependent) boundary conditions and a polytropic gas with gamma = 1.05; (3) Constant boundary conditions with a volumetric energy source and gamma = 1.67; (4) Non-constant (latitude dependent) boundary conditions with a volumetric energy source and gamma = 1.67. In all models, the pre-event magnetic fields separate the corona into closed field regions (streamers) and open field regions. The CME's initiation is simulated by introducing at the base of the corona, within the streamer region, a standard pressure pulse and velocity change. Boundary values are determined using MHD characteristic theory. The simulations show how different CME's, including loop-like transients, clouds, and bright rays, might occur. There are significant new features in comparison to published results. We conclude that the pre-event corona is a crucial factor in dictating CME's properties.

Numerical Modeling of Coronal Mass Ejections Based on Various Pre-event Model Atmospheres

NASA Technical Reports Server (NTRS)

Wang, A. H.; Wu, S. T.; Suess, S. T.; Poletto, G.

1995-01-01

We examine how the initial state (pre-event corona) affects the numerical MHD simulation for a coronal mass ejection (CME). Earlier simulations based on a pre-event corona with a homogeneous density and temperature distribution, at the lower boundary (i.e., solar surface) have been used to analyze the role of streamer properties in determining the characteristics of loop-like transients. The present paper extends these studies to show how a broader class of global coronal properties leads not only to different types of CME's, but also modifies the adjacent quiet corona and/or coronal holes. We consider four pre-event coronal cases: (1) constant boundary conditions and a polytropic gas with gamma = 1.05; (2) non-constant (latitude dependent) boundary conditions and a polytropic gas with gamma = 1.05; (3) constant boundary conditions with a volumetric energy source and gamma = 1.67; (4) non-constant (latitude dependent) boundary conditions with a volumetric energy source and gamma = 1.67. In all models, the pre-event magnetic fields separate the corona into closed field regions (streamers) and open field regions. The CME's initiation is simulated by introducing at the base of the corona, within the streamer region, a standard pressure pulse and velocity change. Boundary values are determined using magnetohydrodynamic (MHD) characteristic theory. The simulations show how different CME's, including loop-like transients, clouds and bright rays, might occur. There are significant new features in comparison to published results. We conclude that the pre-event corona is a crucial factor in dictating CME's properties.

Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond

PubMed Central

D'hondt, Catheleyne; Iyyathurai, Jegan; Himpens, Bernard; Leybaert, Luc; Bultynck, Geert

2014-01-01

Intercellular communication in primary bovine corneal endothelial cells (BCECs) is mainly driven by the release of extracellular ATP through Cx43 hemichannels. Studying the characteristics of Ca2+-wave propagation in BCECs, an important form of intercellular communication, in response to physiological signaling events has led to the discovery of important insights in the functional properties and regulation of native Cx43 hemichannels. Together with ectopic expression models for Cx43 hemichannels and truncated/mutated Cx43 versions, it became very clear that loop/tail interactions play a key role in controlling the activity of Cx43 hemichannels. Interestingly, the negative regulation of Cx43 hemichannels by enhanced actin/myosin contractility seems to impinge upon loss of these loop/tail interactions essential for opening Cx43 hemichannels. Finally, these molecular insights have spurred the development of novel peptide tools that can selectively inhibit Cx43 hemichannels, but neither Cx43 gap junctions nor hemichannels formed by other Cx isoforms. These tools now set the stage to hunt for novel physiological functions for Cx43 hemichannels in primary cells and tissues and to tackle disease conditions associated with excessive, pathological Cx43-hemichannel openings. PMID:25309448

Feasibility of a Hybrid Brain-Computer Interface for Advanced Functional Electrical Therapy

PubMed Central

Savić, Andrej M.; Malešević, Nebojša M.; Popović, Mirjana B.

2014-01-01

We present a feasibility study of a novel hybrid brain-computer interface (BCI) system for advanced functional electrical therapy (FET) of grasp. FET procedure is improved with both automated stimulation pattern selection and stimulation triggering. The proposed hybrid BCI comprises the two BCI control signals: steady-state visual evoked potentials (SSVEP) and event-related desynchronization (ERD). The sequence of the two stages, SSVEP-BCI and ERD-BCI, runs in a closed-loop architecture. The first stage, SSVEP-BCI, acts as a selector of electrical stimulation pattern that corresponds to one of the three basic types of grasp: palmar, lateral, or precision. In the second stage, ERD-BCI operates as a brain switch which activates the stimulation pattern selected in the previous stage. The system was tested in 6 healthy subjects who were all able to control the device with accuracy in a range of 0.64–0.96. The results provided the reference data needed for the planned clinical study. This novel BCI may promote further restoration of the impaired motor function by closing the loop between the “will to move” and contingent temporally synchronized sensory feedback. PMID:24616644

The role of ANK interactions with MYBBP1a and SPHK1 in catabolic events of articular chondrocytes.

PubMed

Minashima, T; Campbell, K A; Hadley, S R; Zhang, Y; Kirsch, T

2014-06-01

To determine the role of progressive ankylosis protein (ANK)/Myb-binding protein 1a (MYBBP1a) and sphingosine kinase 1 (SPHK1) interactions in catabolic events of articular chondrocytes. ANK/MYBBP1a and SPHK1 interactions were identified using yeast two-hybrid screening and co-immunoprecipitation. To determine the role of these interactions in catabolic events of articular chondrocytes, ank/ank and wild type (WT) mouse chondrocytes transfected with full-length or mutant ank expression vectors (EVs) or femoral heads were treated with interleukin-1beta (IL-1β) in the absence or presence of SPHK inhibitor. Catabolic marker mRNA levels were analyzed by real time PCR; proteoglycan loss using safranin O staining and MMP-13 immunostaining were determined in femoral head explants; NF-κB activity was determined by transfecting chondrocytes with an NF-κB-specific luciferase reporter and analyzing nuclear translocation of p65 by immunoblotting; MYBBP1a nuclear or cytoplasmic amounts were determined by immunohistochemistry and immunoblotting. The ANK N-terminal region interacted with SPHK1, whereas a cytoplasmic C-terminal loop interacted with MYBBP1a. Lack of ANK/MYBBP1a and SPHK1 interactions in ank/ank chondrocytes resulted in increased MYBBP1a nuclear amounts and decreased SPHK1 activity, and consequently decreased NF-κB activity, catabolic marker mRNA levels, proteoglycan loss, and MMP-13 immunostaining in IL-1β-treated articular chondrocytes or femoral heads. Transfection with full-length ank EV reduced nuclear MYBBP1a amounts and fully restored SPHK and NF-κB activities in IL-1β-treated ank/ank chondrocytes, whereas transfection with P5L or F376del mutant ank reduced nuclear MYBBP1a or increased SPHK activity, respectively, and consequently either transfection only partially restored NF-κB activity. ANK/MYBBP1a and SPHK1 interactions stimulate catabolic events in IL-1β-mediated cartilage degradation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Note: Low phase noise programmable phase-locked loop with high temperature stability.

PubMed

Michálek, Vojtěch; Procházka, Ivan

2017-03-01

The design and construction of low jitter programmable phase-locked loop with low temperature coefficient of phase are presented. It has been designed for demanding high precision timing applications, especially as a clock source for event timer with subpicosecond precision. The phase-locked loop itself has a jitter of few hundreds of femtoseconds. It produces square wave with programmable output frequency from 100 MHz to 500 MHz and programmable amplitude of 0.25 V to 1.2 V peak-to-peak, which is locked to 5 MHz or 10 MHz reference frequency common for disciplined oscillators and highly stable clocks such as hydrogen maser. Moreover, it comprises an on-board temperature compensated crystal oscillator for stand-alone usage. The device provides temperature coefficient of the phase lock of 0.9 ps/K near room temperature.

A Method for Precision Closed-Loop Irrigation Using a Modified PID Control Algorithm

NASA Astrophysics Data System (ADS)

Goodchild, Martin; Kühn, Karl; Jenkins, Malcolm; Burek, Kazimierz; Dutton, Andrew

2016-04-01

The benefits of closed-loop irrigation control have been demonstrated in grower trials which show the potential for improved crop yields and resource usage. Managing water use by controlling irrigation in response to soil moisture changes to meet crop water demands is a popular approach but requires knowledge of closed-loop control practice. In theory, to obtain precise closed-loop control of a system it is necessary to characterise every component in the control loop to derive the appropriate controller parameters, i.e. proportional, integral & derivative (PID) parameters in a classic PID controller. In practice this is often difficult to achieve. Empirical methods are employed to estimate the PID parameters by observing how the system performs under open-loop conditions. In this paper we present a modified PID controller, with a constrained integral function, that delivers excellent regulation of soil moisture by supplying the appropriate amount of water to meet the needs of the plant during the diurnal cycle. Furthermore, the modified PID controller responds quickly to changes in environmental conditions, including rainfall events which can result in: controller windup, under-watering and plant stress conditions. The experimental work successfully demonstrates the functionality of a constrained integral PID controller that delivers robust and precise irrigation control. Coir substrate strawberry growing trial data is also presented illustrating soil moisture control and the ability to match water deliver to solar radiation.

Cell dynamics in cervical loop epithelium during transition from crown to root: implications for Hertwig's epithelial root sheath formation.

PubMed

Sakano, M; Otsu, K; Fujiwara, N; Fukumoto, S; Yamada, A; Harada, H

2013-04-01

Some clinical cases of hypoplastic tooth root are congenital. Because the formation of Hertwig's epithelial root sheath (HERS) is an important event for root development and growth, we have considered that understanding the HERS developmental mechanism contributes to elucidate the causal factors of the disease. To find integrant factors and phenomenon for HERS development and growth, we studied the proliferation and mobility of the cervical loop (CL). We observed the cell movement of CL by the DiI labeling and organ culture system. To examine cell proliferation, we carried out immunostaining of CL and HERS using anti-Ki67 antibody. Cell motility in CL was observed by tooth germ slice organ culture using green fluorescent protein mouse. We also examined the expression of paxillin associated with cell movement. Imaging using DiI labeling showed that, at the apex of CL, the epithelium elongated in tandem with the growth of outer enamel epithelium (OEE). Cell proliferation assay using Ki67 immunostaining showed that OEE divided more actively than inner enamel epithelium (IEE) at the onset of HERS formation. Live imaging suggested that mobility of the OEE and cells in the apex of CL were more active than in IEE. The expression of paxillin was observed strongly in OEE and the apex of CL. The more active growth and movement of OEE cells contributed to HERS formation after reduction of the growth of IEE. The expression pattern of paxillin was involved in the active movement of OEE and HERS. The results will contribute to understand the HERS formation mechanism and elucidate the cause of anomaly root. © 2012 John Wiley & Sons A/S.

Crosstalk between mTORC1 and cAMP Signaling

DTIC Science & Technology

2016-09-01

2010). It has been suggested that the low mTOR activity retained under moderate hyper - tonic conditions facilitates the expression of some osmo...member of the MAP kinase (MAPK) subfamily. It is notable that the activation loop ofNLK protein possesses the sequence Thr–Gln–Glu (TQE) motif...Ishitani et al. 2011). Thus, NLK can be activated without being phosphorylated in the activation loop by upstream kinases. Moreover, high levels of

A description of communication patterns during CPR in ICU.

PubMed

Taylor, Katherine L; Ferri, Susan; Yavorska, Tatyana; Everett, Tobias; Parshuram, Christopher

2014-10-01

Deficiencies in communication in health care are a common source of medical error. Preferred communication patterns are a component of resuscitation teaching. We audio-recorded resuscitations in a mixed paediatric medical and surgical ICU to describe communication. In the intensive care unit, resuscitation events were prospectively audio-recorded by two trained observers (using handheld recorders). Recordings were transcribed and anonymised within 24h. We grouped utterances regarding the same subject matter from beginning (irrespective of response) as a communication epoch. For each epoch, we describe the initiator, audience and content of message. Teamwork behaviours were described using Anesthesia Nontechnical Skills framework (ANTS), a behavioural marker system for crisis-resource management. Consent rates from staff were 139/140 (99%) and parents were 67/92 (73%). We analysed 36min 57s of audio dialogue from 4 cardiac arrest events in 363h of prospective screening. There were 180 communication epochs (1 every 12s): 100 (56%) from the team-leader and 80 (44%) from non-team-leader(s). Team-leader epochs were to give or confirm orders or assert authority (61%), clarify patient history (14%) and provide clinical updates (25%). Non-team-leader epochs were more often directed to the team (65%) than the team-leader (35%). Audio-recordings provided information for 80% of the ANTS component elements with scores of 2-4. Communication epochs were frequent, most from the team-leader. We identified an 'outer loop' of communication between team members not including the team-leader, responsible for 44% of all communication events. We discuss difficulties in this research methodology. Future work includes exploring the process of the 'outer loop' by resuscitation team members to evaluate the optimal balance between single leader and team suggestions, the content of the outer loop discussions and in-event communication strategies to improve outcomes. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

Well-observed dynamics of flaring and peripheral coronal magnetic loops during an M-class limb flare

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

Shen, Jinhua; Zhou, Tuanhui; Ji, Haisheng

2014-08-20

In this paper, we present a variety of well-observed dynamic behaviors for the flaring and peripheral magnetic loops of the M6.6 class extreme limb flare that occurred on 2011 February 24 (SOL2011-02-24T07:20) from EUV observations by the Atmospheric Imaging Assembly on the Solar Dynamics Observatory and X-ray observations by RHESSI. The flaring loop motion confirms the earlier contraction-expansion picture. We find that the U-shaped trajectory delineated by the X-ray corona source of the flare roughly follows the direction of a filament eruption associated with the flare. Different temperature structures of the coronal source during the contraction and expansion phases stronglymore » suggest different kinds of magnetic reconnection processes. For some peripheral loops, we discover that their dynamics are closely correlated with the filament eruption. During the slow rising to abrupt, fast rising of the filament, overlying peripheral magnetic loops display different responses. Two magnetic loops on the elbow of the active region had a slow descending motion followed by an abrupt successive fast contraction, while magnetic loops on the top of the filament were pushed outward, slowly being inflated for a while and then erupting as a moving front. We show that the filament activation and eruption play a dominant role in determining the dynamics of the overlying peripheral coronal magnetic loops.« less

Dressing the Coronal Magnetic Extrapolations of Active Regions with a Parameterized Thermal Structure

NASA Astrophysics Data System (ADS)

Nita, Gelu M.; Viall, Nicholeen M.; Klimchuk, James A.; Loukitcheva, Maria A.; Gary, Dale E.; Kuznetsov, Alexey A.; Fleishman, Gregory D.

2018-01-01

The study of time-dependent solar active region (AR) morphology and its relation to eruptive events requires analysis of imaging data obtained in multiple wavelength domains with differing spatial and time resolution, ideally in combination with 3D physical models. To facilitate this goal, we have undertaken a major enhancement of our IDL-based simulation tool, GX_Simulator, previously developed for modeling microwave and X-ray emission from flaring loops, to allow it to simulate quiescent emission from solar ARs. The framework includes new tools for building the atmospheric model and enhanced routines for calculating emission that include new wavelengths. In this paper, we use our upgraded tool to model and analyze an AR and compare the synthetic emission maps with observations. We conclude that the modeled magneto-thermal structure is a reasonably good approximation of the real one.

Not even wrong: A philosophical, historical and ultimately a scientific inquiry into the Schmidt Law

NASA Astrophysics Data System (ADS)

Madore, Barry F.; Carlson, Erika K.

2017-03-01

We introduce a novel approach to interpreting the well-known spatial correlation of gas densities with on-going star formation. Treated as a closed-loop process involving two physically distinct phases the data can be subdivided into regions that are active and those that are quiescent. The active regions can be distinguished by the presence of high-mass, short-lived, but recently-formed OB stars; the quiescent regions are marked by an absence of these stars and they are considered to be recovering from the last star-formation event and are re-collapsing. The relative (areal) frequencies of those two phases are directly proportional to the relative timescales. For four Local Group galaxies, NGC 6822, the Large & Small Magellanic Clouds, and M33, the cloud assembly/collapse timescales are all found to be monotonically decreasing power-law functions of density, with as yet to be explained differences.

Leading-Color Fully Differential Two-Loop Soft Corrections to QCD Dipole Showers

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

Dulat, Falko; Höche, Stefan; Prestel, Stefan

We compute the next-to-leading order corrections to soft-gluon radiation differentially in the one-emission phase space. We show that their contribution to the evolution of color dipoles can be obtained in a modified subtraction scheme, such that both one- and two-emission terms are amenable to Monte-Carlo integration. The two-loop cusp anomalous dimension is recovered naturally upon integration over the full phase space. We present two independent implementations of the new algorithm in the two event generators Pythia and Sherpa, and we compare the resulting fully differential simulation to the CMW scheme.

Affective loop experiences: designing for interactional embodiment.

PubMed

Höök, Kristina

2009-12-12

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves-the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives. The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for 'open' surfaces in the design that can carry users' own meaning-making processes, how to combine modalities to create for a 'unity' of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences. But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and experienced inseparable from all other aspects of everyday life. Emotion processes are part of our social ways of being in the world; they dye our dreams, hopes and bodily experiences of the world. If we aim to design for affective interaction experiences, we need to place them into this larger picture.

