33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

Code of Federal Regulations, 2013 CFR

2013-07-01

... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

Code of Federal Regulations, 2011 CFR

2011-07-01

... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

Code of Federal Regulations, 2012 CFR

2012-07-01

... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

Improving primary care for persons with spinal cord injury: Development of a toolkit to guide care.

PubMed

Milligan, James; Lee, Joseph; Hillier, Loretta M; Slonim, Karen; Craven, Catharine

2018-05-07

To identify a set of essential components for primary care for patients with spinal cord injury (SCI) for inclusion in a point-of-practice toolkit for primary care practitioners (PCP) and identification of the essential elements of SCI care that are required in primary care and those that should be the focus of specialist care. Modified Delphi consensus process; survey methodology. Primary care. Three family physicians, six specialist physicians, and five inter-disciplinary health professionals completed surveys. Importance of care elements for inclusion in the toolkit (9-point scale: 1 = lowest level of importance, 9 = greatest level of importance) and identification of most responsible physician (family physician, specialist) for completing key categories of care. Open-ended comments were solicited. There was consensus between the respondent groups on the level of importance of various care elements. Mean importance scores were highest for autonomic dysreflexia, pain, and skin care and lowest for preventive care, social issues, and vital signs. Although, there was agreement across all respondents that family physicians should assume responsibility for assessing mental health, there was variability in who should be responsible for other care categories. Comments were related to the need for shared care approaches and capacity building and lack of knowledge and specialized equipment as barriers to optimal care. This study identified important components of SCI care to be included in a point-of-practice toolkit to facilitate primary care for persons with SCI.

Case Studies of Rock Reinforcement Components and Systems Testing

NASA Astrophysics Data System (ADS)

Thompson, A. G.; Villaescusa, E.

2014-09-01

Rock reinforcement is widely used in tunnels and surface and underground mines. A large number of proprietary products are available in various configurations of components. While the mechanical properties of the primary element are available from product brochures, the associated component properties may vary widely and adversely influence the overall performance of the system. Field pull out tests are most commonly used to measure the system response in the toe anchor region. However, the response of the collar region is less commonly considered but may be more important. Several case studies are described in which various components and systems of rock bolts and cable bolts have been subjected to static loading in the laboratory and in the field. The results generally demonstrate the importance of considering the properties of all the components and not simply those of the primary element. In some cases, the internal fixtures have strengths much less than the elements. Often it has also been found that the fixture at the collar has significantly less strength than the element and this will result in complete loss of function in restraining surface support hardware, such as plates, mesh and reinforced shotcrete.

Conditioned Reinforcement Value and Resistance to Change

ERIC Educational Resources Information Center

Shahan, Timothy A.; Podlesnik, Christopher A.

2008-01-01

Three experiments examined the effects of conditioned reinforcement value and primary reinforcement rate on resistance to change using a multiple schedule of observing-response procedures with pigeons. In the absence of observing responses in both components, unsignaled periods of variable-interval (VI) schedule food reinforcement alternated with…

Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

NASA Astrophysics Data System (ADS)

Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

2016-04-01

The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

TLR-2 IS INVOLVED IN AIRWAY EPITHELIAL CELL RESPONE TO AIR POLLUTION PARTICLES

EPA Science Inventory

Primary cultures of normal human airway epithelial cells (NHBE) respond to ambient air pollution particulate matter (PM) by increased production of the cytokine IL-8, and the induction of a number of oxidant stress response genes. Components of ambient air PM responsible for stim...

Ipsilateral medial olivocochlear reflex adaptation of the primary-source DPOAE component measured with pulsed tones

NASA Astrophysics Data System (ADS)

Dalhoff, Ernst; Zelle, Dennis; Gummer, Anthony W.

2015-12-01

Measurement of contralateral suppression or ipsilateral adaptation of DPOAE due to the medial olivocochlear reflex (MOCR) in humans has so far been complicated by interference between the two major contributors to a DPOAE signal, namely, the nonlinear and the reflection-source components. For instance, while the MOCR has been shown to act inhibitory to the cochlear amplifier, a considerable share of the measured responses has been reported to be of the excitatory type (e.g. 22% for contralateral adaptation in [11]), and it has been shown that the magnitudes of ipsilateral adaptation as well as contralateral suppression depend on the precise frequency choice relative to the position of dips in the DPOAE fine structure [3, 8]. To separate MOCR effects on both source components, we developed a paradigm consisting of five short f2 pulses presented during a 0.35 s on-period of the f1 primary within blocks of 1.35 s length. The responses at f1 and f2 were cancelled using the primary-tone phase variation technique [13]. In 16 normal-hearing subjects, we measured MOCR-induced ipsilateral adaptation at three near-by frequencies in the DPOAE fine structure, corresponding roughly to characteristic interference states between the two major source components of a DPOAE, i.e. constructive, destructive and quadrature interference. Measurements were performed in the frequency range 1.7 ≤ f2 ≤ 2 kHz, f2/f1 = 1.2, and with moderate primary-tone levels (L2 = 45 dB SPL, L1 = 57 dB SPL). Analysis of the DPOAE time traces showed that the nonlinear component typically presents inhibitory adaptation between the 1st and the 5th pulses (median: 0.92 dB). Fitting a single exponential function to the pooled data yielded adaptation of 1.49 dB. From 26 statistically significant MOCR effects (P < 0.1) ranging between 0.29 and 2.81 dB, no excitatory response was detected. The separation of the DPOAE sources when analysing MOCR effects on ipsilateral DPOAE offers the potential of investigating the human efferent system more specifically than hitherto possible.

Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

PubMed Central

Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

2011-01-01

Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

Ryan Beach | NREL

Science.gov Websites

team. His primary responsibilities include mechanical component design, test instrumentation and layout design, and data analysis for static and fatigue tests on full-scale wind turbine blades. Education B.S

Dissociating Stimulus-Set and Response-Set in the Context of Task-Set Switching

ERIC Educational Resources Information Center

Kieffaber, Paul D.; Kruschke, John K.; Cho, Raymond Y.; Walker, Philip M.; Hetrick, William P.

2013-01-01

The primary aim of the present research was to determine how "stimulus-set" and "response-set" components of task-set contribute to switch costs and conflict processing. Three experiments are described wherein participants completed an explicitly cued task-switching procedure. Experiment 1 established that task switches requiring a reconfiguration…

The effects of temperature on nest predation by mammals, birds, and snakes

Treesearch

W. Andrew Cox; F.R. Thompson III; J.L. Reidy

2013-01-01

Understanding how weather influences survival and reproduction is an important component of forecasting how climate change will influence wildlife population viability. Nest predation is the primary source of reproductive failure for passerine birds and can change in response to temperature. However, it is unclear which predator species are responsible for such...

The Role of Grain Size on Neutron Irradiation Response of Nanocrystalline Copper

PubMed Central

Mohamed, Walid; Miller, Brandon; Porter, Douglas; Murty, Korukonda

2016-01-01

The role of grain size on the developed microstructure and mechanical properties of neutron irradiated nanocrystalline copper was investigated by comparing the radiation response of material to the conventional micrograined counterpart. Nanocrystalline (nc) and micrograined (MG) copper samples were subjected to a range of neutron exposure levels from 0.0034 to 2 dpa. At all damage levels, the response of MG-copper was governed by radiation hardening manifested by an increase in strength with accompanying ductility loss. Conversely, the response of nc-copper to neutron irradiation exhibited a dependence on the damage level. At low damage levels, grain growth was the primary response, with radiation hardening and embrittlement becoming the dominant responses with increasing damage levels. Annealing experiments revealed that grain growth in nc-copper is composed of both thermally-activated and irradiation-induced components. Tensile tests revealed minimal change in the source hardening component of the yield stress in MG-copper, while the source hardening component was found to decrease with increasing radiation exposure in nc-copper. PMID:28773270

A probabilistic seismic risk assessment procedure for nuclear power plants: (II) Application

USGS Publications Warehouse

Huang, Y.-N.; Whittaker, A.S.; Luco, N.

2011-01-01

This paper presents the procedures and results of intensity- and time-based seismic risk assessments of a sample nuclear power plant (NPP) to demonstrate the risk-assessment methodology proposed in its companion paper. The intensity-based assessments include three sets of sensitivity studies to identify the impact of the following factors on the seismic vulnerability of the sample NPP, namely: (1) the description of fragility curves for primary and secondary components of NPPs, (2) the number of simulations of NPP response required for risk assessment, and (3) the correlation in responses between NPP components. The time-based assessment is performed as a series of intensity-based assessments. The studies illustrate the utility of the response-based fragility curves and the inclusion of the correlation in the responses of NPP components directly in the risk computation. ?? 2011 Published by Elsevier B.V.

Chemical, Biological, Radiological, and Nuclear Response Enterprise: A Way Ahead

DTIC Science & Technology

2012-03-12

Defense Support to Civilian Authorities (DSCA). After years of struggle and dozens of ill-fated attempts in response to a federally declared disaster of...support of civil authorities during major disasters as one of the primary Active Component Federal DOD response options. Lastly, it will consider...struggle and dozens of ill-fated attempts in response to a federally declared disaster of significant magnitude, the DOD has now developed a layered

The slow component of O(2) uptake is not accompanied by changes in muscle EMG during repeated bouts of heavy exercise in humans.

PubMed

Scheuermann, B W; Hoelting, B D; Noble, M L; Barstow, T J

2001-02-15

1. We hypothesized that either the recruitment of additional muscle motor units and/or the progressive recruitment of less efficient fast-twitch muscle fibres was the predominant contributor to the additional oxygen uptake (VO2) observed during heavy exercise. Using surface electromyographic (EMG) techniques, we compared the VO2 response with the integrated EMG (iEMG) and mean power frequency (MPF) response of the vastus lateralis with the VO2 response during repeated bouts of moderate (below the lactate threshold, < LT) and heavy (above the lactate threshold, > LT) intensity cycle ergometer exercise. 2. Seven male subjects (age 29 +/- 7 years, mean +/- S.D.) performed three transitions to a work rate (WR) corresponding to 90 % LT and two transitions to a work rate that would elicit a VO2 corresponding to 50 % of the difference between peak VO2 and the LT (i.e. Delta50 %, > LT1 and > LT2). 3. The VO2 slow component was significantly reduced by prior heavy intensity exercise (> LT1, 410 +/- 196 ml min(-1); > LT2, 230 +/- 191 ml min-1). The time constant (tau), amplitude (A) and gain (DeltaVO2/DeltaWR) of the primary VO2 response (phase II) were not affected by prior heavy exercise when a three-component, exponential model was used to describe the V2 response. 4. Integrated EMG and MPF remained relatively constant and at the same level throughout both > LT1 and > LT2 exercise and therefore were not associated with the VO2 slow component. 5. These data are consistent with the view that the increased O2 cost (i.e. VO2 slow component) associated with performing heavy exercise is coupled with a progressive increase in ATP requirements of the already recruited motor units rather than to changes in the recruitment pattern of slow versus fast-twitch motor units. Further, the lack of speeding of the kinetics of the primary VO2 component with prior heavy exercise, thought to represent the initial muscle VO2 response, are inconsistent with O2 delivery being the limiting factor in V > O2 kinetics during heavy exercise.

HIGH-RESOLUTION SPECTROSCOPY DURING ECLIPSE OF THE YOUNG SUBSTELLAR ECLIPSING BINARY 2MASS 0535-0546. II. SECONDARY SPECTRUM: NO EVIDENCE THAT SPOTS CAUSE THE TEMPERATURE REVERSAL

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

Mohanty, Subhanjoy; Stassun, Keivan G., E-mail: s.mohanty@imperial.ac.uk, E-mail: keivan.stassun@vanderbilt.edu

2012-10-10

We present high-resolution optical spectra of the young brown dwarf eclipsing binary 2M0535-05, obtained during eclipse of the higher-mass (primary) brown dwarf. Combined with our previous spectrum of the primary alone (Paper I), the new observations yield the spectrum of the secondary alone. We investigate, through a differential analysis of the two binary components, whether cool surface spots are responsible for suppressing the temperature of the primary. In Paper I, we found a significant discrepancy between the empirical surface gravity of the primary and that inferred via fine analysis of its spectrum. Here we find precisely the same discrepancy inmore » surface gravity, both qualitatively and quantitatively. While this may again be ascribed to either cool spots or model opacity errors, it implies that cool spots cannot be responsible for preferentially lowering the temperature of the primary: if they were, spot effects on the primary spectrum should be preferentially larger, and they are not. The T{sub eff}'s we infer for the primary and secondary, from the TiO-{epsilon} bands alone, show the same reversal, in the same ratio, as is empirically observed, bolstering the validity of our analysis. In turn, this implies that if suppression of convection by magnetic fields on the primary is the fundamental cause of the T{sub eff} reversal, then it cannot be a local suppression yielding spots mainly on the primary (though both components may be equally spotted), but a global suppression in the interior of the primary. We briefly discuss current theories of how this might work.« less

Modeling silicon diode energy response factors for use in therapeutic photon beams.

PubMed

Eklund, Karin; Ahnesjö, Anders

2009-10-21

Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer-Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 x 5 cm(2), 10 x 10 cm(2) and 20 x 20 cm(2) fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

The musculature and pupillary response of the great horned owl iris.

PubMed

Oliphant, L W; Johnson, M R; Murphy, C; Howland, H

1983-12-01

There is considerable confusion in the literature regarding the nature of the musculature of the avian iris. The most commonly held view is that both the sphincter and dilator are striated. The iris of the Great Horned Owl (Bubo virginianus) has a complex iridial musculature consisting of three circumferential components (a myoepithelium, smooth muscle and striated muscle) and two radial components (a well-developed myoepithelium and a few striated fibers). On the basis of the anatomy and relative development of these components, and a quantitative analysis of the pupillary reflex, it is proposed that the circumferential striated muscle is the primary pupillary constrictor and radial myoepithelium is the primary dilator. The annular band of smooth muscle may play an important role in maintaining pupillary size.

Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

PubMed

Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

2012-01-01

Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

Compression Strength of Composite Primary Structural Components

NASA Technical Reports Server (NTRS)

Johnson, Eric R.

1998-01-01

Research conducted under NASA Grant NAG-1-537 focussed on the response and failure of advanced composite material structures for application to aircraft. Both experimental and analytical methods were utilized to study the fundamental mechanics of the response and failure of selected structural components subjected to quasi-static loads. Most of the structural components studied were thin-walled elements subject to compression, such that they exhibited buckling and postbuckling responses prior to catastrophic failure. Consequently, the analyses were geometrically nonlinear. Structural components studied were dropped-ply laminated plates, stiffener crippling, pressure pillowing of orthogonally stiffened cylindrical shells, axisymmetric response of pressure domes, and the static crush of semi-circular frames. Failure of these components motivated analytical studies on an interlaminar stress postprocessor for plate and shell finite element computer codes, and global/local modeling strategies in finite element modeling. These activities are summarized in the following section. References to literature published under the grant are listed on pages 5 to 10 by a letter followed by a number under the categories of journal publications, conference publications, presentations, and reports. These references are indicated in the text by their letter and number as a superscript.

A Qualitative Study of Systemic Factors Contributing to Successful Implementation of Response to Intervention Programs in Elementary Schools

ERIC Educational Resources Information Center

White, Sheila B.

2017-01-01

Response to intervention (RTI), an educational reform effort designed to meet the needs of struggling learners, has been adopted by an increasing number of states as a primary component of their educational service delivery model for low-achieving students (Burns et al., 2013; Castillo & Batsche, 2012). RTI models are multi-tiered…

Characterization of Femoral Component Initial Stability and Cortical Strain in a Reduced Stem-Length Design.

PubMed

Small, Scott R; Hensley, Sarah E; Cook, Paige L; Stevens, Rebecca A; Rogge, Renee D; Meding, John B; Berend, Michael E

2017-02-01

Short-stemmed femoral components facilitate reduced exposure surgical techniques while preserving native bone. A clinically successful stem should ideally reduce risk for stress shielding while maintaining adequate primary stability for biological fixation. We asked (1) how stem-length changes cortical strain distribution in the proximal femur in a fit-and-fill geometry and (2) if short-stemmed components exhibit primary stability on par with clinically successful designs. Cortical strain was assessed via digital image correlation in composite femurs implanted with long, medium, and short metaphyseal fit-and-fill stem designs in a single-leg stance loading model. Strain was compared to a loaded, unimplanted femur. Bone-implant micromotion was then compared with reduced lateral shoulder short stem and short tapered-wedge designs in cyclic axial and torsional testing. Femurs implanted with short-stemmed components exhibited cortical strain response most closely matching that of the intact femur model, theoretically reducing the potential for proximal stress shielding. In micromotion testing, no difference in primary stability was observed as a function of reduced stem length within the same component design. Our findings demonstrate that within this fit-and-fill stem design, reduction in stem length improved proximal cortical strain distribution and maintained axial and torsional stability on par with other stem designs in a composite femur model. Short-stemmed implants may accommodate less invasive surgical techniques while facilitating more physiological femoral loading without sacrificing primary implant stability. Copyright © 2016 Elsevier Inc. All rights reserved.

The GP Patient Survey for use in primary care in the National Health Service in the UK--development and psychometric characteristics.

PubMed

Campbell, John; Smith, Patten; Nissen, Sonja; Bower, Peter; Elliott, Marc; Roland, Martin

2009-08-22

The UK National GP Patient Survey is one of the largest ever survey programmes of patients registered to receive primary health care, inviting five million respondents to report their experience of NHS primary healthcare. The third such annual survey (2008/9) involved the development of a new survey instrument. We describe the process of that development, and the findings of an extensive pilot survey in UK primary healthcare. The survey was developed following recognised guidelines and involved expert and stakeholder advice, cognitive testing of early versions of the survey instrument, and piloting of the questionnaire in a cross sectional pilot survey of 1,500 randomly selected individuals from the UK electoral register with two reminders to non-respondents. The questionnaire comprises 66 items addressing a range of aspects of UK primary healthcare. A response rate of 590/1500 (39.3%) was obtained. Non response to individual items ranged from 0.8% to 15.3% (median 5.2%). Participants did not always follow internal branching instructions in the questionnaire although electronic controls allow for correction of this problem in analysis. There was marked skew in the distribution of responses to a number of items indicating an overall favourable impression of care. Principal components analysis of 23 items offering evaluation of various aspects of primary care identified three components (relating to doctor or nurse care, or addressing access to care) accounting for 68.3% of the variance in the sample. The GP Patient Survey has been carefully developed and pilot-tested. Survey findings, aggregated at practice level, will be used to inform the distribution of pound sterling 65 million ($107 million) of UK NHS resource in 2008/9 and this offers the opportunity for NHS service planners and providers to take account of users' experiences of health care in planning and delivering primary healthcare in the UK.

Impaired Immune Response to Primary but Not to Booster Vaccination Against Hepatitis B in Older Adults.

PubMed

Weinberger, Birgit; Haks, Mariëlle C; de Paus, Roelof A; Ottenhoff, Tom H M; Bauer, Tanja; Grubeck-Loebenstein, Beatrix

2018-01-01

Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, most studies investigating vaccine-induced immune responses in the elderly do not analyze responses to neo-antigens but rather booster responses. However, age-related differences in the immune response could differentially affect primary versus recall responses. We therefore investigated the impact of age on primary and recall antibody responses following hepatitis B vaccination in young and older adults. Focused gene expression profiling was performed before and 1 day after the vaccination in order to identify gene signatures predicting antibody responses. Young (20-40 years; n  = 24) and elderly (>60 years; n  = 17) healthy volunteers received either a primary series (no prior vaccination) or a single booster shot (documented primary vaccination more than 10 years ago). Antibody titers were determined at days 0, 7, and 28, as well as 6 months after the vaccination. After primary vaccination, antibody responses were lower and delayed in the elderly compared to young adults. Non-responders after the three-dose primary series were only observed in the elderly group. Maximum antibody concentrations after booster vaccination were similar in both age groups. Focused gene expression profiling identified 29 transcripts that correlated with age at baseline and clustered in a network centered around type I interferons and pro-inflammatory cytokines. In addition, smaller 8- and 6-gene signatures were identified at baseline that associated with vaccine responsiveness during primary and booster vaccination, respectively. When evaluating the kinetic changes in gene expression profiles before and after primary vaccination, a 33-gene signature, dominated by IFN-signaling, pro-inflammatory cytokines, inflammasome components, and immune cell subset markers, was uncovered that was associated with vaccine responsiveness. By contrast, no such transcripts were identified during booster vaccination. Our results document that primary differs from booster vaccination in old age, in regard to antibody responses as well as at the level of gene signatures. www.clinicaltrialsregister.eu, this trial was registered at the EU Clinical Trial Register (EU-CTR) with the EUDRACT-Nr. 2013-002589-38.

Olfaction in the boll weevil,Anthonomus grandis Boh. (Coleoptera: Curculionidae): Electroantennogram studies.

PubMed

Dickens, J C

1984-12-01

Electroantennogram (EAG) techniques were utilized to measure the antennal olfactory responsiveness of adult boll weevils,Anthonomus grandis Boh. (Coleoptera: Curculionidae), to 38 odorants, including both insect and host plant (Gossypium hirsutum L.) volatiles. EAGs of both sexes were indicative of at least two receptor populations: one receptor population primarily responsive to pheromone components and related compounds, the other receptor population primarily responsive to plant odors. Similar responses to male aggregation pheromone components (i.e., compounds I, II, and III + IV) were obtained from both sexes, but females were slightly more sensitive to I. Both sexes were highly responsive to components of the "green leaf volatile complex," especially the six-carbon saturated and monounsaturated primary alcohols. Heptanal was the most active aldehyde tested. More acceptors responded to oxygenated monoterpenes than to monoterpene hydrocarbons. β-Bisabolol, the major volatile of cotton, was the most active sesquiterpene. In general, males, which are responsible for host selection and pheromone production, were more sensitive to plant odors than were females. In fact, males were as sensitive to β-bisabolol and heptanal as to aggregation pheromone components. Electrophysiological data are discussed with regard to the role of insect and host plant volatiles in host selection and aggregation behavior of the boll weevil.

Phenomenology and Signal Processing for UXO/Clutter Discrimination

DTIC Science & Technology

2009-08-01

29 Figure 25. (a) Pasion -Oldenburg model fit to the EMI response of a 4.2 inch mortar aligned transverse to the primary field...b) Comparison between the two-component and Pasion - Oldenburg model fits to the 4.2 inch mortar response...30 Figure 26. Pasion -Oldenburg exponent γ compared to the magnetic crossover time τM for model fits to EMI data collected

Genetic analysis of the gravitropic set-point angle in lateral roots of Arabidopsis

NASA Technical Reports Server (NTRS)

Mullen, J. L.; Hangarter, R. P.; Kiss, J. Z. (Principal Investigator)

2003-01-01

Research on gravity responses in plants has mostly focused on primary roots and shoots, which typically orient to a vertical orientation. However, the distribution of lateral organs and their characteristically non-vertical growth orientation are critical for the determination of plant form. For example, in Arabidopsis, when lateral roots emerge from the primary root, they grow at a nearly horizontal orientation. As they elongate, the roots slowly curve until they eventually reach a vertical orientation. The regulation of this lateral root orientation is an important component affecting overall root system architecture. We found that this change in orientation is not simply due to the onset of gravitropic competence, as non-vertical lateral roots are capable of both positive and negative gravitropism. Thus, the horizontal growth of new lateral roots appears to be determined by what is called the gravitropic set-point angle (GSA). This developmental control of the GSA of lateral roots in Arabidopsis provides a useful system for investigating the components involved in regulating gravitropic responses. Using this system, we have identified several Arabidopsis mutants that have altered lateral root orientations but maintain normal primary root orientation. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity

PubMed Central

Palm, Noah W.; Rosenstein, Rachel K.; Yu, Shuang; Schenten, Dominik; Florsheim, Esther; Medzhitov, Ruslan

2013-01-01

SUMMARY Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin. PMID:24210353

HPS4/SABRE regulates plant responses to phosphate starvation through antagonistic interaction with ethylene signalling

PubMed Central

Yu, Hailan; Luo, Nan; Sun, Lichao; Liu, Dong

2012-01-01

The phytohormone ethylene plays important roles in regulating plant responses to phosphate (Pi) starvation. To date, however, no molecular components have been identified that interact with ethylene signalling in regulating such responses. In this work, an Arabidopsis mutant, hps4, was characterized that exhibits enhanced responses to Pi starvation, including increased inhibition of primary root growth, enhanced expression of Pi starvation-induced genes, and overproduction of root-associated acid phosphatases. Molecular cloning indicated that hps4 is a new allele of SABRE, which was previously identified as an important regulator of cell expansion in Arabidopsis. HPS4/SABRE antagonistically interacts with ethylene signalling to regulate plant responses to Pi starvation. Furthermore, it is shown that Pi-starved hps4 mutants accumulate more auxin in their root tips than the wild type, which may explain the increased inhibition of their primary root growth when grown under Pi deficiency. PMID:22615140

Sequencing the Cortical Processing of Pitch-Evoking Stimuli using EEG Analysis and Source Estimation

PubMed Central

Butler, Blake E.; Trainor, Laurel J.

2012-01-01

Cues to pitch include spectral cues that arise from tonotopic organization and temporal cues that arise from firing patterns of auditory neurons. fMRI studies suggest a common pitch center is located just beyond primary auditory cortex along the lateral aspect of Heschl’s gyrus, but little work has examined the stages of processing for the integration of pitch cues. Using electroencephalography, we recorded cortical responses to high-pass filtered iterated rippled noise (IRN) and high-pass filtered complex harmonic stimuli, which differ in temporal and spectral content. The two stimulus types were matched for pitch saliency, and a mismatch negativity (MMN) response was elicited by infrequent pitch changes. The P1 and N1 components of event-related potentials (ERPs) are thought to arise from primary and secondary auditory areas, respectively, and to result from simple feature extraction. MMN is generated in secondary auditory cortex and is thought to act on feature-integrated auditory objects. We found that peak latencies of both P1 and N1 occur later in response to IRN stimuli than to complex harmonic stimuli, but found no latency differences between stimulus types for MMN. The location of each ERP component was estimated based on iterative fitting of regional sources in the auditory cortices. The sources of both the P1 and N1 components elicited by IRN stimuli were located dorsal to those elicited by complex harmonic stimuli, whereas no differences were observed for MMN sources across stimuli. Furthermore, the MMN component was located between the P1 and N1 components, consistent with fMRI studies indicating a common pitch region in lateral Heschl’s gyrus. These results suggest that while the spectral and temporal processing of different pitch-evoking stimuli involves different cortical areas during early processing, by the time the object-related MMN response is formed, these cues have been integrated into a common representation of pitch. PMID:22740836

Community governance in primary health care: towards an international Ideal Type.

PubMed

Meads, Geoffrey; Russell, Grant; Lees, Amanda

2017-10-01

Against a global background of increased resource management responsibilities for primary health care agencies, general medical practices, in particular, are increasingly being required to demonstrate the legitimacy of their decision making in market oriented environments. In this context a scoping review explores the potential utility for health managers in primary health care of community governance as a policy concept. The review of recent research suggests that applied learning from international health systems with enhanced approaches to public and patient involvement may contribute to meeting this requirement. Such approaches often characterise local health systems in Latin America and North West Europe where innovative models are beginning to respond effectively to the growing demands on general practice. The study design draws on documentary and secondary data analyses to identify common components of community governance from the countries in these regions, supplemented by other relevant international studies and sources where appropriate. Within a comprehensive framework of collaborative governance the components are aggregated in an Ideal Type format to provide a point of reference for possible adaptation and transferable learning across market oriented health systems. Each component is illustrated with international exemplars from recent organisational practices in primary health care. The application of community governance is considered for the particular contexts of GP led Clinical Commissioning Groups in England and Primary Health Networks in Australia. Some components of the Ideal Type possess potentially powerful negative as well as positive motivational effects, with PPI at practice levels sometimes hindering the development of effective local governance. This highlights the importance of careful and competent management of the growing resources attributed to primary health care agencies, which possess an increasingly diverse range of non-governmental status. Future policy and research priorities are outlined. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Modified ADALINE algorithm for harmonic estimation and selective harmonic elimination in inverters

NASA Astrophysics Data System (ADS)

Vasumathi, B.; Moorthi, S.

2011-11-01

In digital signal processing, algorithms are very well developed for the estimation of harmonic components. In power electronic applications, an objective like fast response of a system is of primary importance. An effective method for the estimation of instantaneous harmonic components, along with conventional harmonic elimination technique, is presented in this article. The primary function is to eliminate undesirable higher harmonic components from the selected signal (current or voltage) and it requires only the knowledge of the frequency of the component to be eliminated. A signal processing technique using modified ADALINE algorithm has been proposed for harmonic estimation. The proposed method stays effective as it converges to a minimum error and brings out a finer estimation. A conventional control based on pulse width modulation for selective harmonic elimination is used to eliminate harmonic components after its estimation. This method can be applied to a wide range of equipment. The validity of the proposed method to estimate and eliminate voltage harmonics is proved with a dc/ac inverter as a simulation example. Then, the results are compared with existing ADALINE algorithm for illustrating its effectiveness.

STRESSOR-RESPONSE RELATIONSHIPS: THE FOUNDATION FOR CHARACTERIZING EFFECTS

EPA Science Inventory

This research has 4 main components. The first focuses on developing the scientific information needed to extrapolate data from one or a few tested species to species of primary concern, e.g., the need to extrapolate data from domesticated birds to piscivorous avian species when...

Systematic mapping of two component response regulators to gene targets in a model sulfate reducing bacterium.

PubMed

Rajeev, Lara; Luning, Eric G; Dehal, Paramvir S; Price, Morgan N; Arkin, Adam P; Mukhopadhyay, Aindrila

2011-10-12

Two component regulatory systems are the primary form of signal transduction in bacteria. Although genomic binding sites have been determined for several eukaryotic and bacterial transcription factors, comprehensive identification of gene targets of two component response regulators remains challenging due to the lack of knowledge of the signals required for their activation. We focused our study on Desulfovibrio vulgaris Hildenborough, a sulfate reducing bacterium that encodes unusually diverse and largely uncharacterized two component signal transduction systems. We report the first systematic mapping of the genes regulated by all transcriptionally acting response regulators in a single bacterium. Our results enabled functional predictions for several response regulators and include key processes of carbon, nitrogen and energy metabolism, cell motility and biofilm formation, and responses to stresses such as nitrite, low potassium and phosphate starvation. Our study also led to the prediction of new genes and regulatory networks, which found corroboration in a compendium of transcriptome data available for D. vulgaris. For several regulators we predicted and experimentally verified the binding site motifs, most of which were discovered as part of this study. The gene targets identified for the response regulators allowed strong functional predictions to be made for the corresponding two component systems. By tracking the D. vulgaris regulators and their motifs outside the Desulfovibrio spp. we provide testable hypotheses regarding the functions of orthologous regulators in other organisms. The in vitro array based method optimized here is generally applicable for the study of such systems in all organisms.

Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways.

PubMed Central

Müller, M; Laxton, C; Briscoe, J; Schindler, C; Improta, T; Darnell, J E; Stark, G R; Kerr, I M

1993-01-01

Mutants in complementation group U3, completely defective in the response of all genes tested to interferons (IFNs) alpha and gamma, do not express the 91 and 84 kDa polypeptide components of interferon-stimulated gene factor 3 (ISGF3), a transcription factor known to play a primary role in the IFN-alpha response pathway. The 91 and 84 kDa polypeptides are products of a single gene. They result from differential splicing and differ only in a 38 amino acid extension at the C-terminus of the 91 kDa polypeptide. Complementation of U3 mutants with cDNA constructs expressing the 91 kDa product at levels comparable to those observed in induced wild-type cells completely restored the response to both IFN-alpha and -gamma and the ability to form ISGF3. Complementation with the 84 kDa component similarly restored the ability to form ISGF3 and, albeit to a lower level, the IFN-alpha response of all genes tested so far. It failed, however, to restore the IFN-gamma response of any gene analysed. The precise nature of the DNA motifs and combination of factors required for the transcriptional response of all genes inducible by IFN-alpha and -gamma remains to be established. The results presented here, however, emphasize the apparent general requirement of the 91 kDa polypeptide in the primary transcriptional response to both types of IFN. Images PMID:7693454

Recommendations for portable supplemental meteorological instrumentation for incident response

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

Brown, R.M.; Tichler, J.L.

The Nuclear Regulatory Commission (NRC) staff requested technical assistance in recommending portable supplementary meteorological instrumentation which can be deployed to nuclear power plant sites in response to incidents. A supplementary meteorological system (SMS), whose primary function is to collect, analyze and disseminate supplemental meteorological information, is recommended. Instrument specifications are discussed along with maintenance and staffing requirements. A cost evaluation of the components is made. 5 refs., 1 fig.

Effects of temporal primary-tone arrangement on DPOAE properties in humans

NASA Astrophysics Data System (ADS)

Zelle, Dennis; Krokenberger, Michael; Gummer, Anthony W.; Dalhoff, Ernst

2018-05-01

Distortion-product otoacoustic emissions (DPOAEs) emerge as a by-product of the nonlinear amplification of sound waves in the cochlea when presenting two tones of frequencies f1 and f2. According to a widely accepted model, DPOAEs comprise two main components, which can be separated in the time domain using short stimulus pulses. The present study utilized two acquisition paradigms with different primary-tone arrangements, denoted as SP-f1 and SP-f2, to investigate the nonlinear-distortion component arising near the f2-tonotopic site on the basilar membrane. In SP-f2, a conventional paradigm, the f1 tone was presented for 25 ms, whereas the f2 tone was switched on 5 ms after f1 onset for frequency-dependent durations between 3 and 11 ms to elicit the DPOAE. SP-f1 interchanged the temporal arrangement and durations of the primary tones. DPOAEs were recorded at eight frequencies (f2 = 1 - 8 kHz; f2/f1 = 1.2) and five primary-tone levels L2 = 30 - 70 dB SPL in 56 normal-hearing ears from 33 subjects. Comparison between the corresponding DPOAE responses revealed significantly larger amplitudes and shorter latencies of the nonlinear-distortion component for SP-f1, i.e. when the f1 short pulse triggers DPOAE generation.

HANFORD DOUBLE SHELL TANK THERMAL AND SEISMIC PROJECT SEISMIC ANALYSIS IN SUPPORT OF INCREASED LIQUID LEVEL IN 241-AP TANK FARMS

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

TC MACKEY; FG ABATT; MW RINKER

2009-01-14

The essential difference between Revision 1 and the original issue of this report is in the spring constants used to model the anchor bolt response for the anchor bolts that tie the steel dome of the primary tank to the concrete tank dome. Consequently, focus was placed on the changes in the anchor bolt responses, and a full reevaluation of all tank components was judged to be unnecessary. To confirm this judgement, primary tank stresses from the revised analysis of the BES-BEC case are compared to the original analysis and it was verified that the changes are small, as expected.

The Evolution of Two-Component Signal Transduction Systems

PubMed Central

Capra, Emily J.; Laub, Michael T.