Affective loop experiences: designing for interactional embodiment

PubMed Central

Höök, Kristina

2009-01-01

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves—the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives. The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for ‘open’ surfaces in the design that can carry users' own meaning-making processes, how to combine modalities to create for a ‘unity’ of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences. But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and experienced inseparable from all other aspects of everyday life. Emotion processes are part of our social ways of being in the world; they dye our dreams, hopes and bodily experiences of the world. If we aim to design for affective interaction experiences, we need to place them into this larger picture. PMID:19884153

Enthalpy-Based Thermal Evolution of Loops: II. Improvements to the Model

NASA Technical Reports Server (NTRS)

Cargill, P. J.; Bradshaw, S. J.; Klimchuk, J. A.

2011-01-01

This paper further develops the zero-dimensional (0D) hydrodynamic coronal loop model "Enthalpy-based Thermal Evolution of Loops" (EBTEL) originally proposed by Klimchuk et al (2008), which studies the plasma response to evolving coronal heating. It has typically been applied to impulsive heating events. The basis of EBTEL is the modelling of mass exchange between the corona and transition region and chromosphere in response to heating variations, with the key parameter being the ratio of transition region to coronal radiation. We develop new models for this parameter that now include gravitational stratification and a physically motivated approach to radiative cooling. A number of examples are presented, including nanoflares in short and long loops, and a small flare. It is found that while the evolution of the loop temperature is rather insensitive to the details of the model, accurate tracking of the density requires the inclusion of our new features. In particular, we are able to now obtain highly over-dense loops in the late cooling phase and decreases to the coronal density arising due to stratification. The 0D results are compared to a 1D hydro code (Hydrad). The agreement is acceptable, with the exception of the flare case where some versions of Hydrad can give significantly lower densities. This is attributed to the method used to model the chromosphere in a flare. EBTEL is suitable for general use as a tool for (a) quick-look results of loop evolution in response to a given heating function and (b) situations where the modelling of hundreds or thousands of elemental loops is needed. A single run takes a few seconds on a contemporary laptop.

On Event-Triggered Adaptive Architectures for Decentralized and Distributed Control of Large-Scale Modular Systems

PubMed Central

Albattat, Ali; Gruenwald, Benjamin C.; Yucelen, Tansel

2016-01-01

The last decade has witnessed an increased interest in physical systems controlled over wireless networks (networked control systems). These systems allow the computation of control signals via processors that are not attached to the physical systems, and the feedback loops are closed over wireless networks. The contribution of this paper is to design and analyze event-triggered decentralized and distributed adaptive control architectures for uncertain networked large-scale modular systems; that is, systems consist of physically-interconnected modules controlled over wireless networks. Specifically, the proposed adaptive architectures guarantee overall system stability while reducing wireless network utilization and achieving a given system performance in the presence of system uncertainties that can result from modeling and degraded modes of operation of the modules and their interconnections between each other. In addition to the theoretical findings including rigorous system stability and the boundedness analysis of the closed-loop dynamical system, as well as the characterization of the effect of user-defined event-triggering thresholds and the design parameters of the proposed adaptive architectures on the overall system performance, an illustrative numerical example is further provided to demonstrate the efficacy of the proposed decentralized and distributed control approaches. PMID:27537894

On Event-Triggered Adaptive Architectures for Decentralized and Distributed Control of Large-Scale Modular Systems.

PubMed

Albattat, Ali; Gruenwald, Benjamin C; Yucelen, Tansel

2016-08-16

The last decade has witnessed an increased interest in physical systems controlled over wireless networks (networked control systems). These systems allow the computation of control signals via processors that are not attached to the physical systems, and the feedback loops are closed over wireless networks. The contribution of this paper is to design and analyze event-triggered decentralized and distributed adaptive control architectures for uncertain networked large-scale modular systems; that is, systems consist of physically-interconnected modules controlled over wireless networks. Specifically, the proposed adaptive architectures guarantee overall system stability while reducing wireless network utilization and achieving a given system performance in the presence of system uncertainties that can result from modeling and degraded modes of operation of the modules and their interconnections between each other. In addition to the theoretical findings including rigorous system stability and the boundedness analysis of the closed-loop dynamical system, as well as the characterization of the effect of user-defined event-triggering thresholds and the design parameters of the proposed adaptive architectures on the overall system performance, an illustrative numerical example is further provided to demonstrate the efficacy of the proposed decentralized and distributed control approaches.

Functional significance of the E loop, a novel motif conserved in the lantibiotic immunity ATP-binding cassette transport systems.

PubMed

Okuda, Ken-ichi; Yanagihara, Sae; Sugayama, Tomomichi; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

2010-06-01

Lantibiotics are peptide-derived antibacterial substances produced by some Gram-positive bacteria and characterized by the presence of unusual amino acids, like lanthionines and dehydrated amino acids. Because lantibiotic producers may be attacked by self-produced lantibiotics, they express immunity proteins on the cytoplasmic membrane. An ATP-binding cassette (ABC) transport system mediated by the LanFEG protein complex is a major system in lantibiotic immunity. Multiple-sequence alignment analysis revealed that LanF proteins contain the E loop, a variant of the Q loop, which is a well-conserved motif in the nucleotide-binding domains (NBDs) of general ABC transporters. To elucidate E loop function, we introduced a mutation in the NukF protein, which is involved in the nukacin-ISK-1 immunity system. Amino acid replacement of glutamic acid in the E loop with glutamine (E85Q) resulted in slight decreases in the immunity level and transport activity. Additionally, the E85A mutation severely impaired the immunity level and transport activity. On the other hand, ATPase activities of purified E85Q and E85A mutants were almost similar to that of the wild type. These results suggested that the E loop found in ABC transporters involved in lantibiotic immunity plays a significant role in the function of these transporters, especially in the structural change of transmembrane domains.

On the Occurrence of Thermal Nonequilibrium in Coronal Loops

NASA Astrophysics Data System (ADS)

Froment, C.; Auchère, F.; Mikić, Z.; Aulanier, G.; Bocchialini, K.; Buchlin, E.; Solomon, J.; Soubrié, E.

2018-03-01

Long-period EUV pulsations, recently discovered to be common in active regions, are understood to be the coronal manifestation of thermal nonequilibrium (TNE). The active regions previously studied with EIT/Solar and Heliospheric Observatory and AIA/SDO indicated that long-period intensity pulsations are localized in only one or two loop bundles. The basic idea of this study is to understand why. For this purpose, we tested the response of different loop systems, using different magnetic configurations, to different stratifications and strengths of the heating. We present an extensive parameter-space study using 1D hydrodynamic simulations (1020 in total) and conclude that the occurrence of TNE requires specific combinations of parameters. Our study shows that the TNE cycles are confined to specific ranges in parameter space. This naturally explains why only some loops undergo constant periodic pulsations over several days: since the loop geometry and the heating properties generally vary from one loop to another in an active region, only the ones in which these parameters are compatible exhibit TNE cycles. Furthermore, these parameters (heating and geometry) are likely to vary significantly over the duration of a cycle, which potentially limits the possibilities of periodic behavior. This study also confirms that long-period intensity pulsations and coronal rain are two aspects of the same phenomenon: both phenomena can occur for similar heating conditions and can appear simultaneously in the simulations.

Active control of one or more EGR loops

DOEpatents

Ruth, Michael J.; Cunningham, Michael J.; Henry, Cary A.

2017-08-08

Active control of one or more exhaust gas recirculation loops is provided to manage and EGR fraction in the charge flow to produce desired operating conditions and/or provide diagnostics in response to at least one of an oxygen concentration and a NOx concentration in the charge flow and in the exhaust flow.

First Imaging Observation of Standing Slow Wave in Coronal Fan Loops

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

Pant, V.; Tiwari, A.; Banerjee, D.

2017-09-20

We observe intensity oscillations along coronal fan loops associated with the active region AR 11428. The intensity oscillations were triggered by blast waves that were generated due to X-class flares in the distant active region AR 11429. To characterize the nature of oscillations, we created time–distance maps along the fan loops and noted that the intensity oscillations at two ends of the loops were out of phase. As we move along the fan loop, the amplitude of the oscillations first decreased and then increased. The out-of-phase nature together with the amplitude variation along the loop implies that these oscillations aremore » very likely to be standing waves. The period of the oscillations is estimated to be ∼27 minutes, damping time to be ∼45 minutes, and phase velocity projected in the plane of sky to be ∼65–83 km s{sup −1}. The projected phase speeds were in the range of the acoustic speed of coronal plasma at about 0.6 MK, which further indicates that these are slow waves. To the best of our knowledge, this is the first report on the existence of the standing slow waves in non-flaring fan loops.« less

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains

PubMed Central

Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

2016-01-01

Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS. PMID:27924253

Design and development of a geo-referenced database to radionuclides in food

NASA Astrophysics Data System (ADS)

Nascimento, L. M. E.; Ferreira, A. C. M.; Gonzalez, S. A.

2018-03-01

The primary purpose of the range of activities concerning the info management of the environmental assessment is to provide to scientific community an improved access to environmental data, as well as to support the decision making loop, in case of contamination events due either to accidental or intentional causes. In recent years, geotechnologies became a key reference in environmental research and monitoring, since they deliver an efficient data retrieval and subsequent processing about natural resources. This study aimed at the development of a georeferenced database (SIGLARA – SIstema Georeferenciado Latino Americano de Radionuclídeos em Alimentos), designed to radioactivity in food data storage, available in three languages (Spanish, Portuguese and English), employing free software[l].

Evidence for Widespread Cooling in an Active Region Observed with the SDO Atmospheric Imaging Assembly

NASA Technical Reports Server (NTRS)

Viall, Nicholeen M.; Klimchuk, James A.

2012-01-01

A well known behavior of EUV light curves of discrete coronal loops is that the peak intensities of cooler channels or spectral lines are reached at progressively later times. This time lag is understood to be the result of hot coronal loop plasma cooling through these lower respective temperatures. However, loops typically comprise only a minority of the total emission in active regions. Is this cooling pattern a common property of active region coronal plasma, or does it only occur in unique circumstances, locations, and times? The new SDO/AIA data provide a wonderful opportunity to answer this question systematically for an entire active region. We measure the time lag between pairs of SDO/AIA EUV channels using 24 hours of images of AR 11082 observed on 19 June 2010. We find that there is a time-lag signal consistent with cooling plasma, just as is usually found for loops, throughout the active region including the diffuse emission between loops for the entire 24 hour duration. The pattern persists consistently for all channel pairs and choice of window length within the 24 hour time period, giving us confidence that the plasma is cooling from temperatures of greater than 3 MK, and sometimes exceeding 7 MK, down to temperatures lower than approx. 0.8 MK. This suggests that the bulk of the emitting coronal plasma in this active region is not steady; rather, it is dynamic and constantly evolving. These measurements provide crucial constraints on any model which seeks to describe coronal heating.

Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations

PubMed Central

McDowell, S. Elizabeth; Jun, Jesse M.; Walter, Nils G.

2010-01-01

Enzymes generally are thought to derive their functional activity from conformational motions. The limited chemical variation in RNA suggests that such structural dynamics may play a particularly important role in RNA function. Minimal hammerhead ribozymes are known to cleave efficiently only in ∼10-fold higher than physiologic concentrations of Mg2+ ions. Extended versions containing native loop–loop interactions, however, show greatly enhanced catalytic activity at physiologically relevant Mg2+ concentrations, for reasons that are still ill-understood. Here, we use Mg2+ titrations, activity assays, ensemble, and single molecule fluorescence resonance energy transfer (FRET) approaches, combined with molecular dynamics (MD) simulations, to ask what influence the spatially distant tertiary loop–loop interactions of an extended hammerhead ribozyme have on its structural dynamics. By comparing hammerhead variants with wild-type, partially disrupted, and fully disrupted loop–loop interaction sequences we find that the tertiary interactions lead to a dynamic motional sampling that increasingly populates catalytically active conformations. At the global level the wild-type tertiary interactions lead to more frequent, if transient, encounters of the loop-carrying stems, whereas at the local level they lead to an enrichment in favorable in-line attack angles at the cleavage site. These results invoke a linkage between RNA structural dynamics and function and suggest that loop–loop interactions in extended hammerhead ribozymes—and Mg2+ ions that bind to minimal ribozymes—may generally allow more frequent access to a catalytically relevant conformation(s), rather than simply locking the ribozyme into a single active state. PMID:20921269

Changes in basal ganglia processing of cortical input following magnetic stimulation in Parkinsonism.

PubMed

Tischler, Hadass; Moran, Anan; Belelovsky, Katya; Bronfeld, Maya; Korngreen, Alon; Bar-Gad, Izhar

2012-12-01

Parkinsonism is associated with major changes in neuronal activity throughout the cortico-basal ganglia loop. Current measures quantify changes in baseline neuronal and network activity but do not capture alterations in information propagation throughout the system. Here, we applied a novel non-invasive magnetic stimulation approach using a custom-made mini-coil that enabled us to study transmission of neuronal activity throughout the cortico-basal ganglia loop in both normal and parkinsonian primates. By magnetically perturbing cortical activity while simultaneously recording neuronal responses along the cortico-basal ganglia loop, we were able to directly investigate modifications in descending cortical activity transmission. We found that in both the normal and parkinsonian states, cortical neurons displayed similar multi-phase firing rate modulations in response to magnetic stimulation. However, in the basal ganglia, large synaptically driven stereotypic neuronal modulation was present in the parkinsonian state that was mostly absent in the normal state. The stimulation-induced neuronal activity pattern highlights the change in information propagation along the cortico-basal ganglia loop. Our findings thus point to the role of abnormal dynamic activity transmission rather than changes in baseline activity as a major component in parkinsonian pathophysiology. Moreover, our results hint that the application of transcranial magnetic stimulation (TMS) in human patients of different disorders may result in different neuronal effects than the one induced in normal subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

Conformational motions regulate phosphoryl transfer in related protein tyrosine phosphatases

PubMed Central

Whittier, Sean K.; Hengge, Alvan C.; Loria, J. Patrick

2014-01-01

Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using NMR spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates, however we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes. PMID:23970698

Application of active control landing gear technology to the A-10 aircraft

NASA Technical Reports Server (NTRS)

Ross, I.; Edson, R.

1983-01-01

Two concepts which reduce the A-10 aircraft's wing/gear interface forces as a result of applying active control technology to the main landing gear are described. In the first concept, referred to as the alternate concept a servovalve in a closed pressure control loop configuration effectively varies the size of the third stage spool valve orifice which is embedded in the strut. This action allows the internal energy in the strut to shunt hydraulic flow around the metering orifice. The command signal to the loop is reference strut pressure which is compared to the measured strut pressure, the difference being the loop error. Thus, the loop effectively varies the spool valve orifice size to maintain the strut pressure, and therefore minimizes the wing/gear interface force referenced.

Inverted Temperature Loops in The Quiet Corona: Properties and Physical Origin

NASA Astrophysics Data System (ADS)

Huang, Z.; van der Holst, B.; Frazin, R. A.; Nuevo, F.; Vásquez, A. M.; Manchester, W.; Sokolov, I.; Gombosi, T. I.

2013-12-01

Huang et al. 2012 revealed the existence of inverted temperature ("down") loops, in which temperature decreases with height, as well as the usual ("up") loops, in which the temperature increases with height, in the quiet solar Corona. It was shown that the "down" loops are mostly located at low latitudes and "up" loops most often appear in high latitudes. A recent study by Nuevo et al. 2013 confirmed this discovery and further showed that the "down" loop population is greatest at solar minimum; and strongly decreases with solar activity. Moreover, the "down" loops were found to be associated with values of the plasma beta greater than about unity, while the "up" loops were associated with much smaller values of beta. Here, we review the properties of "up" and "down" loops, and employ a state-of-the-art global MHD model to understand the physics of these loops as well as to investigate their thermodynamic stability. The 3D MHD model uses a phenomenological wave dissipation model based on wave reflection (proportional to the Alfvén speed gradients) and turbulent dissipation.

FORWARD MODELING OF STANDING KINK MODES IN CORONAL LOOPS. II. APPLICATIONS

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

Yuan, Ding; Doorsselaere, Tom Van, E-mail: DYuan2@uclan.ac.uk

2016-04-15

Magnetohydrodynamic waves are believed to play a significant role in coronal heating, and could be used for remote diagnostics of solar plasma. Both the heating and diagnostic applications rely on a correct inversion (or backward modeling) of the observables into the thermal and magnetic structures of the plasma. However, due to the limited availability of observables, this is an ill-posed issue. Forward modeling is designed to establish a plausible mapping of plasma structuring into observables. In this study, we set up forward models of standing kink modes in coronal loops and simulate optically thin emissions in the extreme ultraviolet bandpasses,more » and then adjust plasma parameters and viewing angles to match three events of transverse loop oscillations observed by the Solar Dynamics Observatory/Atmospheric Imaging Assembly. We demonstrate that forward models could be effectively used to identify the oscillation overtone and polarization, to reproduce the general profile of oscillation amplitude and phase, and to predict multiple harmonic periodicities in the associated emission intensity and loop width variation.« less

Importance of inhibiting sodium-glucose cotransporter and its compelling indication in type 2 diabetes: pathophysiological hypothesis.