2014-01-01

To exist in a wide range of environmental niches, bacteria must sense and respond to a myriad of external signals. A primary means by which this occurs is through two-component signal transduction pathways, typically comprised of a histidine kinase that receives the input stimuli and a response regulator that effects an appropriate change in cellular physiology. Histidine kinases and response regulators have an intrinsic modularity that separates signal input, phosphotransfer, and output response; this modularity has allowed bacteria to dramatically expand and diversify their signaling capabilities. Recent work has begun to reveal the molecular basis by which two-component proteins evolve. How and why do orthologous signaling proteins diverge? How do cells gain new pathways and recognize new signals? What changes are needed to insulate a new pathway from existing pathways? What constraints are there on gene duplication and lateral gene transfer? Here, we review progress made in answering these questions, highlighting how the integration of genome sequence data with experimental studies is providing major new insights. PMID:22746333

Making Morning Circle Meaningful

ERIC Educational Resources Information Center

Bruce, Susan; Fasy, Cara; Gulick, Jessica; Jones, Jill; Pike, Elizabeth

2006-01-01

Morning Circle, also known as Morning Meeting, is often a daily lesson in both general education and special education classrooms. The primary purpose of the Circle is to support each child to establish membership in the class while developing a classroom community and culture. The Responsive Classroom Approach recommends four Circle components:…

Higher fertilizer inputs increase fitness traits of brown planthopper in rice

USDA-ARS?s Scientific Manuscript database

ice (Oryza sativa L.) is the primary staple food source for more than half of the world's population. In many developing countries, increased use of fertilizers is a response to increase demand for rice. In this study, we investigated the effects of three principal fertilizer components (nitrogen, p...

Semiochemical-mediated flight responses of sap beetle vectors of oak wilt, Ceratocystis fagacearum

Treesearch

John F. Kyhl; Robert J. Bartelt; Allard Cosse; Jennifer Juzwik; Steven J. Seybold

2002-01-01

The sap beetle, Colopterus truncatus (Coleoptera: Nitidulidae), is one of the primary vectors of the oak wilt pathogen, Ceratocystis fagacearum, in the north-central United States. Field behavioral assays utilizing various release rates and blends of three methyl-branched hydrocarbon aggregation pheromone components showed that...

Visual-Vestibular Responses During Space Flight

NASA Technical Reports Server (NTRS)

Reschke, M. F.; Kozlovskaya, I. B.; Paloski, W. H.

1999-01-01

Given the documented disruptions that occur in spatial orientation during space flight and the putative sensory-motor information underlying eye and head spatial coding, the primary purpose of this paper is to examine components of the target acquisition system in subjects free to make head and eye movements in three dimensional space both during and following adaptation to long duration space flight. It is also our intention to suggest a simple model of adaptation that has components in common with cerebellar disorders whose neurobiological substrate has been identified.

Reticular influences on primary and augmenting responses in the somatosensory cortex.

PubMed

Steriade, M; Morin, D

1981-01-26

The effects of brief, conditioning trains of high-frequency pulses to the midbrain reticular formation (RF) on primary and augmenting responses of somatosensory (SI) cortex were investigated. Testing stimulation was applied to the ventrobasal (VB) thalamus or to the white matter (WM) beneath SI in VB-lesioned animals. The RF-elicited EEG activation was associated with increased firing rates of SI neurons, enhanced probability of early synaptic discharges to VB or WM stimuli, and significantly reduced duration of the suppressed firing period following an afferent VB or WM volley. The diminished latency of the postinhibitory rebound under RF stimulation had the consequence that, within 10/sec shock-train, the second stimulus was delivered following completion of the rebound component and, instead of an augmented potential, generated a field response of primary-type. The dependence of the RF-induced change in augmenting potentials upon the sharpening effect exerted on the preceding inhibitory-rebound sequence was corroborated by analyzing the RF influence on neurons with different time-course of recovery from inhibition. The replacement of augmenting potentials by primary responses under RF stimulation is advanced as the mechanism behind the obliteration of spontaneously developing 'type I' spindle-waves during EEG arousal. The demonstration of RF influences on SI responses to WM stimulation in VB-lesioned animals points out the cortical level of the effects. The reticulo-thalamo-cortical pathways underlying these influences are discussed.

Systematic mapping of two component response regulators to gene targets in a model sulfate reducing bacterium

PubMed Central

2011-01-01

Background Two component regulatory systems are the primary form of signal transduction in bacteria. Although genomic binding sites have been determined for several eukaryotic and bacterial transcription factors, comprehensive identification of gene targets of two component response regulators remains challenging due to the lack of knowledge of the signals required for their activation. We focused our study on Desulfovibrio vulgaris Hildenborough, a sulfate reducing bacterium that encodes unusually diverse and largely uncharacterized two component signal transduction systems. Results We report the first systematic mapping of the genes regulated by all transcriptionally acting response regulators in a single bacterium. Our results enabled functional predictions for several response regulators and include key processes of carbon, nitrogen and energy metabolism, cell motility and biofilm formation, and responses to stresses such as nitrite, low potassium and phosphate starvation. Our study also led to the prediction of new genes and regulatory networks, which found corroboration in a compendium of transcriptome data available for D. vulgaris. For several regulators we predicted and experimentally verified the binding site motifs, most of which were discovered as part of this study. Conclusions The gene targets identified for the response regulators allowed strong functional predictions to be made for the corresponding two component systems. By tracking the D. vulgaris regulators and their motifs outside the Desulfovibrio spp. we provide testable hypotheses regarding the functions of orthologous regulators in other organisms. The in vitro array based method optimized here is generally applicable for the study of such systems in all organisms. PMID:21992415

Toward precision smoking cessation treatment I: Moderator results from a factorial experiment.

PubMed

Piper, Megan E; Schlam, Tanya R; Cook, Jessica W; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin; Mermelstein, Robin; Collins, Linda M; Fiore, Michael C; Baker, Timothy B

2017-02-01

The development of tobacco use treatments that are effective for all smokers is critical to improving clinical and public health. The Multiphase Optimization Strategy (MOST) uses highly efficient factorial experiments to evaluate multiple intervention components for possible inclusion in an optimized tobacco use treatment. Factorial experiments permit analyses of the influence of patient characteristics on main and interaction effects of multiple, relatively discrete, intervention components. This study examined whether person-factor and smoking characteristics moderated the main or interactive effects of intervention components on 26-week self-reported abstinence rates. This fractional factorial experiment evaluated six smoking cessation intervention components among primary care patients (N=637): Prequit Nicotine Patch vs. None, Prequit Nicotine Gum vs. None, Preparation Counseling vs. None, Intensive Cessation In-Person Counseling vs. Minimal, Intensive Cessation Telephone Counseling vs. Minimal, and 16 vs. 8 Weeks of Combination Nicotine Replacement Therapy (NRT; nicotine patch+nicotine gum). Both psychiatric history and smoking heaviness moderated intervention component effects. In comparison with participants with no self-reported history of a psychiatric disorder, those with a positive history showed better response to 16- vs. 8-weeks of combination NRT, but a poorer response to counseling interventions. Also, in contrast to light smokers, heavier smokers showed a poorer response to counseling interventions. Heavy smokers and those with psychiatric histories demonstrated a differential response to intervention components. This research illustrates the use of factorial designs to examine the interactions between person characteristics and relatively discrete intervention components. Future research is needed to replicate these findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multiple components of surround modulation in primary visual cortex: multiple neural circuits with multiple functions?

PubMed Central

Nurminen, Lauri; Angelucci, Alessandra

2014-01-01

The responses of neurons in primary visual cortex (V1) to stimulation of their receptive field (RF) are modulated by stimuli in the RF surround. This modulation is suppressive when the stimuli in the RF and surround are of similar orientation, but less suppressive or facilitatory when they are cross-oriented. Similarly, in human vision surround stimuli selectively suppress the perceived contrast of a central stimulus. Although the properties of surround modulation have been thoroughly characterized in many species, cortical areas and sensory modalities, its role in perception remains unknown. Here we argue that surround modulation in V1 consists of multiple components having different spatio-temporal and tuning properties, generated by different neural circuits and serving different visual functions. One component arises from LGN afferents, is fast, untuned for orientation, and spatially restricted to the surround region nearest to the RF (the near-surround); its function is to normalize V1 cell responses to local contrast. Intra-V1 horizontal connections contribute a slower, narrowly orientation-tuned component to near-surround modulation, whose function is to increase the coding efficiency of natural images in manner that leads to the extraction of object boundaries. The third component is generated by topdown feedback connections to V1, is fast, broadly orientation-tuned, and extends into the far-surround; its function is to enhance the salience of behaviorally relevant visual features. Far- and near-surround modulation, thus, act as parallel mechanisms: the former quickly detects and guides saccades/attention to salient visual scene locations, the latter segments object boundaries in the scene. PMID:25204770

Optimizing the management of depression: primary care experience.

PubMed

Cameron, Catherine; Habert, Jeff; Anand, Leena; Furtado, Melissa

2014-12-01

This article is intended to identify some of the most important challenges faced by family physicians when treating MDD and to provide practical solutions. Key issues, reviewed from a primary care view point will include: treating to remission (and not just response), identification of high-risk groups, diagnosis, acute treatment approaches (including pharmacotherapy and the management of related side effects), the use of psychotherapy and somatic therapies, assessment of the adequacy of treatment including the assessment of remission, response measurement, optimal follow-up care throughout the phase of treatment, the key components of patient education and strategies for partial/limited response to the first-line antidepressant (switching, augmentation and combination strategies), how to provide support for improved treatment adherence, and approaches to prevent the recurrence of depressive episodes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Process evaluation of the data-driven quality improvement in primary care (DQIP) trial: active and less active ingredients of a multi-component complex intervention to reduce high-risk primary care prescribing.

PubMed

Grant, Aileen; Dreischulte, Tobias; Guthrie, Bruce

2017-01-07

Two to 4% of emergency hospital admissions are caused by preventable adverse drug events. The estimated costs of such avoidable admissions in England were £530 million in 2015. The data-driven quality improvement in primary care (DQIP) intervention was designed to prompt review of patients vulnerable from currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and anti-platelets and was found to be effective at reducing this prescribing. A process evaluation was conducted parallel to the trial, and this paper reports the analysis which aimed to explore response to the intervention delivered to clusters in relation to participants' perceptions about which intervention elements were active in changing their practice. Data generation was by in-depth interview with key staff exploring participant's perceptions of the intervention components. Analysis was iterative using the framework technique and drawing on normalisation process theory. All the primary components of the intervention were perceived as active, but at different stages of implementation: financial incentives primarily supported recruitment; education motivated the GPs to initiate implementation; the informatics tool facilitated sustained implementation. Participants perceived the primary components as interdependent. Intervention subcomponents also varied in whether and when they were active. For example, run charts providing feedback of change in prescribing over time were ignored in the informatics tool, but were motivating in some practices in the regular e-mailed newsletter. The high-risk NSAID and anti-platelet prescribing targeted was accepted as important by all interviewees, and this shared understanding was a key wider context underlying intervention effectiveness. This was a novel use of process evaluation data which examined whether and how the individual intervention components were effective from the perspective of the professionals delivering changed care to patients. These findings are important for reproducibility and roll-out of the intervention. ClinicalTrials.gov, NCT01425502 .

Time-Varying, Multi-Scale Adaptive System Reliability Analysis of Lifeline Infrastructure Networks

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

Gearhart, Jared Lee; Kurtz, Nolan Scot

2014-09-01

The majority of current societal and economic needs world-wide are met by the existing networked, civil infrastructure. Because the cost of managing such infrastructure is high and increases with time, risk-informed decision making is essential for those with management responsibilities for these systems. To address such concerns, a methodology that accounts for new information, deterioration, component models, component importance, group importance, network reliability, hierarchical structure organization, and efficiency concerns has been developed. This methodology analyzes the use of new information through the lens of adaptive Importance Sampling for structural reliability problems. Deterioration, multi-scale bridge models, and time-variant component importance aremore » investigated for a specific network. Furthermore, both bridge and pipeline networks are studied for group and component importance, as well as for hierarchical structures in the context of specific networks. Efficiency is the primary driver throughout this study. With this risk-informed approach, those responsible for management can address deteriorating infrastructure networks in an organized manner.« less

Plastid proteomics for elucidating iron limited remodeling of plastid physiology in diatoms

NASA Astrophysics Data System (ADS)

Gomes, K. M.; Nunn, B. L.; Jenkins, B. D.

2016-02-01

Diatoms are important primary producers in the world's oceans and their growth is constrained in large regions by low iron availability. This low iron-induced limitation of primary production is due to the requirement for iron in components of essential metabolic pathways including key chloroplast functions such as photosynthesis and nitrate assimilation. Diatoms can bloom and accumulate high biomass during introduction of iron into low iron waters, indicating adaptations allowing for their survival in iron-limited waters and rapid growth when iron becomes more abundant. Prior studies have shown that under iron limited stress, diatoms alter plastid-specific processes including components of electron transport, size of light harvesting capacity and chlorophyll content, suggesting plastid-specific protein regulation. Due to their complex evolutionary history, resulting from a secondary endosymbiosis, knowledge regarding the complement of plastid localized proteins remains limited in comparison to other model photosynthetic organisms. While in-silico prediction of diatom protein localization provides putative candidates for plastid-localization, these analyses can be limited as most plastid prediction models were developed using plants, primary endosymbionts. In order to characterize proteins enriched in diatom chloroplast and to understand how the plastid proteome is remodeled in response to iron limitation, we used mass spectrometry based proteomics to compare plastid- enriched protein fractions from Thalassiosira pseudonana, grown in iron replete and limited conditions. These analyses show that iron stress alters regulation of major metabolic pathways in the plastid including the Calvin cycle and fatty acid synthesis. These components provide promising targets to further characterize the plastid specific response to iron limitation.

Developmental assessment of the Fort St. Vrain version of the Composite HTGR Analysis Program (CHAP-2)

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

Stroh, K.R.

1980-01-01

The Composite HTGR Analysis Program (CHAP) consists of a model-independent systems analysis mainframe named LASAN and model-dependent linked code modules, each representing a component, subsystem, or phenomenon of an HTGR plant. The Fort St. Vrain (FSV) version (CHAP-2) includes 21 coded modules that model the neutron kinetics and thermal response of the core; the thermal-hydraulics of the reactor primary coolant system, secondary steam supply system, and balance-of-plant; the actions of the control system and plant protection system; the response of the reactor building; and the relative hazard resulting from fuel particle failure. FSV steady-state and transient plant data are beingmore » used to partially verify the component modeling and dynamic smulation techniques used to predict plant response to postulated accident sequences.« less

Token Economy: A Systematic Review of Procedural Descriptions.

PubMed

Ivy, Jonathan W; Meindl, James N; Overley, Eric; Robson, Kristen M

2017-09-01

The token economy is a well-established and widely used behavioral intervention. A token economy is comprised of six procedural components: the target response(s), a token that functions as a conditioned reinforcer, backup reinforcers, and three interconnected schedules of reinforcement. Despite decades of applied research, the extent to which the procedures of a token economy are described in complete and replicable detail has not been evaluated. Given the inherent complexity of a token economy, an analysis of the procedural descriptions may benefit future token economy research and practice. Articles published between 2000 and 2015 that included implementation of a token economy within an applied setting were identified and reviewed with a focus on evaluating the thoroughness of procedural descriptions. The results show that token economy components are regularly omitted or described in vague terms. Of the articles included in this analysis, only 19% (18 of 96 articles reviewed) included replicable and complete descriptions of all primary components. Missing or vague component descriptions could negatively affect future research or applied practice. Recommendations are provided to improve component descriptions.

Children's Mental Health as a Primary Care and Concern

PubMed Central

Tolan, Patrick H.; Dodge, Kenneth A.

2009-01-01

In response to the serious crisis in mental health care for children in the United States, this article proposes as a priority for psychology a comprehensive approach that treats mental health as a primary issue in child health and welfare. Consistent with the principles of a system of care and applying epidemiological, risk-development, and intervention-research findings, this approach emphasizes 4 components: easy access to effective professional clinical services for children exhibiting disorders; further development and application of sound prevention principles for high-risk youths; support for and access to short-term intervention in primary care settings; and greater recognition and promotion of mental health issues in common developmental settings and other influential systems. Integral to this approach is the need to implement these components simultaneously and to incorporate family-focused, culturally competent, evidence-based, and developmentally appropriate services. This comprehensive, simultaneous, and integrated approach is needed to achieve real progress in children's mental health in this country. PMID:16173893

Modeling aging effects on two-choice tasks: response signal and response time data.

PubMed

Ratcliff, Roger

2008-12-01

In the response signal paradigm, a test stimulus is presented, and then at one of a number of experimenter-determined times, a signal to respond is presented. Response signal, standard response time (RT), and accuracy data were collected from 19 college-age and 19 60- to 75-year-old participants in a numerosity discrimination task. The data were fit with 2 versions of the diffusion model. Response signal data were modeled by assuming a mixture of processes, those that have terminated before the signal and those that have not terminated; in the latter case, decisions are based on either partial information or guessing. The effects of aging on performance in the regular RT task were explained the same way in the models, with a 70- to 100-ms increase in the nondecision component of processing, more conservative decision criteria, and more variability across trials in drift and the nondecision component of processing, but little difference in drift rate (evidence). In the response signal task, the primary reason for a slower rise in the response signal functions for older participants was variability in the nondecision component of processing. Overall, the results were consistent with earlier fits of the diffusion model to the standard RT task for college-age participants and to the data from aging studies using this task in the standard RT procedure. Copyright (c) 2009 APA, all rights reserved.