PubMed

Kimura, Genjiro

2016-03-01

Primarily the sodium-glucose cotransporter 2 (SGLT2) inhibitors suppress the cotransport of glucose and sodium from the tubular lumen of proximal tubules to the blood and enhance the glucose excretion into urine. Therefore, glucose and caloric balances become negative, making the blood glucose level as well as insulin secretion both reduced. On the other hand, the proximal tubular fluid, constituting with low chloride concentration because of SGLT2 inhibition, is transferred to the loop of Henle. On the low chloride conditions, the reabsorption mechanisms in the loop of Henle do not work, as if loop diuretics are given. Finally, blood pressure is also lowered secondarily due to the loop diuretic action by SGLT2 inhibitions. Thus, the metabolic and hemodynamic combined systems synergistically interact further to suppress the risks leading to atherosclerosis and organs damage. Precise mechanisms for SGLT2 inhibitors to work in various aspects especially in preventing organ damage and cardiovascular events must be clarified further. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Efficacy of different types of self-expandable stents in carotid artery stenting for carotid bifurcation stenosis.

PubMed

Liu, Ya-min; Qin, Hao; Zhang, Bo; Wang, Yu-jing; Feng, Jun; Wu, Xiang

2016-02-01

Both open and closed loop self-expandable stents were used in carotid artery stenting (CAS) for carotid bifurcation stenosis. We sought to compare the efficacy of two types of stents in CAS. The data of 212 patients treated with CAS (42 and 170 cases implanted with closed and open loop stents, respectively) for carotid bifurcation stenosis and distal filtration protection devices were retrospectively analyzed. Between closed and open loop stents, there were no significant differences in hospitalization duration, NIHSS score before and after the treatment, stenosis at 12th month, and cumulative incidence of primary endpoint events within 30 days or from the 31st day to the 12th month; while there were significant differences in hemodynamic changes and rate of difficulty in recycling distal filtration protection devices. Use of open vs. closed loop stents for carotid bifurcation stenosis seems to be associated with similar incidence of complications, except for greater rate of hemodynamic changes and lower rate of difficulty in recycling the distal filtration protection devices.

And the Humans Save the Day or Maybe They Ruin It: The Importance of Humans in the Loop

NASA Technical Reports Server (NTRS)

DeMott, Diana; Boyer, Roger; Bigler, Mark

2017-01-01

Flying a mission in space requires a massive commitment of resources, and without the talent and commitment of the people involved in this effort we would never leave the atmosphere of Earth. When we use the phrase "humans in the loop", it could apply to almost any endeavor since everything starts with humans developing a concept, completing the design process, building or implementing a product and using the product to achieve a goal or purpose. Narrowing the focus to spaceflights, there are a variety of individuals involved throughout the preparations for flight and the flight itself. All of the humans involved add value and support for program success. The purpose of this paper focuses on how a Probabilistic Risk Assessment (PRA) accounts for the human in the loop for potential missions using a technique called Human Reliability Analysis (HRA). Human actions can increase or decrease the overall risk via initiating events or mitigating them, thus removing the human from the loop doesn't always lower the risk.

Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops.

PubMed

Lang, Walter H; Coats, Julie E; Majka, Jerzy; Hura, Greg L; Lin, Yuyen; Rasnik, Ivan; McMurray, Cynthia T

2011-10-18

Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation.

The structural coupling between ATPase activation and recovery stroke in the myosin II motor

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

Koppole, Sampath; Smith, Jeremy C; Fischer, S.

2007-07-01

Before the myosin motor head can perform the next power stroke, it undergoes a large conformational transition in which the converter domain, bearing the lever arm, rotates {approx} 65{sup o}. Simultaneous with this 'recovery stroke', myosin activates its ATPase function by closing the Switch-2 loop over the bound ATP. This coupling between the motions of the converter domain and of the 40 {angstrom}-distant Switch-2 loop is essential to avoid unproductive ATP hydrolysis. The coupling mechanism is determined here by finding a series of optimized intermediates between crystallographic end structures of the recovery stroke (Dictyostelium discoideum), yielding movies of the transitionmore » at atomic detail. The successive formation of two hydrogen bonds by the Switch-2 loop is correlated with the successive see-saw motions of the relay and SH1 helices that hold the converter domain. SH1 helix and Switch-2 loop communicate via a highly conserved loop that wedges against the SH1-helix upon Switch-2 closing.« less

The structural coupling between ATPase activation and recovery stroke in the myosin II motor.

PubMed

Koppole, Sampath; Smith, Jeremy C; Fischer, Stefan

2007-07-01

Before the myosin motor head can perform the next power stroke, it undergoes a large conformational transition in which the converter domain, bearing the lever arm, rotates approximately 65 degrees . Simultaneous with this "recovery stroke," myosin activates its ATPase function by closing the Switch-2 loop over the bound ATP. This coupling between the motions of the converter domain and of the 40 A-distant Switch-2 loop is essential to avoid unproductive ATP hydrolysis. The coupling mechanism is determined here by finding a series of optimized intermediates between crystallographic end structures of the recovery stroke (Dictyostelium discoideum), yielding movies of the transition at atomic detail. The successive formation of two hydrogen bonds by the Switch-2 loop is correlated with the successive see-saw motions of the relay and SH1 helices that hold the converter domain. SH1 helix and Switch-2 loop communicate via a highly conserved loop that wedges against the SH1-helix upon Switch-2 closing.

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

DOE PAGES

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela; ...

2017-03-15

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

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

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation.

PubMed

Cobbaut, Mathias; Derua, Rita; Parker, Peter J; Waelkens, Etienne; Janssens, Veerle; Van Lint, Johan

2018-06-22

The protein kinase D (PKD) family is regulated through multi-site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser-742 (and Ser-738 in vitro) in the activation loop and Ser-910 in the C-tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P+1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance. In cells, PKD Tyr autophosphorylation is suppressed through the association of an inhibitory factor. Our findings provide important novel insights into PKD (auto)regulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique.

PubMed

Savvidou, Christiana; Tsai, Tsu-Min

2015-06-01

The purpose of this study is to report the clinical results after repair of flexor tendon zone II injuries utilizing a 6-strand double-loop technique and early post-operative active rehabilitation. We retrospectively reviewed 22 patients involving 51 cases with zone II flexor tendon repair using a six strand double loop technique from September 1996 to December 2012. Most common mechanism of injuries was sharp lacerations (86.5 %). Tendon injuries occurred equally in manual and non-manual workers and were work-related in 33 % of the cases. The Strickland score for active range of motion (ROM) postoperatively was excellent and good in the majority of the cases (81 %). The rupture rate was 1.9 %. The six strand double loop technique for Zone II flexor tendon repair leads to good and excellent motion in the majority of patients and low re- rupture rate. It is clinically effective and allows for early postoperative active rehabilitation.

Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement

PubMed Central

Sasaki, Atsuo T.; Chun, Cheryl; Takeda, Kosuke; Firtel, Richard A.

2004-01-01

During chemotaxis, receptors and heterotrimeric G-protein subunits are distributed and activated almost uniformly along the cell membrane, whereas PI(3,4,5)P3, the product of phosphatidylinositol 3-kinase (PI3K), accumulates locally at the leading edge. The key intermediate event that creates this strong PI(3,4,5)P3 asymmetry remains unclear. Here, we show that Ras is rapidly and transiently activated in response to chemoattractant stimulation and regulates PI3K activity. Ras activation occurs at the leading edge of chemotaxing cells, and this local activation is independent of the F-actin cytoskeleton, whereas PI3K localization is dependent on F-actin polymerization. Inhibition of Ras results in severe defects in directional movement, indicating that Ras is an upstream component of the cell's compass. These results support a mechanism by which localized Ras activation mediates leading edge formation through activation of basal PI3K present on the plasma membrane and other Ras effectors required for chemotaxis. A feedback loop, mediated through localized F-actin polymerization, recruits cytosolic PI3K to the leading edge to amplify the signal. PMID:15534002

Neutron Tomography Using Mobile Neutron Generators for Assessment of Void Distributions in Thermal Hydraulic Test Loops

NASA Astrophysics Data System (ADS)

Andersson, P.; Bjelkenstedt, T.; Sundén, E. Andersson; Sjöstrand, H.; Jacobsson-Svärd, S.

Detailed knowledge of the lateral distribution of steam (void) and water in a nuclear fuel assembly is of great value for nuclear reactor operators and fuel manufacturers, with consequences for both reactor safety and economy of operation. Therefore, nuclear relevant two-phase flows are being studied at dedicated thermal-hydraulic test loop, using two-phase flow systems ranging from simplified geometries such as heated circular pipes to full scale mock-ups of nuclear fuel assemblies. Neutron tomography (NT) has been suggested for assessment of the lateral distribution of steam and water in such test loops, motivated by a good ability of neutrons to penetrate the metallic structures of metal pipes and nuclear fuel rod mock-ups, as compared to e.g. conventional X-rays, while the liquid water simultaneously gives comparatively good contrast. However, these stationary test loops require the measurement setup to be mobile, which is often not the case for NT setups. Here, it is acknowledged that fast neutrons of 14 MeV from mobile neutron generators constitute a viable option for a mobile NT system. We present details of the development of neutron tomography for this purpose at the division of Applied Nuclear Physics at Uppsala University. Our concept contains a portable neutron generator, exploiting the fusion reaction of deuterium and tritium, and a detector with plastic scintillator elements designed to achieveadequate spatial and energy resolution, all mounted in a light-weight frame without collimators or bulky moderation to allow for a mobile instrument that can be moved about the stationary thermal hydraulic test sections. The detector system stores event-to-event pulse-height information to allow for discrimination based on the energy deposition in the scintillator elements.

Nanogeochronology of discordant zircon measured by atom probe microscopy of Pb-enriched dislocation loops

PubMed Central

Peterman, Emily M.; Reddy, Steven M.; Saxey, David W.; Snoeyenbos, David R.; Rickard, William D. A.; Fougerouse, Denis; Kylander-Clark, Andrew R. C.

2016-01-01

Isotopic discordance is a common feature in zircon that can lead to an erroneous age determination, and it is attributed to the mobilization and escape of radiogenic Pb during its post-crystallization geological evolution. The degree of isotopic discordance measured at analytical scales of ~10 μm often differs among adjacent analysis locations, indicating heterogeneous distributions of Pb at shorter length scales. We use atom probe microscopy to establish the nature of these sites and the mechanisms by which they form. We show that the nanoscale distribution of Pb in a ~2.1 billion year old discordant zircon that was metamorphosed c. 150 million years ago is defined by two distinct Pb reservoirs. Despite overall Pb loss during peak metamorphic conditions, the atom probe data indicate that a component of radiogenic Pb was trapped in 10-nm dislocation loops that formed during the annealing of radiation damage associated with the metamorphic event. A second Pb component, found outside the dislocation loops, represents homogeneous accumulation of radiogenic Pb in the zircon matrix after metamorphism. The 207Pb/206Pb ratios measured from eight dislocation loops are equivalent within uncertainty and yield an age consistent with the original crystallization age of the zircon, as determined by laser ablation spot analysis. Our results provide a specific mechanism for the trapping and retention of radiogenic Pb during metamorphism and confirm that isotopic discordance in this zircon is characterized by discrete nanoscale reservoirs of Pb that record different isotopic compositions and yield age data consistent with distinct geological events. These data may provide a framework for interpreting discordance in zircon as the heterogeneous distribution of discrete radiogenic Pb populations, each yielding geologically meaningful ages. PMID:27617295

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

Toeroek, T.; Aulanier, G.; Schmieder, B.

We address the formation of three-dimensional nullpoint topologies in the solar corona by combining Hinode/X-ray Telescope (XRT) observations of a small dynamic limb event, which occurred beside a non-erupting prominence cavity, with a three-dimensional (3D) zero-beta magnetohydrodynamics (MHD) simulation. To this end, we model the boundary-driven 'kinematic' emergence of a compact, intense, and uniformly twisted flux tube into a potential field arcade that overlies a weakly twisted coronal flux rope. The expansion of the emerging flux in the corona gives rise to the formation of a nullpoint at the interface of the emerging and the pre-existing fields. We unveil amore » two-step reconnection process at the nullpoint that eventually yields the formation of a broad 3D fan-spine configuration above the emerging bipole. The first reconnection involves emerging fields and a set of large-scale arcade field lines. It results in the launch of a torsional MHD wave that propagates along the arcades, and in the formation of a sheared loop system on one side of the emerging flux. The second reconnection occurs between these newly formed loops and remote arcade fields, and yields the formation of a second loop system on the opposite side of the emerging flux. The two loop systems collectively display an anenome pattern that is located below the fan surface. The flux that surrounds the inner spine field line of the nullpoint retains a fraction of the emerged twist, while the remaining twist is evacuated along the reconnected arcades. The nature and timing of the features which occur in the simulation do qualititatively reproduce those observed by XRT in the particular event studied in this paper. Moreover, the two-step reconnection process suggests a new consistent and generic model for the formation of anemone regions in the solar corona.« less

Operative team communication during simulated emergencies: Too busy to respond?

PubMed

Davis, W Austin; Jones, Seth; Crowell-Kuhnberg, Adrianna M; O'Keeffe, Dara; Boyle, Kelly M; Klainer, Suzanne B; Smink, Douglas S; Yule, Steven

2017-05-01

Ineffective communication among members of a multidisciplinary team is associated with operative error and failure to rescue. We sought to measure operative team communication in a simulated emergency using an established communication framework called "closed loop communication." We hypothesized that communication directed at a specific recipient would be more likely to elicit a check back or closed loop response and that this relationship would vary with changes in patients' clinical status. We used the closed loop communication framework to code retrospectively the communication behavior of 7 operative teams (each comprising 2 surgeons, anesthesiologists, and nurses) during response to a simulated, postanesthesia care unit "code blue." We identified call outs, check backs, and closed loop episodes and applied descriptive statistics and a mixed-effects negative binomial regression to describe characteristics of communication in individuals and in different specialties. We coded a total of 662 call outs. The frequency and type of initiation and receipt of communication events varied between clinical specialties (P < .001). Surgeons and nurses initiated fewer and received more communication events than anesthesiologists. For the average participant, directed communication increased the likelihood of check back by at least 50% (P = .021) in periods preceding acute changes in the clinical setting, and exerted no significant effect in periods after acute changes in the clinical situation. Communication patterns vary by specialty during a simulated operative emergency, and the effect of directed communication in eliciting a response depends on the clinical status of the patient. Operative training programs should emphasize the importance of quality communication in the period immediately after an acute change in the clinical setting of a patient and recognize that communication patterns and needs vary between members of multidisciplinary operative teams. Copyright © 2016 Elsevier Inc. All rights reserved.

Signatures of the impact of flare-ejected plasma on the photosphere of a sunspot light bridge

NASA Astrophysics Data System (ADS)

Felipe, T.; Collados, M.; Khomenko, E.; Rajaguru, S. P.; Franz, M.; Kuckein, C.; Asensio Ramos, A.

2017-12-01

Aims: We investigate the properties of a sunspot light bridge, focusing on the changes produced by the impact of a plasma blob ejected from a C-class flare. Methods: We observed a sunspot in active region NOAA 12544 using spectropolarimetric raster maps of the four Fe I lines around 15 655 Å with the GREGOR Infrared Spectrograph, narrow-band intensity images sampling the Fe I 6173 Å line with the GREGOR Fabry-Pérot Interferometer, and intensity broad-band images in G-band and Ca II H-band with the High-resolution Fast Imager. All these instruments are located at the GREGOR telescope at the Observatorio del Teide, Tenerife, Spain. The data cover the time before, during, and after the flare event. The analysis is complemented with Atmospheric Imaging Assembly and Helioseismic and Magnetic Imager data from the Solar Dynamics Observatory. The physical parameters of the atmosphere at differents heights were inferred using spectral-line inversion techniques. Results: We identify photospheric and chromospheric brightenings, heating events, and changes in the Stokes profiles associated with the flare eruption and the subsequent arrival of the plasma blob to the light bridge, after traveling along an active region loop. Conclusions: The measurements suggest that these phenomena are the result of reconnection events driven by the interaction of the plasma blob with the magnetic field topology of the light bridge. Movies attached to Figs. 1 and 3 are available at http://www.aanda.org

The Statistical Loop Analyzer (SLA)

NASA Technical Reports Server (NTRS)

Lindsey, W. C.

1985-01-01

The statistical loop analyzer (SLA) is designed to automatically measure the acquisition, tracking and frequency stability performance characteristics of symbol synchronizers, code synchronizers, carrier tracking loops, and coherent transponders. Automated phase lock and system level tests can also be made using the SLA. Standard baseband, carrier and spread spectrum modulation techniques can be accomodated. Through the SLA's phase error jitter and cycle slip measurements the acquisition and tracking thresholds of the unit under test are determined; any false phase and frequency lock events are statistically analyzed and reported in the SLA output in probabilistic terms. Automated signal drop out tests can be performed in order to trouble shoot algorithms and evaluate the reacquisition statistics of the unit under test. Cycle slip rates and cycle slip probabilities can be measured using the SLA. These measurements, combined with bit error probability measurements, are all that are needed to fully characterize the acquisition and tracking performance of a digital communication system.

Documentation of programs that compute 1) static tilts for a spatially variable slip distribution, and 2) quasi-static tilts produced by an expanding dislocation loop with a spatially variable slip distribution

USGS Publications Warehouse

McHugh, Stuart

1976-01-01

The material in this report is concerned with the effects of a vertically oriented rectangular dislocation loop on the tilts observed at the free surface of an elastic half-space. Part I examines the effect of a spatially variable static strike-slip distribution across the slip surface. The tilt components as a function of distance parallel, or perpendicular, to the strike of the slip surface are displayed for different slip-versus-distance profiles. Part II examines the effect of spatially and temporally variable slip distributions across the dislocation loop on the quasi-static tilts at the free surface of an elastic half space. The model discussed in part II may be used to generate theoretical tilt versus time curves produced by creep events.

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.

PubMed

Blaha-Nelson, David; Krüger, Dennis M; Szeler, Klaudia; Ben-David, Moshe; Kamerlin, Shina Caroline Lynn

2017-01-25

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k cat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1's active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar "gating loop" or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates.

Speed-Accuracy Trade-Off in Skilled Typewriting: Decomposing the Contributions of Hierarchical Control Loops

ERIC Educational Resources Information Center

Yamaguchi, Motonori; Crump, Matthew J. C.; Logan, Gordon D.

2013-01-01

Typing performance involves hierarchically structured control systems: At the higher level, an outer loop generates a word or a series of words to be typed; at the lower level, an inner loop activates the keystrokes comprising the word in parallel and executes them in the correct order. The present experiments examined contributions of the outer-…

Autoregulatory Characteristics of a Bacillus anthracis Serine/Threonine Kinase▿

PubMed Central

Bryant-Hudson, Katie M.; Shakir, Salika M.; Ballard, Jimmy D.

2011-01-01

BA-Stk1 is a serine/threonine kinase (STK) expressed by Bacillus anthracis. In previous studies, we found that BA-Stk1 activity is modulated through dephosphorylation by a partner phosphatase, BA-Stp1. In this study, we identified critical phosphorylation regions of BA-Stk1 and determined the contributions of these phosphodomains to autophosphorylation and substrate phosphorylation. The data indicate that BA-Stk1 undergoes trans-autophosphorylation within a regulatory domain, referred to as the activation loop, which carries eight putative regulatory serine and threonine residues. We identified activation loop mutants that impacted kinase activity in three different manners: regulation of autophosphorylation (T162), regulation of substrate phosphorylation (T159 and S169), and regulation of overall kinase activity (T163). Tandem mass spectrometry (MS/MS) analysis of the phosphorylation profile of each mutant revealed a second site of phosphorylation on the kinase that was influenced by the phosphorylation status of the activation loop. This second region of the kinase contained a single phosphorylation residue, S214. Previous work has shown S214 to be necessary for downstream substrate phosphorylation, and we have shown that this residue is subject to dephosphorylation by BA-Stp1. These findings indicate a connection between the phosphorylation status of the activation loop and phosphorylation of S214, and this suggests a previously undescribed model for how a bacterial STK shifts from a state of autophosphorylation to targeting downstream substrates. PMID:21296958

Activation of Membrane Fusion by Murine Leukemia Viruses Is Controlled in cis or in trans by Interactions between the Receptor-Binding Domain and a Conserved Disulfide Loop of the Carboxy Terminus of the Surface Glycoprotein

PubMed Central

Lavillette, Dimitri; Boson, Bertrand; Russell, Stephen J.; Cosset, François-Loïc

2001-01-01

Cell entry of retroviruses is initiated by the recognition of cellular receptors and the subsequent membrane fusion between viral and cellular membranes. These two steps are mediated by the surface (SU) and transmembrane (TM) subunits of the retroviral envelope glycoprotein (Env), respectively. Determinants regulating membrane fusion have been described throughout SU and TM, but the processes coupling receptor recognition to fusion are still elusive. Here we establish that a critical interaction is formed between the receptor-binding domain (RBD) and the major disulfide loop of the carboxy-terminal domain (C domain) of the murine leukemia virus SU. Receptor binding causes an alteration of this interaction and, in turn, promotes further events of Env fusion activation. We characterize mutations which, by lowering this interaction and reducing the compatibility between the RBD and C domains of Env glycoprotein chimeras, affect both Env fusogenicity and sensitivity to receptor interference. Additionally, we demonstrate that suboptimal interactions in such mutant Env proteins can be compensated in trans by soluble RBDs in a manner that depends on their compatibility with the C domain. Our results therefore indicate that RBD/C domain interactions may occur in cis, via the proper RBD of the viral Env itself, or in trans, via a distinct RBD expressed by virion-free Env glycoproteins expressed endogenously by the infected cells or provided by neighboring Env trimers. PMID:11264358

Observations of loops and prominences

NASA Technical Reports Server (NTRS)

Strong, Keith T.

1994-01-01

We review recent observations by the Yohkoh-SXT (Soft X-ray Telescope) in collaboration with other spacecraft and ground-based observatories of coronal loops and prominences. These new results point to problems that SoHO will be able to address. With a unique combination of rapid-cadence digital imaging (greater than or equal to 32 s full-disk and greater than or equal to 2 s partial-frame images), high spatial resolution (greater than or equal to 2.5 arcsec pixels), high sensitivity (EM less than or equal to 10(exp 42) cm(exp -3)), a low-scatter mirror, and large dynamic range, SXT can observe a vast range of targets on the Sun. Over the first 21 months of Yohkoh operations SXT has taken over one million images of the corona and so is building up an invaluable long-term database on the large-scale corona and loop geometry. The most striking thing about the SXT images is the range of loop sizes and shapes. The active regions are a bright tangle of magnetic field lines, surrounded by a network of large-scale quiet-Sun loops stretching over distances in excess of 105 km. The cross-section of most loops seems to be constant. Loops displaying significant Gamma's are the exception, not the rule, implying the presence of widespread currents in the corona. All magnetic structures show changes. Time scales range from seconds to months. The question of how these structures are formed, become filled with hot plasma, and are maintained is still open. While we see the propagation of brightenings along the length of active-region loops and in X-ray jets with velocities of several hundred km/s, much higher velocities are seen in the quiet Sun. In XBP flares, for example, velocities of over 1000 km/s are common. Active-region loops seem to be in constant motion, moving slowly outward, carrying plasma with them. During flares, loops often produce localized brightenings at the base and later at the apex of the loop. Quiescent filaments and prominences have been observed regularly. Their coronal manifestation seems to be an extended arcade of loops overlying the filament. Reliable alignment of the ground-based data with the X-ray images make it possible to make a detailed intercomparison of the hot and cold plasma structures over extended periods. Hence we are able to follow the long-term evolution of these structures and see how they become destabilized and erupt.

Temperature and Electron Density Diagnostics of a Candle-Flame Shaped Flare. Asymmetric Reconnection Evidence

NASA Astrophysics Data System (ADS)

Guidoni, Silvina E.; McKenzie, David E.; Longcope, Dana W.; Plowman, Joseph E.; Yoshimura, Keiji

2013-03-01

Candle-flame shaped flares are archetypical structures that represent indirect evidence of magnetic reconnection. For long-lived events, most of their observed features can be explained with the classic magnetic reconnection model of solar flares, the CSHKP model. A flare resembling 1992 Tsuneta's famous candle-flame flare occurred on January 28 2011; we present its temperature and electron density diagnostics. This flare was observed with Hinode/XRT, SDO/AIA, and STEREO (A)/EUVI, resulting in high resolution, broad temperature coverage, and stereoscopic views of this iconic structure. Our XRT filter-ratio temperature and density maps corroborate the general reconnection scenario. The high temperature images reveal a brightening that grows in size to form a tower-like structure at the top of the post-flare arcade, a feature that has been observed in other long duration events. This tower is a localized density increase, as shown by our XRT electron density maps. Despite the extensive work on the standard reconnection scenario, there is no complete agreement among models regarding the nature of this tower-like structure. The XRT maps also reveal that reconnected loops that are successively connected at their tops to this tower develop a density increase in one of their legs that can reach over 2 times the density value of the other leg, giving the appearance of ``half-loops''. Their density is nevertheless still lower than at the tower. These jumps in density last longer than several acoustic transit times along the loops. We use STEREO images to show that the half-loop brightening is not a line-of- sight projection effect of the type suggested by Forbes and Acton (1996). This would indicate that asymmetric reconnection took place between loops originally belonging to systems with different magnetic field strengths, densities, and temperatures. We hypothesize that the heat generated by reconnection's slow shocks is then transferred to each leg of the loop at different rates. Therefore, the increase in electron density due to chromospheric evaporation is different in each leg. Thermal pressure balance between the legs is prevented by shocked plasma at the top of the loops. We also present preliminary results comparing a new fast DEM method that uses SDO/AIA data with the XRT filter ratio method. Both methods complement each other, they agree at the overlap between their instruments' temperature response functions (3-12 MK) while the SDO/AIA method works well at lower temperatures and the XRT one at higher temperatures.

Autonomous navigation system and method

DOEpatents

Bruemmer, David J [Idaho Falls, ID; Few, Douglas A [Idaho Falls, ID

2009-09-08

A robot platform includes perceptors, locomotors, and a system controller, which executes instructions for autonomously navigating a robot. The instructions repeat, on each iteration through an event timing loop, the acts of defining an event horizon based on the robot's current velocity, detecting a range to obstacles around the robot, testing for an event horizon intrusion by determining if any range to the obstacles is within the event horizon, and adjusting rotational and translational velocity of the robot accordingly. If the event horizon intrusion occurs, rotational velocity is modified by a proportion of the current rotational velocity reduced by a proportion of the range to the nearest obstacle and translational velocity is modified by a proportion of the range to the nearest obstacle. If no event horizon intrusion occurs, translational velocity is set as a ratio of a speed factor relative to a maximum speed.

UNRAVELLING THE COMPONENTS OF A MULTI-THERMAL CORONAL LOOP USING MAGNETOHYDRODYNAMIC SEISMOLOGY

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

Prasad, S. Krishna; Jess, D. B.; Klimchuk, J. A.

Coronal loops, constituting the basic building blocks of the active Sun, serve as primary targets to help understand the mechanisms responsible for maintaining multi-million Kelvin temperatures in the solar and stellar coronae. Despite significant advances in observations and theory, our knowledge on the fundamental properties of these structures is limited. Here, we present unprecedented observations of accelerating slow magnetoacoustic waves along a coronal loop that show differential propagation speeds in two distinct temperature channels, revealing the multi-stranded and multithermal nature of the loop. Utilizing the observed speeds and employing nonlinear force-free magnetic field extrapolations, we derive the actual temperature variationmore » along the loop in both channels, and thus are able to resolve two individual components of the multithermal loop for the first time. The obtained positive temperature gradients indicate uniform heating along the loop, rather than isolated footpoint heating.« less

Conserved Loop Cysteines of Vitamin K Epoxide Reductase Complex Subunit 1-like 1 (VKORC1L1) Are Involved in Its Active Site Regeneration*

PubMed Central

Tie, Jian-Ke; Jin, Da-Yun; Stafford, Darrel W.

2014-01-01

Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions. PMID:24532791

Conserved loop cysteines of vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) are involved in its active site regeneration.

PubMed

Tie, Jian-Ke; Jin, Da-Yun; Stafford, Darrel W

2014-03-28

Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions.

Alterations in aerobic energy expenditure and neuromuscular function during a simulated cross-country skiathlon with the skating technique.

PubMed

Fabre, Nicolas; Mourot, Laurent; Zoppirolli, Chiara; Andersson, Erik; Willis, Sarah J; Holmberg, Hans-Christer

2015-04-01

Here, we tested the hypothesis that aerobic energy expenditure (AEE) is higher during a simulated 6-km (2 loops of 3-km each) "skiathlon" than during skating only on a treadmill and attempted to link any such increase to biomechanical and neuromuscular responses. Six elite male cross-country skiers performed two pre-testing time-trials (TT) to determine their best performances and to choose an appropriate submaximal speed for collection of physiological, biomechanical and neuromuscular data during two experimental sessions (exp). Each skier used, in randomized order, either the classical (CL) or skating technique (SK) for the first 3-km loop, followed by transition to the skating technique for the second 3-km loop. Respiratory parameters were recorded continuously. The EMG activity of the triceps brachii (TBr) and vastus lateralis (VLa) muscles during isometric contractions performed when the skiers were stationary (i.e., just before the first loop, during the transition, and after the second loop); their corresponding activity during dynamic contractions; and pole and plantar forces during the second loop were recorded. During the second 3-km of the TT, skating speed was significantly higher for the SK-SK than CL-SK. During this second loop, AEE was also higher (+1.5%) for CL-SKexp than SK-SKexp, in association with higher VLa EMG activity during both isometric and dynamic contractions, despite no differences in plantar or pole forces, poling times or cycle rates. Although the underlying mechanism remains unclear, during a skiathlon, the transition between the sections of classical skiing and skating alters skating performance (i.e., skiing speed), AEE and neuromuscular function. Copyright © 2015 Elsevier B.V. All rights reserved.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions.

PubMed

Tran, Tran T; Kulis, Christina; Long, Steven M; Bryant, Darryn; Adams, Peter; Smythe, Mark L

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions

NASA Astrophysics Data System (ADS)

Tran, Tran T.; Kulis, Christina; Long, Steven M.; Bryant, Darryn; Adams, Peter; Smythe, Mark L.

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Excitation of flare-induced waves in coronal loops and the effects of radiative cooling

NASA Astrophysics Data System (ADS)

Provornikova, Elena; Ofman, Leon; Wang, Tongjiang

2018-01-01

EUV imaging observations from several space missions (SOHO/EIT, TRACE, and SDO/AIA) have revealed a presence of propagating intensity disturbances in solar coronal loops. These disturbances are typically interpreted as slow magnetoacoustic waves. However, recent spectroscopic observations with Hinode/EIS of active region loops revealed that the propagating intensity disturbances are associated with intermittent plasma upflows (or jets) at the footpoints which are presumably generated by magnetic reconnection. For this reason, whether these disturbances are waves or periodic flows is still being studied. This study is aimed at understanding the physical properties of observed disturbances by investigating the excitation of waves by hot plasma injections from below and the evolution of flows and wave propagation along the loop. We expand our previous studies based on isothermal 3D MHD models of an active region to a more realistic model that includes full energy equation accounting for the effects of radiative losses. Computations are initialized with an equilibrium state of a model active region using potential (dipole) magnetic field, gravitationally stratified density and temperature obtained from the polytropic equation of state. We model an impulsive injection of hot plasma into the steady plasma outflow along the loops of different temperatures, warm (∼1 MK) and hot (∼6 MK). The simulations show that hot jets launched at the coronal base excite slow magnetoacoustic waves that propagate to high altitudes along the loops, while the injected hot flows decelerate rapidly with heights. Our results support that propagating disturbances observed in EUV are mainly the wave features. We also find that the effect of radiative cooling on the damping of slow-mode waves in 1-6 MK coronal loops is small, in agreement with the previous conclusion based on 1D MHD models.

On inappropriately used neuronal circuits as a possible basis of the ``loop-swimming'' behaviour of fish under reduced gravity: a theoretical study

NASA Astrophysics Data System (ADS)

Anken, R. H.; Rahmann, H.

One hypothesis for the explanation of the so-called ``loop-swimming'' behaviour in fish when being subjected to reduced gravity assumes that the activities of the differently weighted otoliths of the two labyrinths are well compensated on ground but that a functional asymmetry is induced in weightlessness, resulting in a tonus asymmetry of the body and by this generating the ``loop-swimming'' behaviour. The basis of this abnormal behaviour has to be searched for in the central nervous system (cns), where the signal-transduction from the inner ear- related signal internalisation to the signal response takes place. Circuits within the CNS of fish, that could possibly generate the ``loop-swimming'', might be as follows: An asymmetric activation of vestibulospinal circuits would directly result in a tonus asymmetry of the body. An asymmetric activation of the oculomotor nucleus would generate an asymmetrical rotation of the eyes. This would cause in its turn asymmetric images on the two retinas, which were forwarded to the diencephalic accessory optic system (AOS). It is the task of the AOS to stabilize retinal images, thereby involving the cerebellum, which is the main integration center for sensory and motor modalities. With this, the cerebellar output would generate a tonus asymmetry of the body in order to make the body of the fish follow its eyes. Such movements (especially when assuming an open loop control) would end up in the aforementioned ``loop-swimming'' behaviour.

Simultaneous Solar Maximum Mission (SMM) and Very Large Array (VLA) observations of solar active regions

NASA Technical Reports Server (NTRS)

Willson, Robert F.