Modeling Aging Effects on Two-Choice Tasks: Response Signal and Response Time Data

PubMed Central

Ratcliff, Roger

2009-01-01

In the response signal paradigm, a test stimulus is presented, and then at one of a number of experimenter-determined times, a signal to respond is presented. Response signal, standard response time (RT), and accuracy data were collected from 19 college-age and 19 60- to 75-year-old participants in a numerosity discrimination task. The data were fit with 2 versions of the diffusion model. Response signal data were modeled by assuming a mixture of processes, those that have terminated before the signal and those that have not terminated; in the latter case, decisions are based on either partial information or guessing. The effects of aging on performance in the regular RT task were explained the same way in the models, with a 70- to 100-ms increase in the nondecision component of processing, more conservative decision criteria, and more variability across trials in drift and the nondecision component of processing, but little difference in drift rate (evidence). In the response signal task, the primary reason for a slower rise in the response signal functions for older participants was variability in the nondecision component of processing. Overall, the results were consistent with earlier fits of the diffusion model to the standard RT task for college-age participants and to the data from aging studies using this task in the standard RT procedure. PMID:19140659

Spatio-Chromatic Adaptation via Higher-Order Canonical Correlation Analysis of Natural Images

PubMed Central

Gutmann, Michael U.; Laparra, Valero; Hyvärinen, Aapo; Malo, Jesús

2014-01-01

Independent component and canonical correlation analysis are two general-purpose statistical methods with wide applicability. In neuroscience, independent component analysis of chromatic natural images explains the spatio-chromatic structure of primary cortical receptive fields in terms of properties of the visual environment. Canonical correlation analysis explains similarly chromatic adaptation to different illuminations. But, as we show in this paper, neither of the two methods generalizes well to explain both spatio-chromatic processing and adaptation at the same time. We propose a statistical method which combines the desirable properties of independent component and canonical correlation analysis: It finds independent components in each data set which, across the two data sets, are related to each other via linear or higher-order correlations. The new method is as widely applicable as canonical correlation analysis, and also to more than two data sets. We call it higher-order canonical correlation analysis. When applied to chromatic natural images, we found that it provides a single (unified) statistical framework which accounts for both spatio-chromatic processing and adaptation. Filters with spatio-chromatic tuning properties as in the primary visual cortex emerged and corresponding-colors psychophysics was reproduced reasonably well. We used the new method to make a theory-driven testable prediction on how the neural response to colored patterns should change when the illumination changes. We predict shifts in the responses which are comparable to the shifts reported for chromatic contrast habituation. PMID:24533049

Spatio-chromatic adaptation via higher-order canonical correlation analysis of natural images.

PubMed

Gutmann, Michael U; Laparra, Valero; Hyvärinen, Aapo; Malo, Jesús

2014-01-01

Independent component and canonical correlation analysis are two general-purpose statistical methods with wide applicability. In neuroscience, independent component analysis of chromatic natural images explains the spatio-chromatic structure of primary cortical receptive fields in terms of properties of the visual environment. Canonical correlation analysis explains similarly chromatic adaptation to different illuminations. But, as we show in this paper, neither of the two methods generalizes well to explain both spatio-chromatic processing and adaptation at the same time. We propose a statistical method which combines the desirable properties of independent component and canonical correlation analysis: It finds independent components in each data set which, across the two data sets, are related to each other via linear or higher-order correlations. The new method is as widely applicable as canonical correlation analysis, and also to more than two data sets. We call it higher-order canonical correlation analysis. When applied to chromatic natural images, we found that it provides a single (unified) statistical framework which accounts for both spatio-chromatic processing and adaptation. Filters with spatio-chromatic tuning properties as in the primary visual cortex emerged and corresponding-colors psychophysics was reproduced reasonably well. We used the new method to make a theory-driven testable prediction on how the neural response to colored patterns should change when the illumination changes. We predict shifts in the responses which are comparable to the shifts reported for chromatic contrast habituation.

Overlapping and lineage-specific roles for the type-B response regulators of monocots and dicots.

PubMed

Kim, Hyo Jung; Kieber, Joseph J; Schaller, G Eric

2012-09-01

Cytokinins are plant hormones with profound roles in growth and development. Cytokinin signaling is mediated through a 'two-component' signaling system composed of histidine kinases, histidine-containing phosphotransfer proteins, and response regulators. Phylogenetic analysis of two-component signaling elements from the monocot rice and the dicot Arabidopsis reveals lineage-specific expansions of the type-B response regulators, transcription factors that act as positive regulators for the cytokinin signal. We recently reported in Plant Physiology on a functional analysis of rice type-B response regulators. A type-B response regulator from a subfamily comprised of both monocot and dicot type-B response regulators complemented an Arabidopsis type-B response regulator mutant, but a type-B response regulator from a monocot-specific subfamily generally did not. Here, we extend this analysis to demonstrate that the promoter of an Arabidopsis cytokinin primary response gene is induced by type-B response regulators from a shared subfamily, but not by one from a lineage-specific subfamily. These results support a model in which the type-B response regulators of monocots and dicots share conserved roles in the cytokinin signaling pathway but have also diverged to take on lineage-specific roles.

Manpower Planning for Wastewater Treatment Plants.

ERIC Educational Resources Information Center

Davies, J. Kenneth; And Others

This document discusses the components necessary in the development of a forecasting process by which manpower needs can be determined and the development of action programs by which the projected needs may be satisfied. The primary focus of this manual is directed at that person in a state agency who has the responsibility for planning the…

Protein kinase Cδ is a critical component of Dectin-1 signaling in primary human monocytes.

PubMed

Elsori, Deena H; Yakubenko, Valentin P; Roome, Talat; Thiagarajan, Praveena S; Bhattacharjee, Ashish; Yadav, Satya P; Cathcart, Martha K

2011-09-01

Zymosan, a mimic of fungal pathogens, and its opsonized form (ZOP) are potent stimulators of monocyte NADPH oxidase, resulting in the production of O(2)(.-), which is critical for host defense against fungal and bacterial pathogens and efficient immune responses; however, uncontrolled O(2)(.-) production may contribute to chronic inflammation and tissue injury. Our laboratory has focused on characterizing the signal transduction pathways that regulate NADPH oxidase activity in primary human monocytes. In this study, we examined the involvement of various pattern recognition receptors and found that Dectin-1 is the primary receptor for zymosan stimulation of O(2)(.-) via NADPH oxidase in human monocytes, whereas Dectin-1 and CR3 mediate the activation by ZOP. Further studies identified Syk and Src as important signaling components downstream of Dectin-1 and additionally identified PKCδ as a novel downstream signaling component for zymosan-induced O(2)(.-) as well as phagocytosis. Our results show that Syk and Src association with Dectin-1 is dependent on PKCδ activity and expression and demonstrate direct binding between Dectin-1 and PKCδ. Finally, our data show that PKCδ and Syk but not Src are required for Dectin-1-mediated phagocytosis. Taken together, our data identify Dectin-1 as the major PRR for zymosan in primary human monocytes and identify PKCδ as a novel downstream signaling kinase for Dectin-1-mediated regulation of monocyte NADPH oxidase and zymosan phagocytosis.

Effect of Range and Angular Velocity of Passive Movement on Somatosensory Evoked Magnetic Fields.

PubMed

Sugawara, Kazuhiro; Onishi, Hideaki; Yamashiro, Koya; Kojima, Sho; Miyaguchi, Shota; Kotan, Shinichi; Tsubaki, Atsuhiro; Kirimoto, Hikari; Tamaki, Hiroyuki; Shirozu, Hiroshi; Kameyama, Shigeki

2016-09-01

To clarify characteristics of each human somatosensory evoked field (SEF) component following passive movement (PM), PM1, PM2, and PM3, using high spatiotemporal resolution 306-channel magnetoencephalography and varying PM range and angular velocity. We recorded SEFs following PM under three conditions [normal range-normal velocity (NN), small range-normal velocity (SN), and small range-slow velocity (SS)] with changing movement range and angular velocity in 12 participants and calculated the amplitude, equivalent current dipole (ECD) location, and the ECD strength for each component. All components were observed in six participants, whereas only PM1 and PM3 in the other six. Clear response deflections at the ipsilateral hemisphere to PM side were observed in seven participants. PM1 amplitude was larger under NN and SN conditions, and mean ECD location for PM1 was at primary motor area. PM3 amplitude was larger under SN condition and mean ECD location for PM3 under SS condition was at primary somatosensory area. PM1 amplitude was dependent on the angular velocity of PM, suggesting that PM1 reflects afferent input from muscle spindle, whereas PM3 amplitude was dependent on the duration. The ECD for PM3 was located in the primary somatosensory cortex, suggesting that PM3 reflects cutaneous input. We confirmed the hypothesis for locally distinct generators and characteristics of each SEF component.

Component Control System for a Vehicle

NASA Technical Reports Server (NTRS)

Lee, Chunhao J. (Inventor); Fraser-Chanpong, Nathan (Inventor); Vitale, Robert L. (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Dawson, Andrew D. (Inventor); Guo, Raymond (Inventor); Waligora, Thomas M. (Inventor); Spain, Ivan (Inventor); Bluethmann, William J. (Inventor); Reed, Ryan M. (Inventor)

2016-01-01

A vehicle includes a chassis, a modular component, and a central operating system. The modular component is supported by the chassis. The central operating system includes a component control system, a primary master controller, and a secondary master controller. The component control system is configured for controlling the modular component. The primary and secondary master controllers are in operative communication with the component control system. The primary and secondary master controllers are configured to simultaneously transmit commands to the component control system. The component control system is configured to accept commands from the secondary master controller only when a fault occurs in the primary master controller.

Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression*

PubMed Central

Buggele, William A.; Johnson, Karen E.; Horvath, Curt M.

2012-01-01

The cellular response to virus infection is initiated by recognition of the invading pathogen and subsequent changes in gene expression mediated by both transcriptional and translational mechanisms. In addition to well established means of regulating antiviral gene expression, it has been demonstrated that RNA interference (RNAi) can play an important role in antiviral responses. Virus-derived small interfering RNA (siRNA) is a primary antiviral response exploited by plants and invertebrate animals, and host-encoded microRNA (miRNA) species have been clearly implicated in the regulation of innate and adaptive immune responses in mammals and other vertebrates. Examination of miRNA abundance in human lung cell lines revealed endogenous miRNAs, including miR-7, miR-132, miR-146a, miR-187, miR-200c, and miR-1275, to specifically accumulate in response to infection with two influenza A virus strains, A/Udorn/72 and A/WSN/33. Known antiviral response pathways, including Toll-like receptor, RIG-I-like receptor, and direct interferon or cytokine stimulation did not alter the abundance of the tested miRNAs to the extent of influenza A virus infection, which initiates primary miRNA transcription via a secondary response pathway. Gene expression profiling identified 26 cellular mRNAs targeted by these miRNAs, including IRAK1, MAPK3, and other components of innate immune signaling systems. PMID:22822053

Numerical study on static component generation from the primary Lamb waves propagating in a plate with nonlinearity

NASA Astrophysics Data System (ADS)

Wan, Xiang; Tse, Peter W.; Zhang, Xuhui; Xu, Guanghua; Zhang, Qing; Fan, Hongwei; Mao, Qinghua; Dong, Ming; Wang, Chuanwei; Ma, Hongwei

2018-04-01

Under the discipline of nonlinear ultrasonics, in addition to second harmonic generation, static component generation is another frequently used nonlinear ultrasonic behavior in non-destructive testing (NDT) and structural health monitoring (SHM) communities. However, most previous studies on static component generation are mainly based on using longitudinal waves. It is desirable to extend static component generation from primary longitudinal waves to primary Lamb waves. In this paper, static component generation from the primary Lamb waves is studied. Two major issues are numerically investigated. First, the mode of static displacement component generated from different primary Lamb wave modes is identified. Second, cumulative effect of static displacement component from different primary Lamb wave modes is also discussed. Our study results show that the static component wave packets generated from the primary S0, A0 and S1 modes share the almost same group velocity equal to the phase velocity of S0 mode tending to zero frequency c plate . The finding indicates that whether the primary mode is S0, A0 or S1, the static components generated from these primary modes always share the nature of S0 mode. This conclusion is also verified by the displacement filed of these static components that the horizontal displacement field is almost uniform and the vertical displacement filed is antisymmetric across the thickness of the plate. The uniform distribution of horizontal displacement filed enables the static component, regardless of the primary Lamb modes, to be a promising technique for evaluating microstructural damages buried in the interior of a structure. Our study also illustrates that the static components are cumulative regardless of whether the phase velocity of the primary and secondary waves is matched or not. This observation indicates that the static component overcomes the limitations of the traditional nonlinear Lamb waves satisfying phase velocity matching condition to achieve cumulative second harmonic generation. This nature also enables the primary Lamb waves excited at a low center frequency to generate static component used for inspecting large-scale structures with micro-scale damages.

Investigating the adaptive immune response in influenza and secondary bacterial pneumonia and nanoparticle based therapeutic delivery

NASA Astrophysics Data System (ADS)

Chakravarthy, Krishnan V.

In early 2000, influenza and its associated complications were the 7 th leading cause of death in the United States[1-4]. As of today, this major health problem has become even more of a concern, with the possibility of a potentially devastating avian flu (H5N1) or swine flu pandemic (H1N1). According to the Centers for Disease Control (CDC), over 10 countries have reported transmission of influenza A (H5N1) virus to humans as of June 2006 [5]. In response to this growing concern, the United States pledged over $334 million dollars in international aid for battling influenza[1-4]. The major flu pandemic of the early 1900's provided the first evidence that secondary bacterial pneumonia (not primary viral pneumonia) was the major cause of death in both community and hospital-based settings. Secondary bacterial infections currently account for 35-40% mortality following a primary influenza viral infection [1, 6]. The first component of this work addresses the immunological mechanisms that predispose patients to secondary bacterial infections following a primary influenza viral infection. By assessing host immune responses through various immune-modulatory tools, such as use of volatile anesthetics (i.e. halothane) and Apilimod/STA-5326 (an IL-12/Il-23 transcription blocker), we provide experimental evidence that demonstrates that the overactive adaptive Th1 immune response is critical in mediating increased susceptibility to secondary bacterial infections. We also present data that shows that suppressing the adaptive Th1 immune response enhances innate immunity, specifically in alveolar macrophages, by favoring a pro anti-bacterial phenotype. The second component of this work addresses the use of nanotechnology to deliver therapeutic modalities that affect the primary viral and associated secondary bacterial infections post influenza. First, we used surface functionalized quantum dots for selective targeting of lung alveolar macrophages both in vitro and in vivo. Second, we targeted human bronchial epithelial cells (A549) with gold nanoparticles complexed to 5'PPP-ssRNA to induce RIG-I cytoplasmic ligand, which results in induction of type 1 interferon and concomitant reduction in influenza viral replication. 1-6. Please see dissertation for all references.

Directing Improvements in Primary Care Patient Experience through Analysis of Service Quality.

PubMed

Hudson Smith, Mel; Smith, David

2018-06-03

To examine the influence of dimensions of service quality on patient experience of primary care. Data from the national GP Patient Survey in England 2014/15, with responses from 858,351 patients registered at 7,918 practices. Expert panel and principal component analysis helped identify relevant dimensions of service quality. Regression was then used to examine the relationships between these dimensions and reported patient experience. Aggregated scores for each practice were used, comprising the proportion of positive responses to each element of the study. Of eight service quality dimensions identified, six have statistically significant impacts on patient experience but only two have large effects. Patient experience is highly influenced by practice responsiveness and the interactions with the physician. Other dimensions have small or even slightly negative influence. Service quality provided by nurses has negligible effect on patient experience. To improve patient experience in primary health care, efforts should focus on practice responsiveness and interactions with the physician. Other areas have little influence over patient experience. This suggests a gap in patients' perspectives on health care, which has policy implications for patient education. © Health Research and Educational Trust.

Facile hyphenation of gas chromatography and a microcantilever array sensor for enhanced selectivity.

PubMed

Chapman, Peter J; Vogt, Frank; Dutta, Pampa; Datskos, Panos G; Devault, Gerald L; Sepaniak, Michael J

2007-01-01

The very simple coupling of a standard, packed-column gas chromatograph with a microcantilever array (MCA) is demonstrated for enhanced selectivity and potential analyte identification in the analysis of volatile organic compounds (VOCs). The cantilevers in MCAs are differentially coated on one side with responsive phases (RPs) and produce bending responses of the cantilevers due to analyte-induced surface stresses. Generally, individual components are difficult to elucidate when introduced to MCA systems as mixtures, although pattern recognition techniques are helpful in identifying single components, binary mixtures, or composite responses of distinct mixtures (e.g., fragrances). In the present work, simple test VOC mixtures composed of acetone, ethanol, and trichloroethylene (TCE) in pentane and methanol and acetonitrile in pentane are first separated using a standard gas chromatograph and then introduced into a MCA flow cell. Significant amounts of response diversity to the analytes in the mixtures are demonstrated across the RP-coated cantilevers of the array. Principal component analysis is used to demonstrate that only three components of a four-component VOC mixture could be identified without mixture separation. Calibration studies are performed, demonstrating a good linear response over 2 orders of magnitude for each component in the primary study mixture. Studies of operational parameters including column temperature, column flow rate, and array cell temperature are conducted. Reproducibility studies of VOC peak areas and peak heights are also carried out showing RSDs of less than 4 and 3%, respectively, for intra-assay studies. Of practical significance is the facile manner by which the hyphenation of a mature separation technique and the burgeoning sensing approach is accomplished, and the potential to use pattern recognition techniques with MCAs as a new type of detector for chromatography with analyte-identifying capabilities.

Gravity response mechanisms of lateral organs and the control of plant architecture in Arabidopsis

NASA Astrophysics Data System (ADS)

Mullen, J.; Hangarter, R.

Most research on gravity responses in plants has focused on primary roots and shoots, which typically grow in a vertical orientation. However, the patterns of lateral organ formation and their growth orientation, which typically are not vertical, govern plant architecture. For example, in Arabidopsis, when lateral roots emerge from the primary root, they grow at a nearly horizontal orientation. As they elongate, the roots slowly curve until they eventually reach a vertical orientation. The regulation of this lateral root orientation is an important component affecting the overall root system architecture. We have found that this change in orientation is not simply due to the onset of gravitropic competence, as non-vertical lateral roots are capable of both positive and negative gravitropism. Thus, the horizontal growth of the new lateral roots is determined by what is called the gravitropic set-point angle (GSA). In Arabidopsis shoots, rosette leaves and inflorescence branches also display GSA-dependent developmental changes in their orientation. The developmental control of the GSA of lateral organs in Arabidopsis provides us with a useful system for investigating the components involved in regulating directionality of tropistic responses. We have identified several Arabidopsis mutants that have either altered lateral root orientations, altered orientation of lateral organs in the shoot, or both, but maintain normal primary organ orientation. The mgsa ({m}odified {g}ravitropic {s}et-point {a}ngle) mutants with both altered lateral root and shoot orientation show that there are common components in the regulation of growth orientation in the different organs. Rosette leaves and lateral roots also have in common a regulation of positioning by red light. Further molecular and physiological analyses of the GSA mutants will provide insight into the basis of GSA regulation and, thus, a better understanding of how gravity controls plant architecture. [This work was supported by the National Aeronautics and Space Administration through grant no. NCC 2-1200.

Mitogen activated protein kinase 6 and MAP kinase phosphatase 1 are involved in the response of Arabidopsis roots to L-glutamate.

PubMed

López-Bucio, Jesús Salvador; Raya-González, Javier; Ravelo-Ortega, Gustavo; Ruiz-Herrera, León Francisco; Ramos-Vega, Maricela; León, Patricia; López-Bucio, José; Guevara-García, Ángel Arturo

2018-03-01

The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood. Through a combination of genetic analysis, in-gel kinase assays, detailed cell elongation and division measurements and confocal analysis of expression of auxin, quiescent center and stem cell niche related genes, the critical roles of L-Glu in primary root growth acting through the mitogen-activated protein kinase 6 (MPK6) and the dual specificity serine-threonine-tyrosine phosphatase MKP1 could be revealed. In-gel phosphorylation assays revealed a rapid and dose-dependent induction of MPK6 and MPK3 activities in wild-type Arabidopsis seedlings in response to L-Glu. Mutations in MPK6 or MKP1 reduced or increased root cell division and elongation in response to L-Glu, possibly modulating auxin transport and/or response, but in a PLETHORA1 and 2 independent manner. Our data highlight MPK6 and MKP1 as components of an L-Glu pathway linking the auxin response, and cell division for primary root growth.

Jet Stability and the Generation of Superluminal and Stationary Components

NASA Technical Reports Server (NTRS)

Agudo, Ivan; Gomez, Jose-Luis; Marti, Jose-Maria; Ibanez, Jose-Maria; Marscher, Alan P.; Alberdi, Antonio; Aloy, Miguel-Angel; Hardee, Philip E.

2001-01-01

We present a numerical simulation of the response of an expanding relativistic jet to the ejection of a superluminal component. The simulation has been performed with a relativistic time-dependent hydrodynamical code from which simulated radio maps are computed by integrating the transfer equations for synchrotron radiation. The interaction of the superluminal component with the underlying jet results in the formation of multiple conical shocks behind the main perturbation. These trailing components can be easily distinguished because they appear to be released from the primary superluminal component instead of being ejected from the core. Their oblique nature should also result in distinct polarization properties. Those appearing closer to the core show small apparent motions and a very slow secular decrease in brightness and could be identified as stationary components. Those appearing farther downstream are weaker and can reach superluminal apparent motions. The existence of these trailing components indicates that not all observed components necessarily represent major perturbations at the jet inlet; rather, multiple emission components can be generated by a single disturbance in the jet. While the superluminal component associated with the primary perturbation exhibits a rather stable pattern speed, trailing components have velocities that increase with distance from the core but move at less than the jet speed. The trailing components exhibit motion and structure consistent with the triggering of pinch modes by the superluminal component. The increase in velocity of the trailing components is an indirect consequence of the acceleration of the expanding fluid, which is assumed to be relativistically hot; if observed, such accelerations would therefore favor an electron-positron (as opposed to proton rest mass) dominated jet.

Framework for a U.S. Geological Survey Hydrologic Climate-Response Program in Maine

USGS Publications Warehouse

Hodgkins, Glenn A.; Lent, Robert M.; Dudley, Robert W.; Schalk, Charles W.

2009-01-01

This report presents a framework for a U.S. Geological Survey (USGS) hydrologic climate-response program designed to provide early warning of changes in the seasonal water cycle of Maine. Climate-related hydrologic changes on Maine's rivers and lakes in the winter and spring during the last century are well documented, and several river and lake variables have been shown to be sensitive to air-temperature changes. Monitoring of relevant hydrologic data would provide important baseline information against which future climate change can be measured. The framework of the hydrologic climate-response program presented here consists of four major parts: (1) identifying homogeneous climate-response regions; (2) identifying hydrologic components and key variables of those components that would be included in a hydrologic climate-response data network - as an example, streamflow has been identified as a primary component, with a key variable of streamflow being winter-spring streamflow timing; the data network would be created by maintaining existing USGS data-collection stations and establishing new ones to fill data gaps; (3) regularly updating historical trends of hydrologic data network variables; and (4) establishing basins for process-based studies. Components proposed for inclusion in the hydrologic climate-response data network have at least one key variable for which substantial historical data are available. The proposed components are streamflow, lake ice, river ice, snowpack, and groundwater. The proposed key variables of each component have extensive historical data at multiple sites and are expected to be responsive to climate change in the next few decades. These variables are also important for human water use and (or) ecosystem function. Maine would be divided into seven climate-response regions that follow major river-basin boundaries (basins subdivided to hydrologic units with 8-digit codes or larger) and have relatively homogeneous climates. Key hydrologic variables within each climate-response region would be analyzed regularly to maintain up-to-date analyses of year-to-year variability, decadal variability, and longer term trends. Finally, one basin in each climate-response region would be identified for process-based hydrologic and ecological studies.

A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America.

PubMed

López, Pío; Arguedas Mohs, Adriano; Abdelnour Vásquez, Arturo; Consuelo-Miranda, Maria; Feroldi, Emmanuel; Noriega, Fernando; Jordanov, Emilia; B Chir, Siham; Zambrano, Betzana

2017-11-01

Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America. Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports. Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine. These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

Spectral responses of gravel beaches to tidal signals

NASA Astrophysics Data System (ADS)

Geng, Xiaolong; Boufadel, Michel C.

2017-01-01

Tides have been recognized as a major driving forcing affecting coastal aquifer system, and deterministic modeling has been very effective in elucidating mechanisms caused by tides. However, such modeling does not lend itself to capture embedded information in the signal, and rather focuses on the primary processes. Here, using yearlong data sets measured at beaches in Alaska Prince William Sound, we performed spectral and correlation analyses to identify temporal behavior of pore-water pressure, temperature and salinity. We found that the response of the beach system was characterized by fluctuations of embedded diurnal, semidiurnal, terdiurnal and quarterdiurnal tidal components. Hydrodynamic dispersion of salinity and temperature, and the thermal conductivity greatly affected pore water signals. Spectral analyses revealed a faster dissipation of the semi-diurnal component with respect to the diurnal components. Correlation functions showed that salinity had a relatively short memory of the tidal signal when inland freshwater recharge was large. In contrast, the signature of the tidal signal on pore-water temperature persisted for longer times, up to a week. We also found that heterogeneity greatly affected beach response. The response varied from a simple linear mapping in the frequency domain to complete modulation and masking of the input frequencies.

Noise reduction in functional near-infrared spectroscopy signals by independent component analysis

NASA Astrophysics Data System (ADS)

Santosa, Hendrik; Jiyoun Hong, Melissa; Kim, Sung-Phil; Hong, Keum-Shik

2013-07-01

Functional near-infrared spectroscopy (fNIRS) is used to detect concentration changes of oxy-hemoglobin and deoxy-hemoglobin in the human brain. The main difficulty entailed in the analysis of fNIRS signals is the fact that the hemodynamic response to a specific neuronal activation is contaminated by physiological and instrument noises, motion artifacts, and other interferences. This paper proposes independent component analysis (ICA) as a means of identifying the original hemodynamic response in the presence of noises. The original hemodynamic response was reconstructed using the primary independent component (IC) and other, less-weighting-coefficient ICs. In order to generate experimental brain stimuli, arithmetic tasks were administered to eight volunteer subjects. The t-value of the reconstructed hemodynamic response was improved by using the ICs found in the measured data. The best t-value out of 16 low-pass-filtered signals was 37, and that of the reconstructed one was 51. Also, the average t-value of the eight subjects' reconstructed signals was 40, whereas that of all of their low-pass-filtered signals was only 20. Overall, the results showed the applicability of the ICA-based method to noise-contamination reduction in brain mapping.

Isolation and purification of antigenic components of Cryptococcus.

PubMed

Wozniak, Karen L; Levitz, Stuart M

2009-01-01

The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species.

Investigation of the 2f1-f2 and 2f2-f1 distortion product otoacoustic emissions using a computational model of the gerbil ear.

PubMed

Wen, Haiqi; Bowling, Thomas; Meaud, Julien

2018-05-19

In this work, a three-dimensional computational model of the gerbil ear is used to investigate the generation of the 2f 1 -f 2 and 2f 2 -f 1 distortion product otoacoustic emissions (DPOAEs). In order to predict both the distortion and reflection sources, cochlear roughness is modeled by introducing random inhomogeneities in the outer hair cell properties. The model was used to simulate the generation of DPOAEs in response to a two-tone stimulus for various primary stimulus levels and frequency ratios. As in published experiments, the 2f 1 -f 2 DPOAEs are mostly dominated by the distortion component while the 2f 2 -f 1 DPOAEs are dominated by the reflection component; furthermore, the influence of the levels and frequency ratio of the primaries are consistent with measurements. Analysis of the intracochlear response shows that the distortion component has the highest magnitude at all longitudinal locations for the 2f 1 -f 2 distortion product (DP) while the distortion component only dominates close to the DP best place in the case of the 2f 2 -f 1 DP. Decomposition of the intracochlear DPs into forward and reverse waves demonstrates that the 2f 1 -f 2 DP generates reverse waves for both the distortion and reflection components; however, a reverse wave is only generated for the reflection component in the case of the 2f 2 -f 1 DP. As in experiments in the gerbil, the group delay of the reflection component of the DPOAE is between 1× and 2× the forward group delay, which is consistent with the propagation of DP towards the stapes as slow reverse waves. Copyright © 2018 Elsevier B.V. All rights reserved.

The slow inward calcium current is responsible for a part of the contraction of patch-clamped rat myoballs.

PubMed

Rivet, M; Cognard, C; Raymond, G

1989-01-01

The slow inward calcium current and the contractile response were simultaneously recorded in voltage clamped (whole cell patch clamp recording) rat myoballs in primary culture. The shape of the contraction(T)/potential(V) relationship and the application of the inorganic calcium channel blocker cadmium (1.5 mM), which suppresses a part of the contractile activity, demonstrate the existence of two components of contraction. One of them is related to the slow calcium current.

Dengue Virus Activates Polyreactive, Natural IgG B Cells after Primary and Secondary Infection

PubMed Central

Toh, Ying Xiu; Flamand, Marie; Devi, Shamala; Koh, Mickey B.; Hibberd, Martin L.; Ooi, Eng Eong; Low, Jenny G.; Leo, Yee Sin; Gu, Feng; Fink, Katja

2011-01-01

Background Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection. Methodology/Principal Findings We assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4–7 days after fever onset was more than 50% even after primary infection. Conclusions/Significance Poly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and “innate specificities” seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development. PMID:22216280

A framework for conducting mechanistic based reliability assessments of components operating in complex systems

NASA Astrophysics Data System (ADS)

Wallace, Jon Michael

2003-10-01

Reliability prediction of components operating in complex systems has historically been conducted in a statistically isolated manner. Current physics-based, i.e. mechanistic, component reliability approaches focus more on component-specific attributes and mathematical algorithms and not enough on the influence of the system. The result is that significant error can be introduced into the component reliability assessment process. The objective of this study is the development of a framework that infuses the needs and influence of the system into the process of conducting mechanistic-based component reliability assessments. The formulated framework consists of six primary steps. The first three steps, identification, decomposition, and synthesis, are primarily qualitative in nature and employ system reliability and safety engineering principles to construct an appropriate starting point for the component reliability assessment. The following two steps are the most unique. They involve a step to efficiently characterize and quantify the system-driven local parameter space and a subsequent step using this information to guide the reduction of the component parameter space. The local statistical space quantification step is accomplished using two proposed multivariate probability models: Multi-Response First Order Second Moment and Taylor-Based Inverse Transformation. Where existing joint probability models require preliminary distribution and correlation information of the responses, these models combine statistical information of the input parameters with an efficient sampling of the response analyses to produce the multi-response joint probability distribution. Parameter space reduction is accomplished using Approximate Canonical Correlation Analysis (ACCA) employed as a multi-response screening technique. The novelty of this approach is that each individual local parameter and even subsets of parameters representing entire contributing analyses can now be rank ordered with respect to their contribution to not just one response, but the entire vector of component responses simultaneously. The final step of the framework is the actual probabilistic assessment of the component. Although the same multivariate probability tools employed in the characterization step can be used for the component probability assessment, variations of this final step are given to allow for the utilization of existing probabilistic methods such as response surface Monte Carlo and Fast Probability Integration. The overall framework developed in this study is implemented to assess the finite-element based reliability prediction of a gas turbine airfoil involving several failure responses. Results of this implementation are compared to results generated using the conventional 'isolated' approach as well as a validation approach conducted through large sample Monte Carlo simulations. The framework resulted in a considerable improvement to the accuracy of the part reliability assessment and an improved understanding of the component failure behavior. Considerable statistical complexity in the form of joint non-normal behavior was found and accounted for using the framework. Future applications of the framework elements are discussed.

From concept to content: assessing the implementation fidelity of a chronic care model for frail, older people who live at home.

PubMed

Muntinga, Maaike E; Van Leeuwen, Karen M; Schellevis, François G; Nijpels, Giel; Jansen, Aaltje P D

2015-01-22

Implementation fidelity, the degree to which a care program is implemented as intended, can influence program impact. Since results of trials that aim to implement comprehensive care programs for frail, older people have been conflicting, assessing implementation fidelity alongside these trials is essential to differentiate between flaws inherent to the program and implementation issues. This study demonstrates how a theory-based assessment of fidelity can increase insight in the implementation process of a complex intervention in primary elderly care. The Geriatric Care Model was implemented among 35 primary care practices in the Netherlands. During home visits, practice nurses conducted a comprehensive geriatric assessment and wrote a tailored care plan. Multidisciplinary team consultations were organized with the aim to enhance the coordination between professionals caring for a single patient with complex needs. To assess fidelity, we identified 5 key intervention components and formulated corresponding research questions using Carroll's framework for fidelity. Adherence (coverage, frequency, duration, content) was assessed per intervention component during and at the end of the intervention period. Two moderating factors (participant responsiveness and facilitation strategies) were assessed at the end of the intervention. Adherence to the geriatric assessments and care plans was high, but decreased over time. Adherence to multidisciplinary consultations was initially poor, but increased over time. We found that individual differences in adherence between practice nurses and primary care physicians were moderate, while differences in participant responsiveness (satisfaction, involvement) were more distinct. Nurses deviated from protocol due to contextual factors and personal work routines. Adherence to the Geriatric Care Model was high for most of the essential intervention components. Study limitations include the limited number of assessed moderating factors. We argue that a longitudinal investigation of adherence per intervention component is essential for a complete understanding of the implementation process, but that such investigations may be complicated by practical and methodological challenges. The Netherlands National Trial Register (NTR). 2160 .

Secondary Prevention Efforts at the Middle School Level: An Application of the Behavior Education Program

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Capizzi, Andrea M.; Fisher, Marisa H.; Ennis, Robin Parks

2012-01-01

In this study we examine the impact of the Behavior Education Program (BEP; Hawken, MacLeod, & Rawlings, 2007) with four middle school students who were not responsive to a comprehensive primary prevention program including academic, behavioral and social components. To extend this line of inquiry we (a) conducted a functional behavioral…

Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.

ClinicalTrials.gov

2010-08-02

Ovarian; Melanoma; Renal; Prostate; Colorectal; Endometrial Carcinoma; Cervical Carcinoma; Testicular Cancer; Thyroid Cancer; Small Cell Lung Carcinoma; Mesothelioma; Breast Carcinoma; Esophageal Carcinoma; Gastric Cancer; Pancreatic Carcinoma; Neuroendocrine Cancer; Liver Cancer; Gallbladder Cancer; Biliary Tract Cancer; Anal Carcinoma; Bone Sarcomas; Soft Tissue Sarcomas; Carcinoma of Unknown Origin, Primary

Trophic dynamics of deep-sea megabenthos are mediated by surface productivity.

PubMed

Tecchio, Samuele; van Oevelen, Dick; Soetaert, Karline; Navarro, Joan; Ramírez-Llodra, Eva

2013-01-01

Most deep-sea benthic ecosystems are food limited and, in the majority of cases, are driven by the organic matter falling from the surface or advected downslope. Species may adapt to this scarceness by applying a wide variety of responses, such as feeding specialisation, niche width variation, and reduction in metabolic rates. The Mediterranean Sea hosts a gradient of food availability at the deep seafloor over its wide longitudinal transect. In the Mediterranean, broad regional studies on trophic habits are almost absent, and the response of deep-sea benthos to different trophic conditions is still speculative. Here, we show that both primary and secondary production processes taking place at surface layers are key drivers of deep-sea food web structuring. By employing an innovative statistical tool, we interpreted bulk-tissue δ(13)C and δ(15)N isotope ratios in benthic megafauna, and associated surface and mesopelagic components from the 3 basins of the Mediterranean Sea at 3 different depths (1200, 2000, and 3000 m). The trophic niche width and the amplitude of primary carbon sources were positively correlated with both primary and secondary surface production indicators. Moreover, mesopelagic organic matter utilization processes showed an intermediate position between surface and deep benthic components. These results shed light on the understanding of deep-sea ecosystems functioning and, at the same time, they demand further investigation.