1991-01-01

Very Large Array observations at 20 cm wavelength can detect the hot coronal plasma previously observed at soft x ray wavelengths. Thermal cyclotron line emission was detected at the apex of coronal loops where the magnetic field strength is relatively constant. Detailed comparison of simultaneous Solar Maximum Mission (SMM) Satellite and VLA data indicate that physical parameters such as electron temperature, electron density, and magnetic field strength can be obtained, but that some coronal loops remain invisible in either spectral domain. The unprecedent spatial resolution of the VLA at 20 cm wavelength showed that the precursor, impulsive, and post-flare components of solar bursts originate in nearby, but separate loops or systems of loops.. In some cases preburst heating and magnetic changes are observed from loops tens of minutes prior to the impulsive phase. Comparisons with soft x ray images and spectra and with hard x ray data specify the magnetic field strength and emission mechanism of flaring coronal loops. At the longer 91 cm wavelength, the VLA detected extensive emission interpreted as a hot 10(exp 5) K interface between cool, dense H alpha filaments and the surrounding hotter, rarefield corona. Observations at 91 cm also provide evidence for time-correlated bursts in active regions on opposite sides of the solar equator; they are attributed to flare triggering by relativistic particles that move along large-scale, otherwise-invisible, magnetic conduits that link active regions in opposite hemispheres of the Sun.

Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.

PubMed

Hamperl, Stephan; Bocek, Michael J; Saldivar, Joshua C; Swigut, Tomek; Cimprich, Karlene A

2017-08-10

Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

Counterstreaming solar wind halo electron events on open field lines?

NASA Technical Reports Server (NTRS)

Gosling, J. T.; Mccomas, D. J.; Phillips, J. L.

1992-01-01

Counterstreaming solar wind halo electron events have been identified as a common 1 AU signature of coronal mass ejection events, and have generally been interpreted as indicative of closed magnetic field topologies, i.e., magnetic loops or flux ropes rooted at both ends in the Sun, or detached plasmoids. In this paper we examine the possibility that these events may instead occur preferentially on open field lines, and that counterstreaming results from reflection or injection behind interplanetary shocks or from mirroring from regions of compressed magnetic field farther out in the heliosphere. We conclude that neither of these suggested sources of counterstreaming electron beams is viable and that the best interpretation of observed counterstreaming electron events in the solar wind remains that of passage of closed field structures.

Reliable Control Using Disturbance Observer and Equivalent Transfer Function for Position Servo System in Current Feedback Loop Failure

NASA Astrophysics Data System (ADS)

Ishikawa, Kaoru; Nakamura, Taro; Osumi, Hisashi

A reliable control method is proposed for multiple loop control system. After a feedback loop failure, such as case of the sensor break down, the control system becomes unstable and has a big fluctuation even if it has a disturbance observer. To cope with this problem, the proposed method uses an equivalent transfer function (ETF) as active redundancy compensation after the loop failure. The ETF is designed so that it does not change the transfer function of the whole system before and after the loop failure. In this paper, the characteristic of reliable control system that uses an ETF and a disturbance observer is examined by the experiment that uses the DC servo motor for the current feedback loop failure in the position servo system.

Osmotic mechanism of the loop extrusion process

NASA Astrophysics Data System (ADS)

Yamamoto, Tetsuya; Schiessel, Helmut

2017-09-01

The loop extrusion theory assumes that protein factors, such as cohesin rings, act as molecular motors that extrude chromatin loops. However, recent single molecule experiments have shown that cohesin does not show motor activity. To predict the physical mechanism involved in loop extrusion, we here theoretically analyze the dynamics of cohesin rings on a loop, where a cohesin loader is in the middle and unloaders at the ends. Cohesin monomers bind to the loader rather frequently and cohesin dimers bind to this site only occasionally. Our theory predicts that a cohesin dimer extrudes loops by the osmotic pressure of cohesin monomers on the chromatin fiber between the two connected rings. With this mechanism, the frequency of the interactions between chromatin segments depends on the loading and unloading rates of dimers at the corresponding sites.

Hypervelocity gun. [using both electric and chemical energy for projectile propulsion

NASA Technical Reports Server (NTRS)

Ford, F. C.; Biehl, A. J. (Inventor)

1965-01-01

A velocity amplifier system which uses both electric and chemical energy for projectile propulsion is provided in a compact hypervelocity gun suitable for laboratory use. A relatively heavy layer of a tamping material such as concrete encloses a loop of an electrically conductive material. An explosive charge at least partially surrounding the loop is adapted to collapse the loop upon detonation of the charge. A source of electricity charges the loop through two leads, and an electric switch which is activated by the charge explosive charge, disconnects the leads from the source of electricity and short circuits them. An opening in the tamping material extends to the loop and forms a barrel. The loop, necked down in the opening, forms the sabot on which the projectile is located. When the loop is electrically charged and the explosive detonated, the loop is short circuited and collapsed thus building up a magnetic field which acts as a sabot catcher. The sabot is detached from the loop and the sabot and projectile are accelerated to hypervelocity.

Systems-Level Feedbacks of NRF2 Controlling Autophagy upon Oxidative Stress Response

PubMed Central

Kapuy, Orsolya; Papp, Diána; Bánhegyi, Gábor

2018-01-01

Although the primary role of autophagy-dependent cellular self-eating is cytoprotective upon various stress events (such as starvation, oxidative stress, and high temperatures), sustained autophagy might lead to cell death. A transcription factor called NRF2 (nuclear factor erythroid-related factor 2) seems to be essential in maintaining cellular homeostasis in the presence of either reactive oxygen or nitrogen species generated by internal metabolism or external exposure. Accumulating experimental evidence reveals that oxidative stress also influences the balance of the 5′ AMP-activated protein kinase (AMPK)/rapamycin (mammalian kinase target of rapamycin or mTOR) signaling pathway, thereby inducing autophagy. Based on computational modeling here we propose that the regulatory triangle of AMPK, NRF2 and mTOR guaranties a precise oxidative stress response mechanism comprising of autophagy. We suggest that under conditions of oxidative stress, AMPK is crucial for autophagy induction via mTOR down-regulation, while NRF2 fine-tunes the process of autophagy according to the level of oxidative stress. We claim that the cellular oxidative stress response mechanism achieves an incoherently amplified negative feedback loop involving NRF2, mTOR and AMPK. The mTOR-NRF2 double negative feedback generates bistability, supporting the proper separation of two alternative steady states, called autophagy-dependent survival (at low stress) and cell death (at high stress). In addition, an AMPK-mTOR-NRF2 negative feedback loop suggests an oscillatory characteristic of autophagy upon prolonged intermediate levels of oxidative stress, resulting in new rounds of autophagy stimulation until the stress events cannot be dissolved. Our results indicate that AMPK-, NRF2- and mTOR-controlled autophagy induction provides a dynamic adaptation to altering environmental conditions, assuming their new frontier in biomedicine. PMID:29510589

Cbl Associates with Pyk2 and Src to Regulate Src Kinase Activity, αvβ3 Integrin-Mediated Signaling, Cell Adhesion, and Osteoclast Motility

PubMed Central

Sanjay, Archana; Houghton, Adam; Neff, Lynn; DiDomenico, Emilia; Bardelay, Chantal; Antoine, Evelyne; Levy, Joan; Gailit, James; Bowtell, David; Horne, William C.; Baron, Roland

2001-01-01

The signaling events downstream of integrins that regulate cell attachment and motility are only partially understood. Using osteoclasts and transfected 293 cells, we find that a molecular complex comprising Src, Pyk2, and Cbl functions to regulate cell adhesion and motility. The activation of integrin αvβ3 induces the [Ca2+]i-dependent phosphorylation of Pyk2 Y402, its association with Src SH2, Src activation, and the Src SH3-dependent recruitment and phosphorylation of c-Cbl. Furthermore, the PTB domain of Cbl is shown to bind to phosphorylated Tyr-416 in the activation loop of Src, the autophosphorylation site of Src, inhibiting Src kinase activity and integrin-mediated adhesion. Finally, we show that deletion of c Src or c-Cbl leads to a decrease in osteoclast migration. Thus, binding of αvβ3 integrin induces the formation of a Pyk2/Src/Cbl complex in which Cbl is a key regulator of Src kinase activity and of cell adhesion and migration. These findings may explain the osteopetrotic phenotype in the Src−/− mice. PMID:11149930

Three-dimensional characterization of tethered microspheres by total internal reflection fluorescence microscopy

NASA Technical Reports Server (NTRS)

Blumberg, Seth; Gajraj, Arivalagan; Pennington, Matthew W.; Meiners, Jens-Christian

2005-01-01

Tethered particle microscopy is a powerful tool to study the dynamics of DNA molecules and DNA-protein complexes in single-molecule experiments. We demonstrate that stroboscopic total internal reflection microscopy can be used to characterize the three-dimensional spatiotemporal motion of DNA-tethered particles. By calculating characteristic measures such as symmetry and time constants of the motion, well-formed tethers can be distinguished from defective ones for which the motion is dominated by aberrant surface effects. This improves the reliability of measurements on tether dynamics. For instance, in observations of protein-mediated DNA looping, loop formation is distinguished from adsorption and other nonspecific events.

A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes.

PubMed

Rodríguez-Escudero, Isabel; Oliver, María D; Andrés-Pons, Amparo; Molina, María; Cid, Víctor J; Pulido, Rafael

2011-11-01

The PTEN (phosphatase and tensin homolog) phosphatase is unique in mammals in terms of its tumor suppressor activity, exerted by dephosphorylation of the lipid second messenger PIP(3) (phosphatidylinositol 3,4,5-trisphosphate), which activates the phosphoinositide 3-kinase/Akt/mTOR (mammalian target of rapamycin) oncogenic pathway. Loss-of-function mutations in the PTEN gene are frequent in human cancer and in the germline of patients with PTEN hamartoma tumor-related syndromes (PHTSs). In addition, PTEN is mutated in patients with autism spectrum disorders (ASDs), although no functional information on these mutations is available. Here, we report a comprehensive in vivo functional analysis of human PTEN using a heterologous yeast reconstitution system. Ala-scanning mutagenesis at the catalytic loops of PTEN outlined the critical role of residues within the P-catalytic loop for PIP(3) phosphatase activity in vivo. PTEN mutations that mimic the P-catalytic loop of mammalian PTEN-like proteins (TPTE, TPIP, tensins and auxilins) affected PTEN function variably, whereas tumor- or PHTS-associated mutations targeting the PTEN P-loop produced complete loss of function. Conversely, Ala-substitutions, as well as tumor-related mutations at the WPD- and TI-catalytic loops, displayed partial activity in many cases. Interestingly, a tumor-related D92N mutation was partially active, supporting the notion that the PTEN Asp92 residue might not function as the catalytic general acid. The analysis of a panel of ASD-associated hereditary PTEN mutations revealed that most of them did not substantially abrogate PTEN activity in vivo, whereas most of PHTS-associated mutations did. Our findings reveal distinctive functional patterns among PTEN mutations found in tumors and in the germline of PHTS and ASD patients, which could be relevant for therapy.

Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

PubMed

Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A; Brunner, Michael R; Davidson, Iain F; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A; Peters, Jan-Michael

2016-05-10

Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/C(CDC20) activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/C(CDC20) activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/C(CDC20) activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis.

Mechanism of APC/CCDC20 activation by mitotic phosphorylation

PubMed Central

Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G.; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A.; Brunner, Michael R.; Davidson, Iain F.; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A.; Peters, Jan-Michael

2016-01-01

Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/CCDC20 activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/CCDC20 activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/CCDC20 activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis. PMID:27114510

The role of potential vorticity anomalies in the Somali Jet on Indian Summer Monsoon Intraseasonal Variability

NASA Astrophysics Data System (ADS)

Rai, P.; Joshi, M.; Dimri, A. P.; Turner, A. G.

2017-08-01

The climate of the Indian subcontinent is dominated by rainfall arising from the Indian summer monsoon (ISM) during June to September. Intraseasonal variability during the monsoon is characterized by periods of heavy rainfall interspersed by drier periods, known as active and break events respectively. Understanding and predicting such events is of vital importance for forecasting human impacts such as water resources. The Somali Jet is a key regional feature of the monsoon circulation. In the present study, we find that the spatial structure of Somali Jet potential vorticity (PV) anomalies varies considerably during active and break periods. Analysis of these anomalies shows a mechanism whereby sea surface temperature (SST) anomalies propagate north/northwestwards through the Arabian Sea, caused by a positive feedback loop joining anomalies in SST, convection, modification of PV by diabatic heating and mixing in the atmospheric boundary layer, wind-stress curl, and ocean upwelling processes. The feedback mechanism is consistent with observed variability in the coupled ocean-atmosphere system on timescales of approximately 20 days. This research suggests that better understanding and prediction of monsoon intraseasonal variability in the South Asian monsoon may be gained by analysis of the day-to-day dynamical evolution of PV in the Somali Jet.

The role of potential vorticity anomalies in the Somali Jet on Indian Summer Monsoon Intraseasonal Variability

NASA Astrophysics Data System (ADS)

Rai, P.; Joshi, M.; Dimri, A. P.; Turner, A. G.

2018-06-01

The climate of the Indian subcontinent is dominated by rainfall arising from the Indian summer monsoon (ISM) during June to September. Intraseasonal variability during the monsoon is characterized by periods of heavy rainfall interspersed by drier periods, known as active and break events respectively. Understanding and predicting such events is of vital importance for forecasting human impacts such as water resources. The Somali Jet is a key regional feature of the monsoon circulation. In the present study, we find that the spatial structure of Somali Jet potential vorticity (PV) anomalies varies considerably during active and break periods. Analysis of these anomalies shows a mechanism whereby sea surface temperature (SST) anomalies propagate north/northwestwards through the Arabian Sea, caused by a positive feedback loop joining anomalies in SST, convection, modification of PV by diabatic heating and mixing in the atmospheric boundary layer, wind-stress curl, and ocean upwelling processes. The feedback mechanism is consistent with observed variability in the coupled ocean-atmosphere system on timescales of approximately 20 days. This research suggests that better understanding and prediction of monsoon intraseasonal variability in the South Asian monsoon may be gained by analysis of the day-to-day dynamical evolution of PV in the Somali Jet.

Closed-loop control of epileptiform activities in a neural population model using a proportional-derivative controller

NASA Astrophysics Data System (ADS)

Wang, Jun-Song; Wang, Mei-Li; Li, Xiao-Li; Ernst, Niebur

2015-03-01

Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model (NPM). We propose that a proportional-derivative (PD) type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM. Project supported by the National Natural Science Foundation of China (Grant Nos. 61473208, 61025019, and 91132722), ONR MURI N000141010278, and NIH grant R01EY016281.

Relating Alfvén Wave Heating Model to Observations of a Solar Active Region

NASA Astrophysics Data System (ADS)

Yoritomo, J. Y.; Van Ballegooijen, A. A.

2012-12-01

We compared images from the Solar Dynamics Observatory's (SDO) Atmospheric Imaging Assembly (AIA) with simulations of propagating and dissipating Alfvén waves from a three-dimensional magnetohydrodynamic (MHD) model (van Ballegooijen et. al 2011; Asgari-Targhi & van Ballegooijen 2012). The goal was to search for observational evidence of Alfvén waves in the solar corona and understand their role in coronal heating. We looked at one particular active region on the 5th of May 2012. Certain distinct loops in the SDO/AIA observations were selected and expanded. Movies were created from these selections in an attempt to discover transverse motions that may be Alfvén waves. Using a magnetogram of that day and the corresponding synoptic map, a potential field model was created for the active region. Three-dimensional MHD models for several loops in different locations in the active region were created. Each model specifies the temperature, pressure, magnetic field strength, average heating rate, and other parameters along the loop. We find that the heating is intermittent in the loops and reflection occurs at the transition region. For loops at larger and larger height, a point is reached where thermal non-equilibrium occurs. In the center this critical height is much higher than in the periphery of the active region. Lastly, we find that the average heating rate and coronal pressure decrease with increasing height in the corona. This research was supported by an NSF grant for the Smithsonian Astrophysical Observatory (SAO) Solar REU program and a SDO/AIA grant for the Smithsonian Astrophysical Observatory.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

NASA Astrophysics Data System (ADS)

Duan, Aiying; Jiang, Chaowei; Hu, Qiang; Zhang, Huai; Gary, G. Allen; Wu, S. T.; Cao, Jinbin

2017-06-01

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE-MHD-NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from the region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO/AIA. It is found that the CESE-MHD-NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ˜10°. This suggests that the CESE-MHD-NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (˜30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

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

Duan, Aiying; Zhang, Huai; Jiang, Chaowei

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE–MHD–NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from themore » region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO /AIA. It is found that the CESE–MHD–NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ∼10°. This suggests that the CESE–MHD–NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (∼30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.« less

Low Speed and High Speed Correlation of SMART Active Flap Rotor Loads

NASA Technical Reports Server (NTRS)

Kottapalli, Sesi B. R.

2010-01-01

Measured, open loop and closed loop data from the SMART rotor test in the NASA Ames 40- by 80- Foot Wind Tunnel are compared with CAMRAD II calculations. One open loop high-speed case and four closed loop cases are considered. The closed loop cases include three high-speed cases and one low-speed case. Two of these high-speed cases include a 2 deg flap deflection at 5P case and a test maximum-airspeed case. This study follows a recent, open loop correlation effort that used a simple correction factor for the airfoil pitching moment Mach number. Compared to the earlier effort, the current open loop study considers more fundamental corrections based on advancing blade aerodynamic conditions. The airfoil tables themselves have been studied. Selected modifications to the HH-06 section flap airfoil pitching moment table are implemented. For the closed loop condition, the effect of the flap actuator is modeled by increased flap hinge stiffness. Overall, the open loop correlation is reasonable, thus confirming the basic correctness of the current semi-empirical modifications; the closed loop correlation is also reasonable considering that the current flap model is a first generation model. Detailed correlation results are given in the paper.

Mapping the Structural and Dynamical Features of Multiple p53 DNA Binding Domains: Insights into Loop 1 Intrinsic Dynamics

PubMed Central

Lukman, Suryani; Lane, David P.; Verma, Chandra S.

2013-01-01

The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD). In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs). Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3). Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart). Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1) a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2) possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site. PMID:24324553

Dynamical behaviour in coronal loops

NASA Technical Reports Server (NTRS)

Haisch, Bernhard M.

1986-01-01

Rapid variability has been found in two active region coronal loops observed by the X-ray Polychromator (XRP) and the Hard X-ray Imaging Spectrometer (HXIS) onboard the Solar Maximum Mission (SMM). There appear to be surprisingly few observations of the short-time scale behavior of hot loops, and the evidence presented herein lends support to the hypothesis that coronal heating may be impulsive and driven by flaring.

Dynamical behaviour in coronal loops

NASA Astrophysics Data System (ADS)

Haisch, Bernhard M.

Rapid variability has been found in two active region coronal loops observed by the X-ray Polychromator (XRP) and the Hard X-ray Imaging Spectrometer (HXIS) onboard the Solar Maximum Mission (SMM). There appear to be surprisingly few observations of the short-time scale behavior of hot loops, and the evidence presented herein lends support to the hypothesis that coronal heating may be impulsive and driven by flaring.

Adaptively Adjusted Event-Triggering Mechanism on Fault Detection for Networked Control Systems.

PubMed

Wang, Yu-Long; Lim, Cheng-Chew; Shi, Peng

2016-12-08

This paper studies the problem of adaptively adjusted event-triggering mechanism-based fault detection for a class of discrete-time networked control system (NCS) with applications to aircraft dynamics. By taking into account the fault occurrence detection progress and the fault occurrence probability, and introducing an adaptively adjusted event-triggering parameter, a novel event-triggering mechanism is proposed to achieve the efficient utilization of the communication network bandwidth. Both the sensor-to-control station and the control station-to-actuator network-induced delays are taken into account. The event-triggered sensor and the event-triggered control station are utilized simultaneously to establish new network-based closed-loop models for the NCS subject to faults. Based on the established models, the event-triggered simultaneous design of fault detection filter (FDF) and controller is presented. A new algorithm for handling the adaptively adjusted event-triggering parameter is proposed. Performance analysis verifies the effectiveness of the adaptively adjusted event-triggering mechanism, and the simultaneous design of FDF and controller.

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

PubMed Central

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

2014-01-01

Substrate binding, product release, and likely chemical catalysis in the tryptophan biosynthetic enzyme indole-3-glycerol phosphate synthase (IGPS) are dependent on the structural dynamics of the β1α1 active-site loop. Statistical coupling analysis and molecular dynamic simulations had previously indicated that covarying residues in the β1α1 and β2α2 loops, corresponding to Arg54 and Asn90, respectively, in the Sulfolobus sulfataricus enzyme (ssIGPS), are likely important for coordinating functional motions of these loops. To test this hypothesis, we characterized site mutants at these positions for changes in catalytic function, protein stability and structural dynamics for the thermophilic ssIGPS enzyme. Although there were only modest changes in the overall steady-state kinetic parameters, solvent viscosity and solvent deuterium kinetic isotope effects indicated that these amino acid substitutions change the identity of the rate-determining step across multiple temperatures. Surprisingly, the N90A substitution had a dramatic effect on the general acid/base catalysis of the dehydration step, as indicated by the loss of the descending limb in the pH rate profile, which we had previously assigned to Lys53 on the β1α1 loop. These changes in enzyme function are accompanied with a quenching of ps-ns and µs-ms timescale motions in the β1α1 loop as measured by nuclear magnetic resonance studies. Altogether, our studies provide structural, dynamic and functional rationales for the coevolution of residues on the β1α1 and β2α2 loops, and highlight the multiple roles that the β1α1 loop plays in IGPS catalysis. Thus, substitution of covarying residues in the active-site β1α1 and β2α2 loops of indole-3-glycerol phosphate synthase results in functional, structural, and dynamic changes, highlighting the multiple roles that the β1α1 loop plays in enzyme catalysis and the importance of regulating the structural dynamics of this loop through noncovalent interactions with nearby structural elements. PMID:24403092

Chemical-Looping Combustion and Gasification of Coals and Oxygen Carrier Development: A Brief Review

DOE PAGES

Wang, Ping; Means, Nicholas; Shekhawat, Dushyant; ...

2015-09-24

Chemical-looping technology is one of the promising CO 2 capture technologies. It generates a CO 2 enriched flue gas, which will greatly benefit CO 2 capture, utilization or sequestration. Both chemical-looping combustion (CLC) and chemical-looping gasification (CLG) have the potential to be used to generate power, chemicals, and liquid fuels. Chemical-looping is an oxygen transporting process using oxygen carriers. Recently, attention has focused on solid fuels such as coal. Coal chemical-looping reactions are more complicated than gaseous fuels due to coal properties (like mineral matter) and the complex reaction pathways involving solid fuels. The mineral matter/ash and sulfur in coalmore » may affect the activity of oxygen carriers. Oxygen carriers are the key issue in chemical-looping processes. Thermogravimetric analysis (TGA) has been widely used for the development of oxygen carriers (e.g., oxide reactivity). Two proposed processes for the CLC of solid fuels are in-situ Gasification Chemical-Looping Combustion (iG-CLC) and Chemical-Looping with Oxygen Uncoupling (CLOU). The objectives of this review are to discuss various chemical-looping processes with coal, summarize TGA applications in oxygen carrier development, and outline the major challenges associated with coal chemical-looping in iG-CLC and CLOU.« less

Open-Loop Pitch Table Optimization for the Maximum Dynamic Pressure Orion Abort Flight Test

NASA Technical Reports Server (NTRS)

Stillwater, Ryan A.

2009-01-01

NASA has scheduled the retirement of the space shuttle orbiter fleet at the end of 2010. The Constellation program was created to develop the next generation of human spaceflight vehicles and launch vehicles, known as Orion and Ares respectively. The Orion vehicle is a return to the capsule configuration that was used in the Mercury, Gemini, and Apollo programs. This configuration allows for the inclusion of an abort system that safely removes the capsule from the booster in the event of a failure on launch. The Flight Test Office at NASA's Dryden Flight Research Center has been tasked with the flight testing of the abort system to ensure proper functionality and safety. The abort system will be tested in various scenarios to approximate the conditions encountered during an actual Orion launch. Every abort will have a closed-loop controller with an open-loop backup that will direct the vehicle during the abort. In order to provide the best fit for the desired total angle of attack profile with the open-loop pitch table, the table is tuned using simulated abort trajectories. A pitch table optimization program was created to tune the trajectories in an automated fashion. The program development was divided into three phases. Phase 1 used only the simulated nominal run to tune the open-loop pitch table. Phase 2 used the simulated nominal and three simulated off nominal runs to tune the open-loop pitch table. Phase 3 used the simulated nominal and sixteen simulated off nominal runs to tune the open-loop pitch table. The optimization program allowed for a quicker and more accurate fit to the desired profile as well as allowing for expanded resolution of the pitch table.

VRILLE Controls PDF Neuropeptide Accumulation and Arborization Rhythms in Small Ventrolateral Neurons to Drive Rhythmic Behavior in Drosophila.

PubMed

Gunawardhana, Kushan L; Hardin, Paul E

2017-11-20

In Drosophila, the circadian clock is comprised of transcriptional feedback loops that control rhythmic gene expression responsible for daily rhythms in physiology, metabolism, and behavior. The core feedback loop, which employs CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors to drive rhythmic transcription peaking at dusk, is required for circadian timekeeping and overt behavioral rhythms. CLK-CYC also activates an interlocked feedback loop, which uses the PAR DOMAIN PROTEIN 1ε (PDP1ε) activator and the VRILLE (VRI) repressor to drive rhythmic transcription peaking at dawn. Although Pdp1ε mutants disrupt activity rhythms without eliminating clock function, whether vri is required for clock function and/or output is not known. Using a conditionally inactivatable transgene to rescue vri developmental lethality, we show that clock function persists after vri inactivation but that activity rhythms are abolished. The inactivation of vri disrupts multiple output pathways thought to be important for activity rhythms, including PDF accumulation and arborization rhythms in the small ventrolateral neuron (sLN v ) dorsal projection. These results demonstrate that vri acts as a key regulator of clock output and suggest that the primary function of the interlocked feedback loop in Drosophila is to drive rhythmic transcription required for overt rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

The solution structure of the prototype foamy virus RNase H domain indicates an important role of the basic loop in substrate binding.

PubMed

Leo, Berit; Schweimer, Kristian; Rösch, Paul; Hartl, Maximilian J; Wöhrl, Birgitta M

2012-09-10

The ribonuclease H (RNase H) domains of retroviral reverse transcriptases play an essential role in the replication cycle of retroviruses. During reverse transcription of the viral genomic RNA, an RNA/DNA hybrid is created whose RNA strand needs to be hydrolyzed by the RNase H to enable synthesis of the second DNA strand by the DNA polymerase function of the reverse transcriptase. Here, we report the solution structure of the separately purified RNase H domain from prototype foamy virus (PFV) revealing the so-called C-helix and the adjacent basic loop, which both were suggested to be important in substrate binding and activity. The solution structure of PFV RNase H shows that it contains a mixed five-stranded β-sheet, which is sandwiched by four α-helices (A-D), including the C-helix, on one side and one α-helix (helix E) on the opposite side. NMR titration experiments demonstrate that upon substrate addition signal changes can be detected predominantly in the basic loop as well as in the C-helix. All these regions are oriented towards the bound substrate. In addition, signal intensities corresponding to residues in the B-helix and the active site decrease, while only minor or no changes of the overall structure of the RNase H are detectable upon substrate binding. Dynamic studies confirm the monomeric state of the RNase H domain. Structure comparisons with HIV-1 RNase H, which lacks the basic protrusion, indicate that the basic loop is relevant for substrate interaction, while the C-helix appears to fulfill mainly structural functions, i.e. positioning the basic loop in the correct orientation for substrate binding. The structural data of PFV RNase H demonstrate the importance of the basic loop, which contains four positively charged lysines, in substrate binding and the function of the C-helix in positioning of the loop. In the dimeric full length HIV-1 RT, the function of the basic loop is carried out by a different loop, which also harbors basic residues, derived from the connection domain of the p66 subunit. Our results suggest that RNases H which are also active as separate domains might need a functional basic loop for proper substrate binding.

Active Noise Control of Radiated Noise from Jets Originating NASA

NASA Technical Reports Server (NTRS)

Doty, Michael J.; Fuller, Christopher R.; Schiller, Noah H.; Turner, Travis L.

2013-01-01

The reduction of jet noise using a closed-loop active noise control system with highbandwidth active chevrons was investigated. The high frequency energy introduced by piezoelectrically-driven chevrons was demonstrated to achieve a broadband reduction of jet noise, presumably due to the suppression of large-scale turbulence. For a nozzle with one active chevron, benefits of up to 0.8 dB overall sound pressure level (OASPL) were observed compared to a static chevron nozzle near the maximum noise emission angle, and benefits of up to 1.9 dB OASPL were observed compared to a baseline nozzle with no chevrons. The closed-loop actuation system was able to effectively reduce noise at select frequencies by 1-3 dB. However, integrated OASPL did not indicate further reduction beyond the open-loop benefits, most likely due to the preliminary controller design, which was focused on narrowband performance.

Crystal structure of the unactivated ribulose 1,5-bisphosphate carboxylase/oxygenase complexed with a transition state analog, 2-carboxy-D-arabinitol 1,5-bisphosphate.

PubMed Central

Zhang, K. Y.; Cascio, D.; Eisenberg, D.

1994-01-01

The crystal structure of unactivated ribulose 1,5-bisphosphate carboxylase/oxygenase from Nicotiana tabacum complexed with a transition state analog, 2-carboxy-D-arabinitol 1,5-bisphosphate, was determined to 2.7 A resolution by X-ray crystallography. The transition state analog binds at the active site in an extended conformation. As compared to the binding of the same analog in the activated enzyme, the analog binds in a reverse orientation. The active site Lys 201 is within hydrogen bonding distance of the carboxyl oxygen of the analog. Loop 6 (residues 330-339) remains open and flexible upon binding of the analog in the unactivated enzyme, in contrast to the closed and ordered loop 6 in the activated enzyme complex. The transition state analog is exposed to solvent due to the open conformation of loop 6. PMID:8142899

Characterization of a native hammerhead ribozyme derived from schistosomes

PubMed Central

OSBORNE, EDITH M.; SCHAAK, JANELL E.; DEROSE, VICTORIA J.

2005-01-01

A recent re-examination of the role of the helices surrounding the conserved core of the hammerhead ribozyme has identified putative loop–loop interactions between stems I and II in native hammerhead sequences. These extended hammerhead sequences are more active at low concentrations of divalent cations than are minimal hammerheads. The loop–loop interactions are proposed to stabilize a more active conformation of the conserved core. Here, a kinetic and thermodynamic characterization of an extended hammerhead sequence derived from Schistosoma mansoni is performed. Biphasic kinetics are observed, suggesting the presence of at least two conformers, one cleaving with a fast rate and the other with a slow rate. Replacing loop II with a poly(U) sequence designed to eliminate the interaction between the two loops results in greatly diminished activity, suggesting that the loop–loop interactions do aid in forming a more active conformation. Previous studies with minimal hammerheads have shown deleterious effects of Rp-phosphorothioate substitutions at the cleavage site and 5′ to A9, both of which could be rescued with Cd2+. Here, phosphorothioate modifications at the cleavage site and 5′ to A9 were made in the schistosome-derived sequence. In Mg2+, both phosphorothioate substitutions decreased the overall fraction cleaved without significantly affecting the observed rate of cleavage. The addition of Cd2+ rescued cleavage in both cases, suggesting that these are still putative metal binding sites in this native sequence. PMID:15659358

Status of E-ELT M5 scale-one demonstrator

NASA Astrophysics Data System (ADS)

Barriga, Pablo; Sedghi, Babak; Dimmler, Martin; Kornweibel, Nick

2014-07-01

The fifth mirror of the European Extremely Large Telescope optical train is a field stabilization tip/tilt unit responsible for correcting the dynamical tip and tilt caused mainly by wind load on the telescope. A scale-one prototype including the inclined support, the fixed frame and a basic control system was designed and manufactured by NTE-SENER (Spain) and CSEM (Switzerland) as part of the prototyping and design activities. All interfaces to the mirror have been reproduced on a dummy structure reproducing the inertial characteristics of the optical element. The M5 unit is required to have sufficient bandwidth for tip/tilt reference commands coming from the wavefront control system. Such a bandwidth can be achieved using local active damping loop to damp the low frequency mechanical modes before closing a position loop. Prototyping on the M5 unit has been undertaken in order to demonstrate the E-ELT control system architecture, concepts and development standards and to further study active damping strategies. The control system consists of two nested loops: a local damping loop and a position loop. The development of this control system was undertaken following the E-ELT control system development standards in order to determine their applicability and performance and includes hardware selection, communication, synchronization, configuration, and data logging. In this paper we present the current status of the prototype M5 control system and the latest results on the active damping control strategy, in particular the promising results obtained with the method of positive position feedback.

Modification of "Pressed" Atmospheres in Active Regions of Ultracool Stars

NASA Astrophysics Data System (ADS)

Zaitsev, V. V.; Kronshtadtov, P. V.; Stepanov, A. V.

2017-12-01

Ultracool stars usually have active regions, which is confirmed by their high-power radiofrequency emission modulated by the star axial rotation. The interpretation of this emission is commonly based on the electron cyclotron maser mechanism realized in the active regions. A plasma mechanism of radiofrequency emission is not considered, because ultracool star atmospheres are tightly "pressed" against the star surface, and the plasma frequency is much lower than the electron gyrofrequency ( f L ≪ f B) at the coronal levels. This paper explores active regions of ultracool stars for the possible existence of a system of coronal magnetic loops carrying electric current generated by photospheric convection. It is shown that current dissipation induces a temperature increase inside the loops to about 107 K, which causes an increase in the scale of height of the inhomogeneous atmosphere and, at the coronal levels, effectuates condition f L ≫ f B, at which the plasma mechanism of radiofrequency emission prevails over the electron cyclotron maser mechanism. The magnetic loop parameters, intensity of electric currents generated by the photospheric convection, and efficiency of plasma heating inside the magnetic loops are evaluated on the example of the brown dwarf TVLM513-46546. The scale of the height of the modified atmosphere, which appears to be comparable to the star radius, is calculated; it is shown that the soft X-ray flow created by the hot modified atmosphere inside a coronal magnetic loop is about equal to that observed for brown dwarf TVLM513-46546.