Trophic Dynamics of Deep-Sea Megabenthos Are Mediated by Surface Productivity

PubMed Central

Tecchio, Samuele; van Oevelen, Dick; Soetaert, Karline; Navarro, Joan; Ramírez-Llodra, Eva

2013-01-01

Most deep-sea benthic ecosystems are food limited and, in the majority of cases, are driven by the organic matter falling from the surface or advected downslope. Species may adapt to this scarceness by applying a wide variety of responses, such as feeding specialisation, niche width variation, and reduction in metabolic rates. The Mediterranean Sea hosts a gradient of food availability at the deep seafloor over its wide longitudinal transect. In the Mediterranean, broad regional studies on trophic habits are almost absent, and the response of deep-sea benthos to different trophic conditions is still speculative. Here, we show that both primary and secondary production processes taking place at surface layers are key drivers of deep-sea food web structuring. By employing an innovative statistical tool, we interpreted bulk-tissue δ13C and δ15N isotope ratios in benthic megafauna, and associated surface and mesopelagic components from the 3 basins of the Mediterranean Sea at 3 different depths (1200, 2000, and 3000 m). The trophic niche width and the amplitude of primary carbon sources were positively correlated with both primary and secondary surface production indicators. Moreover, mesopelagic organic matter utilization processes showed an intermediate position between surface and deep benthic components. These results shed light on the understanding of deep-sea ecosystems functioning and, at the same time, they demand further investigation. PMID:23691098

Relationships between drought, heat and air humidity responses revealed by transcriptome-metabolome co-analysis.

PubMed

Georgii, Elisabeth; Jin, Ming; Zhao, Jin; Kanawati, Basem; Schmitt-Kopplin, Philippe; Albert, Andreas; Winkler, J Barbro; Schäffner, Anton R

2017-07-10

Elevated temperature and reduced water availability are frequently linked abiotic stresses that may provoke distinct as well as interacting molecular responses. Based on non-targeted metabolomic and transcriptomic measurements from Arabidopsis rosettes, this study aims at a systematic elucidation of relevant components in different drought and heat scenarios as well as relationships between molecular players of stress response. In combined drought-heat stress, the majority of single stress responses are maintained. However, interaction effects between drought and heat can be discovered as well; these relate to protein folding, flavonoid biosynthesis and growth inhibition, which are enhanced, reduced or specifically induced in combined stress, respectively. Heat stress experiments with and without supplementation of air humidity for maintenance of vapor pressure deficit suggest that decreased relative air humidity due to elevated temperature is an important component of heat stress, specifically being responsible for hormone-related responses to water deprivation. Remarkably, this "dry air effect" is the primary trigger of the metabolomic response to heat. In contrast, the transcriptomic response has a substantial temperature component exceeding the dry air component and including up-regulation of many transcription factors and protein folding-related genes. Data level integration independent of prior knowledge on pathways and condition labels reveals shared drought and heat responses between transcriptome and metabolome, biomarker candidates and co-regulation between genes and metabolic compounds, suggesting novel players in abiotic stress response pathways. Drought and heat stress interact both at transcript and at metabolite response level. A comprehensive, non-targeted view of this interaction as well as non-interacting processes is important to be taken into account when improving tolerance to abiotic stresses in breeding programs. Transcriptome and metabolome may respond with different extent to individual stress components. Their contrasting behavior in response to temperature stress highlights that the protein folding machinery effectively shields the metabolism from stress. Disentangling the complex relationships between transcriptome and metabolome in response to stress is an enormous challenge. As demonstrated by case studies with supporting evidence from additional data, the large dataset provided in this study may assist in determining linked genetic and metabolic features as candidates for future mechanistic analyses.

Primary cooling check valve steam generator and loose parts events of November 1985

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

Not Available

1985-12-23

On November 10, 1985, a primary coolant check valve, CV-3-8, was opened for inspection. The valve flapper and mounting bracket were found to have become detached from the valve body and were resting in the bottom of the valve. Normally, the bracket is secured to the valve body with three studs and nuts. All three sets of studs, nuts and stud retainers were missing. As part of the effort to locate the missing valve parts, the primary side of the No. 2A steam generator was opened for inspection. Three cap screws and an associated locking bar used to secure certainmore » internals were found to be missing. In response, the Director, Reactor Engineering Department was assigned lead responsibility for developing and directing the implementation of a plan to correct deficiencies and ready the plant to return to operation. Next, a Special Safety Assessment Team was established to provide a structured assessment of the safety aspect of the component failures and the implications of such failures to other components in the primary coolant system. This structured assessment was to result in the development of an action plan that included the development of specific safety criteria, and identification and conduct of special investigations and analyses required for recovery from the event. Finally, an independent Management Review Team was created. The purpose of this report is to document the work of the Management Review Team, including the causal factors analyses, and various reviews required to support the recovery process.« less

PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.

PubMed

McHugh, Anna; Robe, Amanda J; Palmer, Jeremy M; Jones, David E J

2006-05-01

Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression. Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects. T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans

PubMed Central

Popescu, Anda; Barlow, Steven; Venkatesan, Lalit; Wang, Jingyan; Popescu, Mihai

2014-01-01

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography, we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the right hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by Independent Component Analysis. Subsequent neuromagnetic source reconstruction identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e. SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the selective nature of these areas to respond predominantly to certain stimuli. PMID:22331631

Comprehensiveness of care from the patient perspective: comparison of primary healthcare evaluation instruments.

PubMed

Haggerty, Jeannie L; Beaulieu, Marie-Dominique; Pineault, Raynald; Burge, Frederick; Lévesque, Jean-Frédéric; Santor, Darcy A; Bouharaoui, Fatima; Beaulieu, Christine

2011-12-01

Comprehensiveness relates both to scope of services offered and to a whole-person clinical approach. Comprehensive services are defined as "the provision, either directly or indirectly, of a full range of services to meet most patients' healthcare needs"; whole-person care is "the extent to which a provider elicits and considers the physical, emotional and social aspects of a patient's health and considers the community context in their care." Among instruments that evaluate primary healthcare, two had subscales that mapped to comprehensive services and to the community component of whole-person care: the Primary Care Assessment Tool - Short Form (PCAT-S) and the Components of Primary Care Index (CPCI, a limited measure of whole-person care). To examine how well comprehensiveness is captured in validated instruments that evaluate primary healthcare from the patient's perspective. 645 adults with at least one healthcare contact in the previous 12 months responded to six instruments that evaluate primary healthcare. Scores were normalized for descriptive comparison. Exploratory and confirmatory (structural equation modelling) factor analysis examined fit to operational definition, and item response theory analysis examined item performance on common constructs. Over one-quarter of respondents had missing responses on services offered or doctor's knowledge of the community. The subscales did not load on a single factor; comprehensive services and community orientation were examined separately. The community orientation subscales did not perform satisfactorily. The three comprehensive services subscales fit very modestly onto two factors: (1) most healthcare needs (from one provider) (CPCI Comprehensive Care, PCAT-S First-Contact Utilization) and (2) range of services (PCAT-S Comprehensive Services Available). Individual item performance revealed several problems. Measurement of comprehensiveness is problematic, making this attribute a priority for measure development. Range of services offered is best obtained from providers. Whole-person care is not addressed as a separate construct, but some dimensions are covered by attributes such as interpersonal communication and relational continuity.

Emotions and health: findings from a randomized clinical trial on psychoeducational nursing to patients with implantable cardioverter defibrillator.

PubMed

Kikkenborg Berg, Selina; Støier, Louise; Moons, Philip; Zwisler, Ann-Dorthe; Winkel, Per; Ulrich Pedersen, Preben

2015-01-01

Serious illness will inevitably lead to a fundamental emotional reaction. Traditionally, in interventional treatment or rehabilitation trials, the psychological status of patients with implantable cardioverter defibrillators has been evaluated with anxiety and depression as outcome measures. In caring for these patients, the aim of nursing is to help patients manage life with complex heart disease. The early detection and management of negative emotional response might prevent the development of pathological conditions such as depression. The aims of this study were to (a) describe the trajectory of primary emotions over time in patients with implantable cardioverter defibrillators and (b) examine the potential effects of psychoeducational nursing on primary emotions. During the inclusion period (October 2007 to November 2009), 196 patients with implantable cardioverter defibrillator were randomized (1:1) to rehabilitation versus usual care. Rehabilitation consisted of a psychoeducational nursing component and an exercise training component. This article concerns phase 1, psychoeducational nursing, guided by a theory of nursing, Rosemary Rizzo Parses Human Becoming Practice Methodologies. The outcome measure is the Emotions and Health Scale. The scale consists of 8 primary emotions: joy, agreeableness, surprise, fear, sadness, disgust, anger, and anticipation. Mean (SD) age was 58 (13) years, and 79% of the participants were men. Significant improvements were found in primary emotional responses over time (P < .05) when combining groups. However, no difference in emotional intensity was found between the groups after 3 months of psychoeducational nursing intervention (P > .05). Primary emotions are affected after implantable cardioverter defibrillator implantation. Improvements over time were found. However, it was not possible to detect any effect of a short-term psychoeducational nursing intervention. Evaluating the primary emotions might be a good way for nurses to monitor patients' psychological outcomes because the instrument is sensitive to changes over a short period. Further development of early psychoeducational nursing interventions for patients with implantable cardioverter defibrillators is needed.

Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans.

PubMed

Qiu, Yunhai; Inui, Koji; Wang, Xiaohong; Nguyen, Binh Thi; Tran, Tuan Diep; Kakigi, Ryusuke

2004-03-01

Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region. Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model. (1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P < 0.01) and cingulate cortex (P < 0.001) were more sensitive than the SI (P < 0.05) and MT (P < 0.05). We confirmed that SI in the contralateral hemisphere and SII-insula, cingulate cortex and MT in bilateral hemispheres play a major role in second pain perception, and all sites were much affected by a change of attention, indicating that these regions are related to the cognitive aspect of second pain perception. The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.

[Health Index applied to the city of Araraquara, SP: an instrument to accompaniment the primary care].

PubMed

Mattos, Augustus Tadeu Relo de; Caccia-Bava, Maria do Carmo G G; Barbosa, Débora Cristina Modesto

2013-03-01

The improvement of the process of evaluation and monitoring of the Primary Care Attention has been yearned by the managers of the different spheres in the context of the Unified System Health - UHS. Thus, in the order to identify the conditions of the health assistance in the city of Araraquara/SP, based on the particular features presented in the inscribe areas of each unit of health. It was adopted by means of a composed indicator aiming to favor a broader view which contemplates the emergency of phenomena from a more including vision. It was used the methodology developed in the Index of Health of Drumond Jr, whose final value of the Index is gotten by the average of the values of the components of each health district. To the components originally adopted - Coefficient of Infant Mortality, Coefficient of Tuberculosis Incidence, Coefficient of Mortality by External Causes and Coefficient of Precocious Mortality by Chronic Diseases - was still added in this study, the Tax of Alphabetization and the Monthly Nominal Average Income of Responsible People for the Domiciles. The 24 Units of Health had been classified according to values obtained in the relation among its components. The results point intra-urban differentials in relation to the majority of the components and lower values for the Health Units located at the periphery of the city. Knowing this fact municipal administration is of fundamental importance to progress in improving the process of evaluation of primary care in the county.

DPOAE generation dependence on primary frequencies ratio

NASA Astrophysics Data System (ADS)

Botti, Teresa; Sisto, Renata; Moleti, Arturo; D'Amato, Luisa; Sanjust, Filippo

2015-12-01

Two different mechanisms are responsible for the DPOAE generation. The nonlinear distortion wave-fixed mechanism generates the DPOAE Zero-Latency (ZL) component, as a backward traveling wave from the "overlap" region. Linear reflection of the forward DP wave (IDP) generates the DPOAE Long-Latency (LL) component through a place-fixed mechanism. ZL and LL components add up vectorially to generate the DPOAE recorded in the ear canal. The 2f1 - f2 and 2f2 - f1 DPOAE intensity depends on the stimulus level and on the primary frequency ratio r = f2/f1, where f1 and f2 are the primary stimuli frequencies. Here we study the behavior of the ZL and LL DPOAE components as a function of r by both numerical and laboratory experiments, measuring DPAOEs with an equal primary levels (L1 = L2) paradigm in the range [35, 75] dB SPL, with r ranging in [1.1, 1.45]. Numerical simulations of a nonlocal nonlinear model have been performed without cochlear roughness, to suppress the linear reflection mechanism. In this way the model solution at the base represents the DPOAE ZL component, and the solution at the corresponding DPOAE tonotopic place corresponds to the IDP. This technique has been not effectual to study the 2f2 - f1 DPOAE, as a consequence of its generation mechanism. While the 2f1 - f2 generation place is known to be the tonotopic place x(f2), the 2f2 - f1 DPOAE one has to be assumed basal to its corresponding reflection place. That is because ZL components generated in x(f2) cannot significantly pass through their resonant place. Moreover increasing the ratio r, 2f2 - f1 ZL and LL generation place approach each other, because the overlap region of primary tones decreases. Consequently, the distinction between the two places becomes complicated. DPOAEs have been measured in six young normal-hearing subjects. DPOAE ZL and LL components have been separated by a time-frequency filtering method based on the wavelet transform 1. due to their different phase gradient delay. Amplitude/phase vs ratio and ratio-frequency maps have been analyzed both in numerical and laboratory data. As already observed in animal studies [4], the generation of 2f1 - f2 DPOAE is around the f2 tonotopic place with a maximum around r = 1.2 for the ZL component, while the LL component shows a decreasing trend with r. Instead, 2f2 - f1 DPOAEs show a decreasing trend with r for both ZL and LL components.

Clinical features and management of primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in cirrhosis and need for liver transplantation and reduced life expectancy. The majority of cases occur in young and middle-aged men, often in association with inflammatory bowel disease. The etiology of primary sclerosing cholangitis includes immune-mediated components and elements of undefined nature. No effective medical therapy has been identified. The multiple complications of primary sclerosing cholangitis include metabolic bone disease, dominant strictures, bacterial cholangitis, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of primary sclerosing cholangitis. Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease, although recurrence in the allografted liver has been described. A PSC-like variant attracting attention is cholangitis marked by raised levels of the immunoglobulin G4 subclass, prominence of plasma cells within the lesions, and steroid responsiveness. PMID:18528931

Activated stress response pathways within multicellular aggregates utilize an autocrine component.

PubMed

Jack, Graham D; Cabrera, M Carla; Manning, Michael L; Slaughter, Stephen M; Potts, Malcolm; Helm, Richard F

2007-04-01

Multicellular aggregates (spheroids) of primary human foreskin fibroblasts (HFF-2) and a glioblastoma cell line (T98G) entered and exited from long term (2 weeks) metabolic arrest utilizing an autocrine response. Cytokine production (specifically IFN-gamma) activated a Gadd45alpha/p38 pathway that led to increased AP-1 (c-jun and ATF3) transcription factor levels, augmenting cytokine production in an autocrine fashion. Whereas HFF-2 aggregates were capable of surviving long term arrest and recovery during NF-kappaB inhibition independent of JNK activation, T98G aggregates were not. Such endogenous processes are not easily observed with adherent monolayer cell culturing systems, strongly suggesting that more emphasis needs to be placed on determining the operational signal transduction cascades within multicellular aggregates. Extracellular inputs such as spheroid formation, arrest, and regrowth as monolayers invoke intracellular signaling responses converging at the AP-1 transcription factor level. Variations in responses are both cell type and transformation state dependent and require an autocrine cytokine component. The data are discussed in relation to the wounding response and avascular tumor growth mechanisms.

Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: decreased emotional response versus increased top-down attention to nonemotional features.

PubMed

White, Stuart F; Marsh, Abigail A; Fowler, Katherine A; Schechter, Julia C; Adalio, Christopher; Pope, Kayla; Sinclair, Stephen; Pine, Daniel S; Blair, R James R

2012-07-01

Amygdala dysfunction has been reported to exist in youths and adults with psychopathic traits. However, there has been disagreement as to whether this dysfunction reflects a primary emotional deficit or is secondary to atypical attentional control. The authors examined the validity of the contrasting predictions. Participants were 15 children and adolescents (ages 10–17 years) with both disruptive behavior disorders and psychopathic traits and 17 healthy comparison youths. Functional MRI was used to assess the response of the amygdala and regions implicated in top-down attentional control (the dorsomedial and lateral frontal cortices) to emotional expression under conditions of high and low attentional load. Relative to youths with disruptive behavior disorders and psychopathic traits, healthy comparison subjects showed a significantly greater increase in the typical amygdala response to fearful expressions under low relative to high attentional load conditions. There was also a selective inverse relationship between the response to fearful expressions under low attentional load and the callous-unemotional component (but not the narcissism or impulsivity component) of psychopathic traits. In contrast, the two groups did not differ in the significant recruitment of the dorsomedial and lateral frontal cortices as a function of attentional load. Youths with disruptive behavior disorders and psychopathic traits showed reduced amygdala responses to fearful expressions under low attentional load but no indications of increased recruitment of regions implicated in top-down attentional control. These findings suggest that the emotional deficit observed in youths with disruptive behavior disorders and psychopathic traits is primary and not secondary to increased top-down attention to nonemotional stimulus features.

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

PubMed

Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

2017-07-01

Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. Copyright © 2017 American Society for Microbiology.

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia

PubMed Central

Peterson, Christopher W.; Kiem, Hans-Peter

2017-01-01

ABSTRACT Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the “Berlin patient” remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. PMID:28404854

Compression strength of composite primary structural components

NASA Technical Reports Server (NTRS)

Johnson, Eric R.

1993-01-01

Two projects are summarized. The first project is entitled 'Stiffener Crippling Inititated by Delaminations' and its objective is to develop a computational model of the stiffener specimens that includes the capability to predict the interlaminar stress response at the flange free edge in postbuckling. The second is entitled 'Pressure Pillowing of an Orthogonally Stiffened Cylindrical Shell'. A paper written on this project is included.

Avian response to pine restoration at Peck Ranch Conservation Area

Treesearch

Richard Clawson; Carrie Steen; Kim Houf; Terry Thompson

2007-01-01

Midco Pine Flats is a 2,223-acre region of Peck Ranch Conservation Area (CA) that is classified as a pine-oak plains land type association. Extensive logging in the early 1900s removed most overstory shortleaf pine allowing oak to become the primary overstory component. In 2000, Missouri Department of Conservation staff initiated a pineoak woodland restoration project...