[Development of medical supplies management system].

PubMed

Zhong, Jianping; Shen, Beijun; Zhu, Huili

2012-11-01

This paper adopts advanced information technology to manage medical supplies, in order to improve the medical supplies management level and reduce material cost. It develops a Medical Supplies Management System with B/S and C/S mixed structure, optimizing material management process, building large equipment performance evaluation model, providing interface solution with HIS, and realizing real-time information briefing of high value material's consumption. The medical materials are managed during its full life-cycle. The material consumption of the clinical departments is monitored real-timely. Through the closed-loop management with pre-event budget, mid-event control and after-event analysis, it realizes the final purpose of management yielding benefit.

Method for distributed agent-based non-expert simulation of manufacturing process behavior

DOEpatents

Ivezic, Nenad; Potok, Thomas E.

2004-11-30

A method for distributed agent based non-expert simulation of manufacturing process behavior on a single-processor computer comprises the steps of: object modeling a manufacturing technique having a plurality of processes; associating a distributed agent with each the process; and, programming each the agent to respond to discrete events corresponding to the manufacturing technique, wherein each discrete event triggers a programmed response. The method can further comprise the step of transmitting the discrete events to each agent in a message loop. In addition, the programming step comprises the step of conditioning each agent to respond to a discrete event selected from the group consisting of a clock tick message, a resources received message, and a request for output production message.

Analytical design and evaluation of an active control system for helicopter vibration reduction and gust response alleviation

NASA Technical Reports Server (NTRS)

Taylor, R. B.; Zwicke, P. E.; Gold, P.; Miao, W.

1980-01-01

An analytical study was conducted to define the basic configuration of an active control system for helicopter vibration and gust response alleviation. The study culminated in a control system design which has two separate systems: narrow band loop for vibration reduction and wider band loop for gust response alleviation. The narrow band vibration loop utilizes the standard swashplate control configuration to input controller for the vibration loop is based on adaptive optimal control theory and is designed to adapt to any flight condition including maneuvers and transients. The prime characteristics of the vibration control system is its real time capability. The gust alleviation control system studied consists of optimal sampled data feedback gains together with an optimal one-step-ahead prediction. The prediction permits the estimation of the gust disturbance which can then be used to minimize the gust effects on the helicopter.

Pressure wave charged repetitively pulsed gas laser

DOEpatents

Kulkarny, Vijay A.

1982-01-01

A repetitively pulsed gas laser in which a system of mechanical shutters bracketing the laser cavity manipulate pressure waves resulting from residual energy in the cavity gas following a lasing event so as to draw fresh gas into the cavity and effectively pump spent gas in a dynamic closed loop.

Molecular insights into the mechanism of thermal stability of actinomycete mannanase.

PubMed

Kumagai, Yuya; Uraji, Misugi; Wan, Kun; Okuyama, Masayuki; Kimura, Atsuo; Hatanaka, Tadashi

2016-09-01

Streptomyces thermolilacinus mannanase (StMan), which requires Ca(2+) for its enhanced thermal stability and hydrolysis activity, possesses two Ca(2+) -binding sites in loop6 and loop7. We evaluated the function of the Ca(2+) -binding site in loop7 and the hydrogen bond between residues Ser247 in loop6 and Asp279 in loop7. The Ca(2+) -binding in loop7 was involved only in thermal stability. Mutations of Ser247 or Asp279 retained the Ca(2+) -binding ability; however, mutants showed less thermal stability than StMan. Phylogenetic analysis indicated that most glycoside hydrolase family 5 subfamily 8 mannanases could be stabilized by Ca(2+) ; however, the mechanism of StMan thermal stability was found to be quite specific in some actinomycete mannanases. © 2016 Federation of European Biochemical Societies.

The interdependence of the Rho GTPases and apicobasal cell polarity.

PubMed

Mack, Natalie Ann; Georgiou, Marios

2014-01-01

Signaling via the Rho GTPases provides crucial regulation of numerous cell polarization events, including apicobasal (AB) polarity, polarized cell migration, polarized cell division and neuronal polarity. Here we review the relationships between the Rho family GTPases and epithelial AB polarization events, focusing on the 3 best-characterized members: Rho, Rac and Cdc42. We discuss a multitude of processes that are important for AB polarization, including lumen formation, apical membrane specification, cell-cell junction assembly and maintenance, as well as tissue polarity. Our discussions aim to highlight the immensely complex regulatory mechanisms that encompass Rho GTPase signaling during AB polarization. More specifically, in this review we discuss several emerging common themes, that include: 1) the need for Rho GTPase activities to be carefully balanced in both a spatial and temporal manner through a multitude of mechanisms; 2) the existence of signaling feedback loops and crosstalk to create robust cellular responses; and 3) the frequent multifunctionality that exists among AB polarity regulators. Regarding this latter theme, we provide further discussion of the potential plasticity of the cell polarity machinery and as a result the possible implications for human disease.

The Sustainability Cycle and Loop: models for a more unified understanding of sustainability.

PubMed

Hay, Laura; Duffy, Alex; Whitfield, R I

2014-01-15

In spite of the considerable research on sustainability, reports suggest that we are barely any closer to a more sustainable society. As such, there is an urgent need to improve the effectiveness of human efforts towards sustainability. A clearer and more unified understanding of sustainability among different people and sectors could help to facilitate this. This paper presents the results of an inductive literature investigation, aiming to develop models to explain the nature of sustainability in the Earth system, and how humans can effectively strive for it. The major contributions are two general and complementary models, that may be applied in any context to provide a common basis for understanding sustainability: the Sustainability Cycle (S-Cycle), and the Sustainability Loop (S-Loop). Literature spanning multiple sectors is examined from the perspective of three concepts, emerging as significant in relation to our aim. Systems are shown to provide the context for human action towards sustainability, and the nature of the Earth system and its sub-systems is explored. Activities are outlined as a fundamental target that humans need to sustain, since they produce the entities both needed and desired by society. The basic behaviour of activities operating in the Earth system is outlined. Finally, knowledge is positioned as the driver of human action towards sustainability, and the key components of knowledge involved are examined. The S-Cycle and S-Loop models are developed via a process of induction from the reviewed literature. The S-Cycle describes the operation of activities in a system from the perspective of sustainability. The sustainability of activities in a system depends upon the availability of resources, and the availability of resources depends upon the rate that activities consume and produce them. Humans may intervene in these dynamics via an iterative process of interpretation and action, described in the S-Loop model. The models are briefly applied to a system described in the literature. It is shown that the S-Loop may be used to guide efforts towards sustainability in a particular system of interest, by prescribing the basic activities involved. The S-Cycle may be applied complementary to the S-Loop, to support the interpretation of activity behaviour described in the latter. Given their general nature, the models provide the basis for a more unified understanding of sustainability. It is hoped that their use may go some way towards improving the effectiveness of human action towards sustainability. Copyright © 2013 Elsevier Ltd. All rights reserved.

RELAP5/MOD2 analysis of a postulated cold leg SBLOCA'' simultaneous to a total black-out'' event in the Jose Cabrera Nuclear Station

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

Rebollo, L.

1992-04-01

Several beyond-design bases cold leg small-break LOCA postulated scenarios based on the lessons learned'' in the OECD-LOFT LP-SB-3 experiment have been analyzed for the Westinghouse single loop Jose Cabrera Nuclear Power Plant belonging to the Spanish utility UNION ELECTRICA FENOSA, S.A. The analysis has been done by the utility in the Thermal-Hydraulic Accident Analysis Section of the Engineering Department of the Nuclear Division. The RELAP5/MOD2/36.04 code has been used on a CYBER 180/830 computer and the simulation includes the 6 in. RHRS charging line, the 2 in. pressurizer spray, and the 1.5 in. CVCS make-up line piping breaks. The assumptionmore » of a total black-out condition'' coincident with the occurrence of the event has been made in order to consider a plant degraded condition with total active failure of the ECCS. As a result of the analysis, estimates of the time to core overheating startup'' as well as an evaluation of alternate operator measures to mitigate the consequences of the event have been obtained. Finally a proposal for improving the LOCA emergency operating procedure (E-1) has been suggested.« less

RELAP5/MOD2 analysis of a postulated ``cold leg SBLOCA`` simultaneous to a ``total black-out`` event in the Jose Cabrera Nuclear Station

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

Rebollo, L.

1992-04-01

Several beyond-design bases cold leg small-break LOCA postulated scenarios based on the ``lessons learned`` in the OECD-LOFT LP-SB-3 experiment have been analyzed for the Westinghouse single loop Jose Cabrera Nuclear Power Plant belonging to the Spanish utility UNION ELECTRICA FENOSA, S.A. The analysis has been done by the utility in the Thermal-Hydraulic & Accident Analysis Section of the Engineering Department of the Nuclear Division. The RELAP5/MOD2/36.04 code has been used on a CYBER 180/830 computer and the simulation includes the 6 in. RHRS charging line, the 2 in. pressurizer spray, and the 1.5 in. CVCS make-up line piping breaks. Themore » assumption of a ``total black-out condition`` coincident with the occurrence of the event has been made in order to consider a plant degraded condition with total active failure of the ECCS. As a result of the analysis, estimates of the ``time to core overheating startup`` as well as an evaluation of alternate operator measures to mitigate the consequences of the event have been obtained. Finally a proposal for improving the LOCA emergency operating procedure (E-1) has been suggested.« less

Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

PubMed

Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

2015-11-12

Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis

PubMed Central

Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

2015-01-01

Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis. PMID:26559755

Genetic analysis of the relationship between activation loop phosphorylation and cyclin binding in the activation of the Saccharomyces cerevisiae Cdc28p cyclin-dependent kinase.

PubMed Central

Cross, F R; Levine, K

2000-01-01

We showed recently that a screen for mutant CDC28 with improved binding to a defective Cln2p G1 cyclin yielded a spectrum of mutations similar to those yielded by a screen for intragenic suppressors of the requirement for activation loop phosphorylation (T169E suppressors). Recombination among these mutations yielded CDC28 mutants that bypassed the G1 cyclin requirement. Here we analyze further the interrelationship between T169E suppression, interaction with defective cyclin, and G1 cyclin bypass. DNA shuffling of mutations from the various screens and recombination onto a T169E-encoding 3' end yielded CDC28 mutants with strong T169E suppression. Some of the strongest T169E suppressors could suppress the defective Cln2p G1 cyclin even while retaining T169E. The strong T169E suppressors did not exhibit bypass of the G1 cyclin requirement but did so when T169E was reverted to T. These results suggested that for these mutants, activation loop phosphorylation and cyclin binding might be alternative means of activation rather than independent requirements for activation (as with wild type). These results suggest mechanistic overlap between the conformational shift induced by cyclin binding and that induced by activation loop phosphorylation. This conclusion was supported by analysis of suppressors of a mutation in the Cdk phosphothreonine-binding pocket created by cyclin binding. PMID:10747052

Hydrophobic interaction between the SH2 domain and the kinase domain is required for the activation of Csk.

PubMed

Mikkola, Esa T; Gahmberg, Carl G

2010-06-18

The protein tyrosine kinase C-terminal Src kinase (Csk) is activated by the engagement of its Src homology (SH) 2 domain. However, the molecular mechanism required for this is not completely understood. The crystal structure of the active Csk indicates that Csk could be activated by contact between the SH2 domain and the beta3-alphaC loop in the N-terminal lobe of the kinase domain. To study the importance of this interaction for the SH2-domain-mediated activation of Csk, we mutated the amino acid residues forming the contacts between the SH2 domain and the beta3-alphaC loop. The mutation of the beta3-alphaC loop Ala228 to glycine and of the SH2 domain Tyr116, Tyr133, Leu138, and Leu149 to alanine resulted in the inability of the SH2 domain ligand to activate Csk. Furthermore, the overexpressed Csk mutants A228G, Y133A/Y116A, L138A, and L149A were unable to efficiently inactivate endogenous Src in human embryonic kidney 293 cells. The results suggest that the SH2-domain-mediated activation of Csk is dependent on the binding of the beta3-alphaC loop Ala228 to the hydrophobic pocket formed by the side chains of Tyr116, Tyr133, Leu138, and Leu149 on the surface of the SH2 domain. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Efficient Ligation of the Schistosoma Hammerhead Ribozyme †

PubMed Central

Canny, Marella D.; Jucker, Fiona M.; Pardi, Arthur

2011-01-01

The hammerhead ribozyme from Schistosoma mansoni is the best characterized of the natural hammerhead ribozymes. Biophysical, biochemical, and structural studies have shown that the formation of the loop-loop tertiary interaction between stems I and II alters the global folding, cleavage kinetics, and conformation of the catalytic core of this hammerhead, leading to a ribozyme that is readily cleaved under physiological conditions. This study investigates the ligation kinetics and the internal equilibrium between cleavage and ligation for the Schistosoma hammerhead. Single turnover kinetic studies on a construct where the ribozyme cleaves and ligates substrate(s) in trans showed up to 23% ligation when starting from fully cleaved products. This was achieved by a ~2,000-fold increase in the rate of ligation compared to a minimal hammerhead without the loop-loop tertiary interaction, yielding an internal equilibrium that ranges from 2–3 at physiological Mg2+ ion concentrations (0.1 –1 mM). Thus, the natural Schistosoma hammerhead ribozyme is almost as efficient at ligation as it is at cleavage. The results here are consistent with a model where formation of the loop-loop tertiary interaction leads to a higher population of catalytically active molecules, and where formation of this tertiary interaction has a much larger effect on the ligation than the cleavage activity of the Schistosoma hammerhead ribozyme. PMID:17319693

Crystal structure analysis, covalent docking, and molecular dynamics calculations reveal a conformational switch in PhaZ7 PHB depolymerase.

PubMed

Kellici, Tahsin F; Mavromoustakos, Thomas; Jendrossek, Dieter; Papageorgiou, Anastassios C

2017-07-01

An open and a closed conformation of a surface loop in PhaZ7 extracellular poly(3-hydroxybutyrate) depolymerase were identified in two high-resolution crystal structures of a PhaZ7 Y105E mutant. Molecular dynamics (MD) simulations revealed high root mean square fluctuations (RMSF) of the 281-295 loop, in particular at residue Asp289 (RMSF 7.62 Å). Covalent docking between a 3-hydroxybutyric acid trimer and the catalytic residue Ser136 showed that the binding energy of the substrate is significantly more favorable in the open loop conformation compared to that in the closed loop conformation. MD simulations with the substrate covalently bound depicted 1 Å RMSF higher values for the residues 281-295 in comparison to the apo (substrate-free) form. In addition, the presence of the substrate in the active site enhanced the ability of the loop to adopt a closed form. Taken together, the analysis suggests that the flexible loop 281-295 of PhaZ7 depolymerase can act as a lid domain to control substrate access to the active site of the enzyme. Proteins 2017; 85:1351-1361. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Relaxation oscillations and hierarchy of feedbacks in MAPK signaling

NASA Astrophysics Data System (ADS)

Kochańczyk, Marek; Kocieniewski, Paweł; Kozłowska, Emilia; Jaruszewicz-Błońska, Joanna; Sparta, Breanne; Pargett, Michael; Albeck, John G.; Hlavacek, William S.; Lipniacki, Tomasz

2017-01-01

We formulated a computational model for a MAPK signaling cascade downstream of the EGF receptor to investigate how interlinked positive and negative feedback loops process EGF signals into ERK pulses of constant amplitude but dose-dependent duration and frequency. A positive feedback loop involving RAS and SOS, which leads to bistability and allows for switch-like responses to inputs, is nested within a negative feedback loop that encompasses RAS and RAF, MEK, and ERK that inhibits SOS via phosphorylation. This negative feedback, operating on a longer time scale, changes switch-like behavior into oscillations having a period of 1 hour or longer. Two auxiliary negative feedback loops, from ERK to MEK and RAF, placed downstream of the positive feedback, shape the temporal ERK activity profile but are dispensable for oscillations. Thus, the positive feedback introduces a hierarchy among negative feedback loops, such that the effect of a negative feedback depends on its position with respect to the positive feedback loop. Furthermore, a combination of the fast positive feedback involving slow-diffusing membrane components with slower negative feedbacks involving faster diffusing cytoplasmic components leads to local excitation/global inhibition dynamics, which allows the MAPK cascade to transmit paracrine EGF signals into spatially non-uniform ERK activity pulses.

Pre-frontal control of closed-loop limbic neurostimulation by rodents using a brain-computer interface

NASA Astrophysics Data System (ADS)

Widge, Alik S.; Moritz, Chet T.