Transforming Joint Warfighting Capabilities

DTIC Science & Technology

2004-01-01

Certification guidance covers Internet or Web compatibility and the layout to include window size, color, typography , and graphic format. Further require...developed the JMF concept, defined as a package of 20,000 personnel from designated component ready forces. It is aug- mented by supporting commands...trust and confidence in joint warfighting. PACOM established standing com- mand and control relationships for cri- sis response by designating primary

Glutamate-Mediated Primary Somatosensory Cortex Excitability Correlated with Circulating Copper and Ceruloplasmin

PubMed Central

Tecchio, Franca; Assenza, Giovanni; Zappasodi, Filippo; Mariani, Stefania; Salustri, Carlo; Squitti, Rosanna

2011-01-01

Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20) of the somatosensory magnetic fields (SEFs) evoked by right median nerve stimulation at wrist. Method. Thirty healthy right-handed subjects (51 ± 22 years) were enrolled in the study. A source reconstruction algorithm was applied to assess the amount of synchronously activated neurons subtending the M20 and the following SEF component (M30), which is generated by two independent contributions of gabaergic and glutamatergic transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin saturation, and zinc levels were measured. Results. Total copper and ceruloplasmin negatively correlated with the M20 source strength. Conclusion. This pilot study suggests that higher level of body copper reserve, as marked by ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness. PMID:22145081

The Myriad Properties of Pasteurella multocida Lipopolysaccharide

PubMed Central

Harper, Marina; Boyce, John Dallas

2017-01-01

Pasteurella multocida is a heterogeneous species that is a primary pathogen of many different vertebrates. This Gram-negative bacterium can cause a range of diseases, including fowl cholera in birds, haemorrhagic septicaemia in ungulates, atrophic rhinitis in swine, and lower respiratory tract infections in cattle and pigs. One of the primary virulence factors of P. multocida is lipopolysaccharide (LPS). Recent work has shown that this crucial surface molecule shows significant structural variability across different P. multocida strains, with many producing LPS structures that are highly similar to the carbohydrate component of host glycoproteins. It is likely that this LPS mimicry of host molecules plays a major role in the survival of P. multocida in certain host niches. P. multocida LPS also plays a significant role in resisting the action of chicken cathelicidins, and is a strong stimulator of host immune responses. The inflammatory response to the endotoxic lipid A component is a major contributor to the pathogenesis of certain infections. Recent work has shown that vaccines containing killed bacteria give protection only against other strains with identical, or nearly identical, surface LPS structures. Conversely, live attenuated vaccines give protection that is broadly protective, and their efficacy is independent of LPS structure. PMID:28825691

[Characteristics of extracranial malignant germ cell tumours in two age groups of children (0-10 and 10-18 years). Multicentre experiences].

PubMed

Drozyńska, Elzbieta; Połczyńska, Katarzyna; Popadiuk, Stefan; Niedzwiecki, Maciej; Wiśniewski, Jakub; Balcerska, Anna; Izycka-Swieszewska, Ewa; Bilska, Katarzyna; Balwierz, Walentyna; Chełmecka, Lilianna; Chybicka, Alicja; Dudeńko, Izabella; Karolczyk, Grazyna; Kowalczyk, Jerzy; Krawczuk-Rybak, Maryna; Kurylak, Andrzej; Leszczyńska, Elzbieta; Matysiak, Michał; Młynarski, Wojciech; Pobudejska, Aneta; Sobol, Grazyna; Sońta-Jakimczyk, Danuta; Szajdak, Katarzyna; Tredowska-Skoczeń, Dorota; Szmyd, Krzysztof; Trelińska, Joanna; Urasiński, Tomasz; Wachowiak, Jacek; Wieczorek, Maria; Wiśniewska-Slusarz, Hanna; Woźniak, Sebastian; Woźniak, Wojciech; Wysocki, Mariusz

2011-01-01

In order to assess if any differences exist in children germ cell tumours depending on age, we compared some features of germ cell tumours in two age groups:younger than 10 and between 11 and 18 years. Data of 146 patients with germ cell tumours treated in 15 Polish paediatric oncology departments between 1995 and 2005 were evaluated. They were divided into two groups: 76 children 0-10 years old (group I) and 70 patients 11-18 years old (group II). Tumour morphology, sex of patients, primary tumour and metastases localization, disease stage, biochemical markers, treatment response, disease relapse and long survival were analyzed. Every patient was treated according to the TGM 95 protocol. In group 1, 67 tumours were assessed histologically. 64%t tumours had homogenous structure with yolk sac tumour in predominance and 36% were mixed. Yolk sac tumour (YST) or teratoma as components of mixed tumours were the most commonly found. In older group 64 tumours were examined, 41% were homogenous, and seminoma/dysgerminoma predominated. In 59% mixed tumours the most common components were YST embryonal carcinoma and teratoma. The most common primary site in group I was the sacrococcygeal region while in group II - the gonads. Disseminated disease was recognized mostly in older children. Among two evaluated serum markers, AFP was increased mostly in younger patients (76% vs 44%), and 3HCG in older group (40% vs 9%). Treatment response was comparable in both groups. Two relapses were observed in each group. Poor outcome was noted in 17/140 analyzed patients: 9 (12%) in group I and 8 (11%) in group II. In 12 of patients with poor outcome the cause of death was progression and in 5 of them - treatment complications. 1. Germ cell tumours in younger and older children differ in histology, primary localization and serum level of biochemical markers. 2. In older patients germ cell tumours are recognized more frequently in advanced clinical stages. 3. Treatment response was comparable in both groups. 4. There is a need to analyze the intensity of chemotherapy to precise the adequate risk groups according to primary treatment response.

Does engagement with exposure yield better outcomes? Components of presence as a predictor of treatment response for virtual reality exposure therapy for social phobia.

PubMed

Price, Matthew; Mehta, Natasha; Tone, Erin B; Anderson, Page L

2011-08-01

Virtual reality exposure (VRE) has been shown to be effective for treating a variety of anxiety disorders, including social phobia. Presence, or the level of connection an individual feels with the virtual environment, is widely discussed as a critical construct both for the experience of anxiety within a virtual environment and for a successful response to VRE. Two published studies show that whereas generalized presence relates to fear ratings during VRE, it does not relate to treatment response. However, presence has been conceptualized as multidimensional, with three primary factors (spatial presence, involvement, and realness). These factors can be linked to other research on the facilitation of fear during exposure, inhibitors of treatment response (e.g., distraction), and more recent theoretical discussions of the mechanisms of exposure therapy, such as Bouton's description of expectancy violation. As such, one or more of these components of presence may be more strongly associated with the experience of fear during VRE and treatment response than the overarching construct. The current study (N=41) evaluated relations between three theorized components of presence, fear ratings during VRE, and treatment response for VRE for social phobia. Results suggest that total presence and realness subscale scores were related to in-session peak fear ratings. However, only scores on the involvement subscale significantly predicted treatment response. Implications of these findings are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Does engagement with exposure yield better outcomes? Components of presence as a predictor of treatment response for virtual reality exposure therapy for social phobia

PubMed Central

Price, Matthew; Mehta, Natasha; Tone, Erin B.; Anderson, Page L.

2012-01-01

Virtual reality exposure (VRE) has been shown to be effective for treating a variety of anxiety disorders, including social phobia. Presence, or the level of connection an individual feels with the virtual environment, is widely discussed as a critical construct both for the experience of anxiety within a virtual environment and for a successful response to VRE. Two published studies show that whereas generalized presence relates to fear ratings during VRE, it does not relate to treatment response. However, presence has been conceptualized as multidimensional, with three primary factors (spatial presence, involvement, and realness). These factors can be linked to other research on the facilitation of fear during exposure, inhibitors of treatment response (e.g., distraction), and more recent theoretical discussions of the mechanisms of exposure therapy, such as Bouton’s description of expectancy violation. As such, one or more of these components of presence may be more strongly associated with the experience of fear during VRE and treatment response than the overarching construct. The current study (N = 41) evaluated relations between three theorized components of presence, fear ratings during VRE, and treatment response for VRE for social phobia. Results suggest that total presence and realness subscale scores were related to in-session peak fear ratings. However, only scores on the involvement subscale significantly predicted treatment response. Implications of these findings are discussed. PMID:21515027

Inbreeding effects on immune response in free-living song sparrows (Melospiza melodia).

PubMed

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Elliott, Kyle H; Sampson, Laura; Hasselquist, Dennis

2007-03-07

The consequences of inbreeding for host immunity to parasitic infection have broad implications for the evolutionary and dynamical impacts of parasites on populations where inbreeding occurs. To rigorously assess the magnitude and the prevalence of inbreeding effects on immunity, multiple components of host immune response should be related to inbreeding coefficient (f) in free-living individuals. We used a pedigreed, free-living population of song sparrows (Melospiza melodia) to test whether individual responses to widely used experimental immune challenges varied consistently with f. The patagial swelling response to phytohaemagglutinin declined markedly with f in both females and males in both 2002 and 2003, although overall inbreeding depression was greater in males. The primary antibody response to tetanus toxoid declined with f in females but not in males in both 2004 and 2005. Primary antibody responses to diphtheria toxoid were low but tended to decline with f in 2004. Overall inbreeding depression did not solely reflect particularly strong immune responses in outbred offspring of immigrant-native pairings or weak responses in highly inbred individuals. These data indicate substantial and apparently sex-specific inbreeding effects on immune response, implying that inbred hosts may be relatively susceptible to parasitic infection to differing degrees in males and females.

Antibody persistence of two pentavalent DTwP-HB-Hib vaccines to the age of 15-18 months, and response to the booster dose of quadrivalent DTwP-Hib vaccine.

PubMed

Sharma, Hitt; Yadav, Sangeeta; Lalwani, Sanjay; Kapre, Subhash; Jadhav, Suresh; Parekh, Sameer; Palkar, Sonali; Ravetkar, Satish; Bahl, Sunil; Kumar, Rakesh; Shewale, Sunil

2013-01-07

Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive(®) of Panacea Biotec), and response to the booster dose of DTwP-Hib (Quadrovax(®)) vaccine. Children who completed their primary immunization were assessed for antibodies at 15-18 months of age, and then given a booster dose of DTwP-Hib vaccine. Reactogenicity and safety of the booster dose was evaluated. Both pentavalent vaccines demonstrated a good immune response at 15-18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ~78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose. Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP-Hib (Quadrovax(®)) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac(®)). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax(®)) administered as booster dose was acceptable. Copyright © 2012 Elsevier Ltd. All rights reserved.

Semiochemical-mediated flight responses of sap beetle vectors of oak wilt, Ceratocystis fagacearum.

PubMed

Kyhl, John F; Bartelt, Robert J; Cossé, Allard; Juzwik, Jennifer; Seybold, Steven J

2002-08-01

The sap beetle, Colopterus truncatus (Coleoptera: Nitidulidae), is one of the primary vectors of the oak wilt pathogen, Ceratocystis fagacearum, in the north-central United States. Field behavioral assays utilizing various release rates and blends of three methyl-branched hydrocarbon aggregation pheromone components showed that flight responses of this beetle were similar in Illinois and Minnesota populations. In both locations, both sexes of the beetle responded synergistically to a combination of the three-component pheromone and fermenting whole-wheat bread dough. Further, Colopterus truncatus preferred a high release rate over a low release rate of the three-component blend. In both locations, the response of C. truncatus to a simplified version of the pheromone consisting of (2E,4E,6E)-3,5-dimethyl-2,4,6-octatriene (1) and (2E,4E,6E,8E)-3,5,7-trimethyl-2,4,6,8-decatetraene (3) was not significantly different from the response to the three-component blend. An experiment in Illinois with all possible combinations of the components demonstrated that the decatetraene (3) was the crucial component in the blend; of all treatments, the maximal response was elicited by 3 + dough. Chipped bark, phloem, and xylem from northern pin oak, Quercus ellipsoidalis, was not attractive to C. truncatus in Minnesota. During a weekly survey over two seasons in Minnesota, C. truncatus flew in response to the three-component pheromone between early April and early July, with the maximum responses coming on May 4, 2000 and April 20, 2001. During both years, more than 98% of the beetles were trapped between April 14 and June 1. During the same survey, Glischrochilus spp. (Nitiduildae) flew during longer periods of the summer, particularly in 2001. The sex ratio of C. truncatus responding during all experiments was female-biased (1.8:1, female-male), which is characteristic of other male-produced coleopteran aggregation pheromones. Other sap beetles that play a minor role in the pathobiology of C. fagacearum also responded in experiments conducted in Minnesota. Carpophilus brachypterus Say was cross-attracted to the two- and three-component blends of the C. truncatus pheromone and dough, whereas two Glischrochilus spp. were attracted to all treatments that contained dough.

Left ventricular remodelling in chronic primary mitral regurgitation: implications for medical therapy.

PubMed

McCutcheon, Keir; Manga, Pravin

Surgical repair or replacement of the mitral valve is currently the only recommended therapy for severe primary mitral regurgitation. The chronic elevation of wall stress caused by the resulting volume overload leads to structural remodelling of the muscular, vascular and extracellular matrix components of the myocardium. These changes are initially compensatory but in the long term have detrimental effects, which ultimately result in heart failure. Understanding the changes that occur in the myocardium due to volume overload at the molecular and cellular level may lead to medical interventions, which potentially could delay or prevent the adverse left ventricular remodelling associated with primary mitral regurgitation. The pathophysiological changes involved in left ventricular remodelling in response to chronic primary mitral regurgitation and the evidence for potential medical therapy, in particular beta-adrenergic blockers, are the focus of this review.

Isolation and Purification of Antigenic Components of Cryptococcus

PubMed Central

Wozniak, Karen L.; Levitz, Stuart M.

2012-01-01

The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species. PMID:19089377

Expression of Antigen Processing and Presenting Molecules in Brain Metastasis of Breast Cancer

PubMed Central

Liu, Yan; Komohara, Yoshihiro; Domenick, Natalie; Ohno, Masasuke; Ikeura, Maki; Hamilton, Ronald L.; Horbinski, Craig; Wang, Xinhui; Ferrone, Soldano; Okada, Hideho

2012-01-01

Defects in human leukocyte antigen (HLA) class I antigen processing machinery (APM) component expression can have a negative impact on the clinical course of tumors and the response to T-cell-based immunotherapy. Since brain metastases of breast cancer are of increasing clinical significance, the APM component expression levels and CD8+ T-cell infiltration patterns were analyzed in primary breast and metastatic brain lesions of breast cancer by immunohistochemistry. Comparison of unpaired 50 primary and 33 brain metastases showed lower expression of β2-microgloblin, transporter associated with antigen processing (TAP) 1, TAP2 and calnexin in the brain lesions. Although no significant differences were found in APM component scores between primary breast and brain lesions in 15 paired cases, primary breast lesions of which patients eventually developed brain metastases showed lower levels of β2-microgloblin, TAP1 and calnexin compared with breast lesions without known brain metastases. The extent of CD8+ T cell infiltration was significantly higher in the lesions without metastasis compared with the ones with brain metastases, and was positively associated with the expression of TAP1 and calnexin. Furthermore, mouse tumor cells stably transfected with silencing hairpin (sh)RNA for TAP1 demonstrated a decreased susceptibility to cytotoxic T lymphocytes (CTL) in vitro and enhanced spontaneous brain metastasis in vivo. These data support the functional significance of TAP1 expression in tumor cells. Taken together, our data suggest that patients with low or defective TAP1 or calnexin in primary breast cancers may be at higher risks for developing brain metastasis due to the defects in T cell-based immunosurveillance. PMID:22065046

Assembly and Immunological Processing of Polyelectrolyte Multilayers Composed of Antigens and Adjuvants.

PubMed

Chiu, Yu-Chieh; Gammon, Joshua M; Andorko, James I; Tostanoski, Lisa H; Jewell, Christopher M

2016-07-27

While biomaterials provide a platform to control the delivery of vaccines, the recently discovered intrinsic inflammatory characteristics of many polymeric carriers can also complicate rational design because the carrier itself can alter the response to other vaccine components. To address this challenge, we recently developed immune-polyelectrolyte multilayer (iPEMs) capsules electrostatically assembled entirely from peptide antigen and molecular adjuvants. Here, we use iPEMs built from SIINFEKL model antigen and polyIC, a stimulatory toll-like receptor agonist, to investigate the impact of pH on iPEM assembly, the processing and interactions of each iPEM component with primary immune cells, and the role of these interactions during antigen-specific T cell responses in coculture and mice. We discovered that iPEM assembly is pH dependent with respect to both the antigen and adjuvant component. Controlling the pH also allows tuning of the relative loading of SIINFEKL and polyIC in iPEM capsules. During in vitro studies with primary dendritic cells (DCs), iPEM capsules ensure that greater than 95% of cells containing at least one signal (i.e., antigen, adjuvant) also contained the other signal. This codelivery leads to DC maturation and SIINFEKL presentation via the MHC-I antigen presentation pathway, resulting in antigen-specific T cell proliferation and pro-inflammatory cytokine secretion. In mice, iPEM capsules potently expand antigen-specific T cells compared with equivalent admixed formulations. Of note, these enhancements become more pronounced with successive booster injections, suggesting that iPEMs functionally improve memory recall response. Together our results reveal some of the features that can be tuned to modulate the properties of iPEM capsules, and how these modular vaccine structures can be used to enhance interactions with immune cells in vitro and in mice.

The Response of a Mechanical Oscillator Due to Swept and Dithered Excitation

NASA Technical Reports Server (NTRS)

Davis, R. Benjamin; Durham, R. Caitlyn; Brown, Andrew M.

2010-01-01

A single degree-of-freedom oscillator subject to linearly swept and/or dithered excitation is considered. Dither refers to the variation of an excitation frequency about a given nominal, or primary, frequency. Dither in rocket engine turbopump shaft speeds can be an important consideration when analyzing the dynamic response of turbomachinery components such as turbine blades. Results indicate that the incorporation of dithered excitation into a fatigue analysis may extend the predicted fatigue life of the structure by a factor of two or more.