2014-04-01

Objective. There is great interest in closed-loop neurostimulators that sense and respond to a patient's brain state. Such systems may have value for neurological and psychiatric illnesses where symptoms have high intraday variability. Animal models of closed-loop stimulators would aid preclinical testing. We therefore sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI). Approach. We trained rats to use an auditory BCI controlled by single units in prefrontal cortex (PFC). The BCI controlled electrical stimulation in the medial forebrain bundle, a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator. Main results. All animals successfully learned to use the BCI and neurostimulator, with closed-loop control of this challenging task demonstrated at 80% of PFC recording locations. Analysis across sessions and animals confirmed statistically robust BCI control and specific, rapid modulation of PFC activity. Significance. Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in PFC can be used to control a BCI without pre-training on a predicate task. This offers the potential for BCI-based treatments in refractory neurological and mental illness.

Diagnostics of solar flare plasma on the basis of microwave emission

NASA Astrophysics Data System (ADS)

Granat, A. D.; Stepanov, A. V.; Tsvetkov, L. I.

The diagnostic possibilities of the new four-wavelength (1.95-, 2.25-, 2.8-, and 3.5-cm) polarimeter of the 22-m radio telescope of the Crimean Astrophysical Observatory is illustrated by two events, on November 2 and 12, 1988. The characteristics of the oscillation structure on November 2, 1988 are used to estimate the plasma density (about 7 x 10 exp -11/cu cm) and temperature (about 3 x 10 exp 7 K) of eruptive flare plasma as well as the mean magnetic field through the flare loop (about 400 Gs). The sequence of bursts of November 12, 1988 could have been caused by protuberance oscillations, which makes it possible to estimate the temperature of the active region (about 2.4 x 10 exp 6 K).

Dismantling of Loop-Type Channel Equipment of MR Reactor in NRC 'Kurchatov Institute' - 13040

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

Volkov, Victor; Danilovich, Alexey; Zverkov, Yuri

2013-07-01

In 2009 the project of decommissioning of MR and RTF reactors was developed and approved by the Expert Authority of the Russian Federation (Gosexpertiza). The main objective of the decommissioning works identified in this project: - complete dismantling of reactor equipment and systems; - decontamination of reactor premises and site in accordance with the established sanitary and hygienic standards. At the preparatory stage (2008-2010) of the project the following works were executed: loop-type channels' dismantling in the storage pool; experimental fuel assemblies' removal from spent fuel repositories in the central hall; spent fuel assembly removal from the liquid-metal-cooled loop-type channelmore » of the reactor core and its placement into the SNF repository; and reconstruction of engineering support systems to the extent necessary for reactor decommissioning. The project assumes three main phases of dismantling and decontamination: - dismantling of equipment/pipelines of cooling circuits and loop-type channels, and auxiliary reactor equipment (2011-2012); - dismantling of equipment in underground reactor premises and of both MR and RTF in-vessel devices (2013-2014); - decontamination of reactor premises; rehabilitation of the reactor site; final radiation survey of reactor premises, loop-type channels and site; and issuance of the regulatory authorities' de-registration statement (2015). In 2011 the decommissioning license for the two reactors was received and direct MR decommissioning activities started. MR primary pipelines and loop-type facilities situated in the underground reactor hall were dismantled. Works were also launched to dismantle the loop-type channels' equipment in underground reactor premises; reactor buildings were reconstructed to allow removal of dismantled equipment; and the MR/RTF decommissioning sequence was identified. In autumn 2011 - spring 2012 results of dismantling activities performed are: - equipment from underground rooms (No. 66, 66A, 66B, 72, 64, 63) - as well as from water and gas loop corridors - was dismantled, with the total radwaste weight of 53 tons and the total removed activity of 5,0 x 10{sup 10} Bq; - loop-type channel equipment from underground reactor hall premises was dismantled; - 93 loop-type channels were characterized, chopped and removed, with radwaste of 2.6 x 10{sup 13} Bq ({sup 60}Co) and 1.5 x 10{sup 13} Bq ({sup 137}Cs) total activity removed from the reactor pool, fragmented and packaged. Some of this waste was placed into the high-level waste (HLW) repository of the Center. Dismantling works were executed with application of remotely operated mechanisms, which promoted decrease of radiation impact on the personnel. The average individual dose for the personnel was 1.9 mSv/year in 2011, and the collective dose is estimated as 0.0605 man x Sv/year. (authors)« less

Understanding the Hysteresis Loop Conundrum in Pharmacokinetic / Pharmacodynamic Relationships

PubMed Central

Louizos, Christopher; Yáñez, Jaime A.; Forrest, Laird; Davies, Neal M.

2015-01-01

Hysteresis loops are phenomena that sometimes are encountered in the analysis of pharmacokinetic and pharmacodynamic relationships spanning from pre-clinical to clinical studies. When hysteresis occurs it provides insight into the complexity of drug action and disposition that can be encountered. Hysteresis loops suggest that the relationship between drug concentration and the effect being measured is not a simple direct relationship, but may have an inherent time delay and disequilibrium, which may be the result of metabolites, the consequence of changes in pharmacodynamics or the use of a non-specific assay or may involve an indirect relationship. Counter-clockwise hysteresis has been generally defined as the process in which effect can increase with time for a given drug concentration, while in the case of clockwise hysteresis the measured effect decreases with time for a given drug concentration. Hysteresis loops can occur as a consequence of a number of different pharmacokinetic and pharmacodynamic mechanisms including tolerance, distributional delay, feedback regulation, input and output rate changes, agonistic or antagonistic active metabolites, uptake into active site, slow receptor kinetics, delayed or modified activity, time-dependent protein binding and the use of racemic drugs among other factors. In this review, each of these various causes of hysteresis loops are discussed, with incorporation of relevant examples of drugs demonstrating these relationships for illustrative purposes. Furthermore, the effect that pharmaceutical formulation has on the occurrence and potential change in direction of the hysteresis loop, and the major pharmacokinetic / pharmacodynamic modeling approaches utilized to collapse and model hysteresis are detailed. PMID:24735761

Therapeutic mechanisms of high-frequency stimulation in Parkinson's disease and neural restoration via loop-based reinforcement.

PubMed

Santaniello, Sabato; McCarthy, Michelle M; Montgomery, Erwin B; Gale, John T; Kopell, Nancy; Sarma, Sridevi V

2015-02-10

High-frequency deep brain stimulation (HFS) is clinically recognized to treat parkinsonian movement disorders, but its mechanisms remain elusive. Current hypotheses suggest that the therapeutic merit of HFS stems from increasing the regularity of the firing patterns in the basal ganglia (BG). Although this is consistent with experiments in humans and animal models of Parkinsonism, it is unclear how the pattern regularization would originate from HFS. To address this question, we built a computational model of the cortico-BG-thalamo-cortical loop in normal and parkinsonian conditions. We simulated the effects of subthalamic deep brain stimulation both proximally to the stimulation site and distally through orthodromic and antidromic mechanisms for several stimulation frequencies (20-180 Hz) and, correspondingly, we studied the evolution of the firing patterns in the loop. The model closely reproduced experimental evidence for each structure in the loop and showed that neither the proximal effects nor the distal effects individually account for the observed pattern changes, whereas the combined impact of these effects increases with the stimulation frequency and becomes significant for HFS. Perturbations evoked proximally and distally propagate along the loop, rendezvous in the striatum, and, for HFS, positively overlap (reinforcement), thus causing larger poststimulus activation and more regular patterns in striatum. Reinforcement is maximal for the clinically relevant 130-Hz stimulation and restores a more normal activity in the nuclei downstream. These results suggest that reinforcement may be pivotal to achieve pattern regularization and restore the neural activity in the nuclei downstream and may stem from frequency-selective resonant properties of the loop.

Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement

PubMed Central

Santaniello, Sabato; McCarthy, Michelle M.; Montgomery, Erwin B.; Gale, John T.; Kopell, Nancy; Sarma, Sridevi V.

2015-01-01

High-frequency deep brain stimulation (HFS) is clinically recognized to treat parkinsonian movement disorders, but its mechanisms remain elusive. Current hypotheses suggest that the therapeutic merit of HFS stems from increasing the regularity of the firing patterns in the basal ganglia (BG). Although this is consistent with experiments in humans and animal models of Parkinsonism, it is unclear how the pattern regularization would originate from HFS. To address this question, we built a computational model of the cortico-BG-thalamo-cortical loop in normal and parkinsonian conditions. We simulated the effects of subthalamic deep brain stimulation both proximally to the stimulation site and distally through orthodromic and antidromic mechanisms for several stimulation frequencies (20–180 Hz) and, correspondingly, we studied the evolution of the firing patterns in the loop. The model closely reproduced experimental evidence for each structure in the loop and showed that neither the proximal effects nor the distal effects individually account for the observed pattern changes, whereas the combined impact of these effects increases with the stimulation frequency and becomes significant for HFS. Perturbations evoked proximally and distally propagate along the loop, rendezvous in the striatum, and, for HFS, positively overlap (reinforcement), thus causing larger poststimulus activation and more regular patterns in striatum. Reinforcement is maximal for the clinically relevant 130-Hz stimulation and restores a more normal activity in the nuclei downstream. These results suggest that reinforcement may be pivotal to achieve pattern regularization and restore the neural activity in the nuclei downstream and may stem from frequency-selective resonant properties of the loop. PMID:25624501

Closed loop statistical performance analysis of N-K knock controllers

NASA Astrophysics Data System (ADS)

Peyton Jones, James C.; Shayestehmanesh, Saeed; Frey, Jesse

2017-09-01

The closed loop performance of engine knock controllers cannot be rigorously assessed from single experiments or simulations because knock behaves as a random process and therefore the response belongs to a random distribution also. In this work a new method is proposed for computing the distributions and expected values of the closed loop response, both in steady state and in response to disturbances. The method takes as its input the control law, and the knock propensity characteristic of the engine which is mapped from open loop steady state tests. The method is applicable to the 'n-k' class of knock controllers in which the control action is a function only of the number of cycles n since the last control move, and the number k of knock events that have occurred in this time. A Cumulative Summation (CumSum) based controller falls within this category, and the method is used to investigate the performance of the controller in a deeper and more rigorous way than has previously been possible. The results are validated using onerous Monte Carlo simulations, which confirm both the validity of the method and its high computational efficiency.

Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1

PubMed Central

Nguyen, Hai Dang; Yadav, Tribhuwan; Giri, Sumanprava; Saez, Borja; Graubert, Timothy A.; Zou, Lee

2017-01-01

R loop, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA), has emerged as a major source of genomic instability. RNaseH1, which cleaves the RNA in RNA:DNA hybrids, plays an important role in R loop suppression. Here, we show that replication protein A (RPA), a ssDNA-binding protein, interacts with RNaseH1 and colocalizes with both RNaseH1 and R loops in cells. In vitro, purified RPA directly enhances the association of RNaseH1 with RNA:DNA hybrids and stimulates the activity of RNaseH1 on R loops. An RPA binding-defective RNaseH1 mutant is not efficiently stimulated by RPA in vitro, fails to accumulate at R loops in cells, and loses the ability to suppress R loops and associated genomic instability. Thus, in addition to sensing DNA damage and replication stress, RPA is a sensor of R loops and a regulator of RNaseH1, extending the versatile role of RPA in suppression of genomic instability. PMID:28257700

KrasG12D-Induced IKK2/β/NF-κB Activation by IL-1α and p62 Feedforward Loops Is Required for Development of Pancreatic Ductal Adenocarcinoma

PubMed Central

Ling, Jianhua; Kang, Ya’an; Zhao, Ruiying; Xia, Qianghua; Lee, Dung-Fang; Chang, Zhe; Li, Jin; Peng, Bailu; Fleming, Jason B.; Wang, Huamin; Liu, Jinsong; Lemischka, Ihor R.; Hung, Mien-Chie; Chiao, Paul J.

2012-01-01

SUMMARY Constitutive Kras and NF-κB activation is identified as signature alterations in pancreatic ductal adenocarcinoma (PDAC). However, how NF-κB is activated in PDAC is not yet understood. Here, we report that pancreas-targeted IKK2/β inactivation inhibited NF-κB activation and PDAC development in KrasG12D and KrasG12D;Ink4a/ArfF/F mice, demonstrating a mechanistic link between IKK2/β and KrasG12D in PDAC inception. Our findings reveal that KrasG12D-activated AP-1 induces IL-1α, which, in turn, activates NF-κB and its target genes IL-1α and p62, to initiate IL-1α/p62 feedforward loops for inducing and sustaining NF-κB activity. Furthermore, IL-1α overexpression correlates with Kras mutation, NF-κB activity, and poor survival in PDAC patients. Therefore, our findings demonstrate the mechanism by which IKK2/β/NF-κB is activated by KrasG12D through dual feedforward loops of IL-1α/p62. PMID:22264792

Right- and left-loop short shRNAs have distinct and unusual mechanisms of gene silencing

PubMed Central

Dallas, Anne; Ilves, Heini; Ge, Qing; Kumar, Pavan; Shorenstein, Joshua; Kazakov, Sergei A.; Cuellar, Trinna L.; McManus, Michael T.; Behlke, Mark A.; Johnston, Brian H.

2012-01-01

Small hairpin RNAs (shRNAs) having duplex lengths of 25–29 bp are normally processed by Dicer into short interfering RNAs (siRNAs) before incorporation into the RNA-induced silencing complex (RISC). However, shRNAs of ≤19 bp [short shRNAs (sshRNAs)] are too short for Dicer to excise their loops, raising questions about their mechanism of action. sshRNAs are designated as L-type or R-type according to whether the loop is positioned 3′ or 5′ to the guide sequence, respectively. Using nucleotide modifications that inhibit RNA cleavage, we show that R- but not L-sshRNAs require loop cleavage for optimum activity. Passenger-arm slicing was found to be important for optimal functioning of L-sshRNAs but much less important for R-sshRNAs that have a cleavable loop. R-sshRNAs could be immunoprecipitated by antibodies to Argonaute-1 (Ago1); complexes with Ago1 contained both intact and loop-cleaved sshRNAs. In contrast, L-sshRNAs were immunoprecipitated with either Ago1 or Ago2 and were predominantly sliced in the passenger arm of the hairpin. However, ‘pre-sliced’ L-sshRNAs were inactive. We conclude that active L-sshRNAs depend on slicing of the passenger arm to facilitate opening of the duplex, whereas R-sshRNAs primarily act via loop cleavage to generate a 5′-phosphate at the 5′-end of the guide strand. PMID:22810205

Identification of Human Papillomavirus Type 16 L1 Surface Loops Required for Neutralization by Human Sera†

PubMed Central

Carter, Joseph J.; Wipf, Greg C.; Madeleine, Margaret M.; Schwartz, Stephen M.; Koutsky, Laura A.; Galloway, Denise A.

2006-01-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface. PMID:16641259

Identification of human papillomavirus type 16 L1 surface loops required for neutralization by human sera.

PubMed

Carter, Joseph J; Wipf, Greg C; Madeleine, Margaret M; Schwartz, Stephen M; Koutsky, Laura A; Galloway, Denise A

2006-05-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface.

Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells.

PubMed

Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R

2012-03-27

Recent results have indicated that factor Xa (FXa) cleaves protease-activated receptor 2 (PAR-2) to elicit protective intracellular signaling responses in endothelial cells. In this study, we investigated the molecular determinants of the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2 by FXa in endothelial cells transiently transfected with a PAR-2 cleavage reporter construct in which the extracellular domain of the receptor was fused to cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of PAR-2 by a series of FXa mutants containing mutations in different surface loops indicated that the acidic residues of 39-loop (Glu-36, Glu-37, and Glu-39) and the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150, and Arg-154), and 162-helix (Arg-165 and Lys-169) contribute to the specificity of receptor recognition by FXa on endothelial cells. This was evidenced by significantly reduced activity of mutants toward PAR-2 expressed on transfected cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants correlated with the extent of loss in their PAR-2-dependent intracellular signaling activity. Further characterization of FXa mutants indicated that, with the exception of basic residues of 162-helix, which play a role in the recognition specificity of the prothrombinase complex, none of the surface loop residues under study makes a significant contribution to the activity of FXa in the prothrombinase complex. These results provide new insight into mechanisms through which FXa specifically interacts with its macromolecular substrates in the clotting and signaling pathways.

Investigation of Inner Loop Flight Control Strategies for High-Speed Research

NASA Technical Reports Server (NTRS)

Newman, Brett; Kassem, Ayman

1999-01-01

This report describes the activities and findings conducted under contract NAS1-19858 with NASA Langley Research Center. Subject matter is the investigation of suitable flight control design methodologies and solutions for large, flexible high-speed vehicles. Specifically, methodologies are to address the inner control loops used for stabilization and augmentation of a highly coupled airframe system possibly involving rigid-body motion, structural vibrations, unsteady aerodynamics, and actuator dynamics. Techniques considered in this body of work are primarily conventional-based, and the vehicle of interest is the High-Speed Civil Transport (HSCT). Major findings include 1) current aeroelastic vehicle modeling procedures require further emphasis and refinement, 2) traditional and nontraditional inner loop flight control strategies employing a single feedback loop do not appear sufficient for highly flexible HSCT class vehicles, 3) inner loop flight control systems will, in all likelihood, require multiple interacting feedback loops, and 4) Ref. H HSCT configuration presents major challenges to designing acceptable closed-loop flight dynamics.