Healthcare team training programs aimed at improving depression management in primary care: A systematic review.

PubMed

Vöhringer, Paul A; Castro, Ariel; Martínez, Pablo; Tala, Álvaro; Medina, Simón; Rojas, Graciela

2016-08-01

Although evidence from Latin America and the Caribbean suggests that depression can be effectively treated in primary care settings, depression management remains unevenly performed. This systematic review evaluates all the international evidence on healthcare team training programs aimed at improving the outcomes of patients with depression. Three databases were searched for articles in English or Spanish indexed up to November 20, 2014. Studies were included if they fulfilled the following conditions: clinical trials, meta-analyses, or systematic reviews; and if they evaluated a training or educational program intended to improve the management of depression by primary healthcare teams, and assessed change in depressive symptoms, diagnosis or response rates, referral rates, patients' satisfaction and/or quality of life, and the effectiveness of treatments. Nine studies were included in this systematic review. Five trials tested the effectiveness of multi-component interventions (training included), and the remaining studies evaluated the effectiveness of specific training programs for depression management. All the studies that implemented multi-component interventions were efficacious, and half of the training trials were shown to be effective. Contribution of training programs alone to the effectiveness of multi-component interventions is yet to be established. The lack of specificity regarding health providers' characteristics might be a confounding factor. The review conducted suggests that stand-alone training programs are less effective than multi-component interventions. In applying the evidence gathered from developed countries to Latin America and the Caribbean, these training programs must consider and address local conditions of mental health systems, and therefore multi-component interventions may be warranted. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of pedal rate on primary and slow-component oxygen uptake responses during heavy-cycle exercise.

PubMed

Pringle, Jamie S M; Doust, Jonathan H; Carter, Helen; Tolfrey, Keith; Jones, Andrew M

2003-04-01

We hypothesized that a higher pedal rate (assumed to result in a greater proportional contribution of type II motor units) would be associated with an increased amplitude of the O(2) uptake (Vo(2)) slow component during heavy-cycle exercise. Ten subjects (mean +/- SD, age 26 +/- 4 yr, body mass 71.5 +/- 7.9 kg) completed a series of square-wave transitions to heavy exercise at pedal rates of 35, 75, and 115 rpm. The exercise power output was set at 50% of the difference between the pedal rate-specific ventilatory threshold and peak Vo(2), and the baseline power output was adjusted to account for differences in the O(2) cost of unloaded pedaling. The gain of the Vo(2) primary component was significantly higher at 35 rpm compared with 75 and 115 rpm (mean +/- SE, 10.6 +/- 0.3, 9.5 +/- 0.2, and 8.9 +/- 0.4 ml. min(-1). W(-1), respectively; P < 0.05). The amplitude of the Vo(2) slow component was significantly greater at 115 rpm (328 +/- 29 ml/min) compared with 35 rpm (109 +/- 30 ml/min) and 75 rpm (202 +/- 38 ml/min) (P < 0.05). There were no significant differences in the time constants or time delays associated with the primary and slow components across the pedal rates. The change in blood lactate concentration was significantly greater at 115 rpm (3.7 +/- 0.2 mM) and 75 rpm (2.8 +/- 0.3 mM) compared with 35 rpm (1.7 +/- 0.4 mM) (P < 0.05). These data indicate that pedal rate influences Vo(2) kinetics during heavy exercise at the same relative intensity, presumably by altering motor unit recruitment patterns.

Field-quantified responses of tropical rainforest aboveground productivity to increasing CO2 and climatic stress, 1997-2009

NASA Astrophysics Data System (ADS)

Clark, Deborah A.; Clark, David B.; Oberbauer, Steven F.

2013-06-01

A directional change in tropical-forest productivity, a large component in the global carbon budget, would affect the rate of increase in atmospheric carbon dioxide ([CO2]). One current hypothesis is that "CO2 fertilization" has been increasing tropical forest productivity. Some lines of evidence instead suggest climate-driven productivity declines. Relevant direct field observations remain extremely limited for this biome. Using a unique long-term record of annual field measurements, we assessed annual aboveground net primary productivity (ANPP) and its relation to climatic factors and [CO2] in a neotropical rainforest through 1997-2009. Over this 12 year period, annual productivity did not increase, as would be expected with a dominant CO2 fertilization effect. Instead, the negative responses of ANPP components to climatic stress far exceeded the small positive responses associated with increasing [CO2]. Annual aboveground biomass production was well explained (73%) by the independent negative effects of increasing minimum temperatures and greater dry-season water stress. The long-term records enable a first field-based estimate of the [CO2] response of tropical forest ANPP: 5.24 g m-2 yr-1 yr-1 (the summed [CO2]-associated increases in two of the four production components; the largest component, leaf litterfall, showed no [CO2] association). If confirmed by longer data series, such a small response from a fertile tropical rainforest would indicate that current global models overestimate the benefits from CO2 fertilization for this biome, where most forests' poorer nutrient status more strongly constrains productivity responses to increasing [CO2]. Given the rapidly intensifying warming across tropical regions, tropical forest productivity could sharply decline through coming decades.

The Nitrate Transporter MtNPF6.8 (MtNRT1.3) Transports Abscisic Acid and Mediates Nitrate Regulation of Primary Root Growth in Medicago truncatula1[W

PubMed Central

Pellizzaro, Anthoni; Clochard, Thibault; Cukier, Caroline; Bourdin, Céline; Juchaux, Marjorie; Montrichard, Françoise; Thany, Steeve; Raymond, Valérie; Planchet, Elisabeth; Morère-Le Paven, Marie-Christine

2014-01-01

Elongation of the primary root during postgermination of Medicago truncatula seedlings is a multigenic trait that is responsive to exogenous nitrate. A quantitative genetic approach suggested the involvement of the nitrate transporter MtNPF6.8 (for Medicago truncatula NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER Family6.8) in the inhibition of primary root elongation by high exogenous nitrate. In this study, the inhibitory effect of nitrate on primary root elongation, via inhibition of elongation of root cortical cells, was abolished in npf6.8 knockdown lines. Accordingly, we propose that MtNPF6.8 mediates nitrate inhibitory effects on primary root growth in M. truncatula. pMtNPF6.8:GUS promoter-reporter gene fusion in Agrobacterium rhizogenes-generated transgenic roots showed the expression of MtNPF6.8 in the pericycle region of primary roots and lateral roots, and in lateral root primordia and tips. MtNPF6.8 expression was insensitive to auxin and was stimulated by abscisic acid (ABA), which restored the inhibitory effect of nitrate in npf6.8 knockdown lines. It is then proposed that ABA acts downstream of MtNPF6.8 in this nitrate signaling pathway. Furthermore, MtNPF6.8 was shown to transport ABA in Xenopus spp. oocytes, suggesting an additional role of MtNPF6.8 in ABA root-to-shoot translocation. 15NO3−-influx experiments showed that only the inducible component of the low-affinity transport system was affected in npf6.8 knockdown lines. This indicates that MtNPF6.8 is a major contributor to the inducible component of the low-affinity transport system. The short-term induction by nitrate of the expression of Nitrate Reductase1 (NR1) and NR2 (genes that encode two nitrate reductase isoforms) was greatly reduced in the npf6.8 knockdown lines, supporting a role of MtNPF6.8 in the primary nitrate response in M. truncatula. PMID:25367858

RACLETTE: a model for evaluating the thermal response of plasma facing components to slow high power plasma transients. Part I: Theory and description of model capabilities

NASA Astrophysics Data System (ADS)

Raffray, A. René; Federici, Gianfranco

1997-04-01

RACLETTE (Rate Analysis Code for pLasma Energy Transfer Transient Evaluation), a comprehensive but relatively simple and versatile model, was developed to help in the design analysis of plasma facing components (PFCs) under 'slow' high power transients, such as those associated with plasma vertical displacement events. The model includes all the key surface heat transfer processes such as evaporation, melting, and radiation, and their interaction with the PFC block thermal response and the coolant behaviour. This paper represents part I of two sister and complementary papers. It covers the model description, calibration and validation, and presents a number of parametric analyses shedding light on and identifying trends in the PFC armour block response to high plasma energy deposition transients. Parameters investigated include the plasma energy density and deposition time, the armour thickness and the presence of vapour shielding effects. Part II of the paper focuses on specific design analyses of ITER plasma facing components (divertor, limiter, primary first wall and baffle), including improvements in the thermal-hydraulic modeling required for better understanding the consequences of high energy deposition transients in particular for the ITER limiter case.

Investigating the cell death mechanisms in primary prostate cancer cells using low-temperature plasma treatment

NASA Astrophysics Data System (ADS)

O'Connell, Deborah; Hirst, A. M.; Packer, J. R.; Simms, M. S.; Mann, V. M.; Frame, F. M.; Maitland, N. J.

2016-09-01

Atmospheric pressure plasmas have shown considerable promise as a potential cancer therapy. An atmospheric pressure plasma driven with kHz kV excitation, operated with helium and oxygen admixtures is used to investigate the interaction with prostate cancer cells. The cytopathic effect was verified first in two commonly used prostate cancer cell lines (BPH-1 and PC-3 cells) and further extended to examine the effects in paired normal and tumour prostate epithelial cells cultured directly from patient tissues. Through the formation of reactive species in cell culture media, and potentially other plasma components, we observed high levels of DNA damage, together with reduced cell viability and colony-forming ability. We observed differences in response between the prostate cell lines and primary cells, particularly in terms of the mechanism of cell death. The primary cells ultimately undergo necrotic cell death in both the normal and tumour samples, in the complete absence of apoptosis. In addition, we provide the first evidence of an autophagic response in primary cells. This work highlights the importance of studying primary cultures in order to gain a more realistic insight into patient efficacy. EPSRC EP/H003797/1 & EP/K018388/1, Yorkshire Cancer Research: YCR Y257PA.

Robot-assisted and conventional therapies produce distinct rehabilitative trends in stroke survivors.

PubMed

Valero-Cuevas, Francisco J; Klamroth-Marganska, Verena; Winstein, Carolee J; Riener, Robert

2016-10-11

Comparing the efficacy of alternative therapeutic strategies for the rehabilitation of motor function in chronically impaired individuals is often inconclusive. For example, a recent randomized clinical trial (RCT) compared robot-assisted vs. conventional therapy in 77 patients who had had chronic motor impairment after a cerebrovascular accident. While patients assigned to robotic therapy had greater improvements in the primary outcome measure (change in score on the upper extremity section of the Fugl-Meyer assessment), the absolute difference between therapies was small, which left the clinical relevance in question. Here we revisit that study to test whether the multidimensional rehabilitative response of these patients can better distinguish between treatment outcomes. We used principal components analysis to find the correlation of changes across seven outcome measures between the start and end of 8 weeks of therapy. Permutation tests verified the robustness of the principal components found. Each therapy in fact produces different rehabilitative trends of recovery across the clinical, functional, and quality of life domains. A rehabilitative trend is a principal component that quantifies the correlations among changes in outcomes with each therapy. These findings challenge the traditional emphasis of RCTs on using a single primary outcome measure to compare rehabilitative responses that are naturally multidimensional. This alternative approach to, and interpretation of, the results of RCTs may will lead to more effective therapies targeted for the multidimensional mechanisms of recovery. ClinicalTrials.gov number NCT00719433 . Registered July 17, 2008.

Remotely Sensed Northern Vegetation Response to Changing Climate: Growing Season and Productivity Perspective

NASA Technical Reports Server (NTRS)

Ganguly, S.; Park, Taejin; Choi, Sungho; Bi, Jian; Knyazikhin, Yuri; Myneni, Ranga

2016-01-01

Vegetation growing season and maximum photosynthetic state determine spatiotemporal variability of seasonal total gross primary productivity of vegetation. Recent warming induced impacts accelerate shifts on growing season and physiological status over Northern vegetated land. Thus, understanding and quantifying these changes are very important. Here, we first investigate how vegetation growing season and maximum photosynthesis state are evolved and how such components contribute on inter-annual variation of seasonal total gross primary productivity. Furthermore, seasonally different response of northern vegetation to changing temperature and water availability is also investigated. We utilized both long-term remotely sensed data to extract larger scale growing season metrics (growing season start, end and duration) and productivity (i.e., growing season summed vegetation index, GSSVI) for answering these questions. We find that regionally diverged growing season shift and maximum photosynthetic state contribute differently characterized productivity inter-annual variability and trend. Also seasonally different response of vegetation gives different view of spatially varying interaction between vegetation and climate. These results highlight spatially and temporally varying vegetation dynamics and are reflective of biome-specific responses of northern vegetation to changing climate.

[Components and assembly of RNA-induced silencing complex].

PubMed

Song, Xue-Mei; Yan, Fei; Du, Li-Xin

2006-06-01

Degradation of homologous RNA in RNA interference is carried out by functional RNA-induced silencing complex (RISC). RISC contains Dicer, Argonaute proein, siRNA and other components. Researching structures and functions of these components is primary important for understanding assembly and functional mechanism of RISC, as well as the whole RNAi pathway. Recent research works showed that Dicer, containing RNaseIII domain, is responsible for production of siRNA at the beginning of RNAi, and guarantees the stability of RISC intermediate in assembly process. As the core component of RISC, Argonaute protein functions as slicer to cleave target RNA and offers the binding site of siRNA in RISC assembly, which are depended on PIWI domain and PAZ domain separately. Although there is only one strand of siRNA that is the guider of RISC, the double stranded structural character of siRNA is determinant of RNAi. Except those, there are still other components with unknown functions in RISC. The knowledge about RISC components and assembly now, is basis of a presumed RISC assembly model.

Artifacts produced during electrical stimulation of the vestibular nerve in cats. [autonomic nervous system components of motion sickness

NASA Technical Reports Server (NTRS)

Tang, P. C.

1973-01-01

Evidence is presented to indicate that evoked potentials in the recurrent laryngeal, the cervical sympathetic, and the phrenic nerve, commonly reported as being elicited by vestibular nerve stimulation, may be due to stimulation of structures other than the vestibular nerve. Experiments carried out in decerebrated cats indicated that stimulation of the petrous bone and not that of the vestibular nerve is responsible for the genesis of evoked potentials in the recurrent laryngeal and the cervical sympathetic nerves. The phrenic response to electrical stimulation applied through bipolar straight electrodes appears to be the result of stimulation of the facial nerve in the facial canal by current spread along the petrous bone, since stimulation of the suspended facial nerve evoked potentials only in the phrenic nerve and not in the recurrent laryngeal nerve. These findings indicate that autonomic components of motion sickness represent the secondary reactions and not the primary responses to vestibular stimulation.

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans.

PubMed

Popescu, Elena Anda; Barlow, Steven M; Venkatesan, Lalit; Wang, Jingyan; Popescu, Mihai

2013-06-01

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography (MEG), we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by independent component analysis. Subsequent source reconstruction techniques identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e., SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC areas can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the tendency of these areas to respond selectively to certain stimuli. Copyright © 2011 Wiley Periodicals, Inc.

Benthic Biotic Response to Climate Changes over the Last 700,000 Years, the Sea of Japan: Ostracode Assemblages from Site U1427, IODP Expedition 346

NASA Astrophysics Data System (ADS)

Huang, H. H. M.; Yasuhara, M.; Iwatani, H.; Alvarez Zarikian, C. A.; Bassetti, M. A.; Sagawa, T.

2016-12-01

The Sea of Japan is a marginal sea, semi-enclosed by the Eurasian Continent, Korean Peninsula, Japanese Islands, and shallow straits (water depth < 130 m). Marginal seas are ideal natural laboratories to study biotic responses to large-scale paleoclimate-ocean mechanisms as they are typically sensitive to glacial/interglacial and stadial/interstadial cycles. The modern oceanographic setting in the Sea of Japan is characterized by the influx of the Tsushima Warm Current (TWC) from the East China Sea, and this setting was formed 1.7 My ago by tectonic subsidence of the Tsushima Strait. The Sea of Japan, therefore, is an interesting research subject for studying the biotic response to orbital-scale climate changes and benthic faunal development under the influence of TWC. Here we present 700,000-year record of benthic biotic response to the paleoceanographic changes in the southern Sea of Japan based on ostracode assemblage reconstruction at IODP Site U1427. Five local extinction events were caused by extreme bottom conditions (mainly oxygen depletion) during the Ice Age Terminations I, II, IV, V, and VII. Primary and secondary ostracode assemblages were revealed by Q-mode k-means clustering, CABFAC factor analysis, and non-metric multidimensional scaling. The primary ostracode components, characterized by Krithe sawanensis and Cytheropteron hyalinosa, broadly reflect glacial/interglacial and high-latitude insolation cycles. In contrast, a faunal shift determined by the secondary faunal components was driven by the TWC enhancement at 300 ka.

Inactivation of DNA-Binding Response Regulator Sak189 Abrogates β-Antigen Expression and Affects Virulence of Streptococcus agalactiae

PubMed Central

Rozhdestvenskaya, Anastasia S.; Totolian, Artem A.; Dmitriev, Alexander V.

2010-01-01

Background Streptococcus agalactiae is able to colonize numerous tissues employing different mechanisms of gene regulation, particularly via two-component regulatory systems. These systems sense the environmental stimuli and regulate expression of the genes including virulence genes. Recently, the novel two-component regulatory system Sak188/Sak189 was identified. In S. agalactiae genome, it was adjacent to the bac gene encoding for β-antigen, an important virulence factor. Methodology/Principal Findings In this study, the sak188 and sak189 genes were inactivated, and the functional role of Sak188/Sak189 two-component system in regulation of the β-antigen expression was investigated. It was demonstrated that both transcription of bac gene and expression of encoded β-antigen were controlled by Sak189 response regulator, but not Sak188 histidine kinase. It was also found that the regulation occurred at transcriptional level. Finally, insertional inactivation of sak189 gene, but not sak188 gene, significantly affected virulent properties of S. agalactiae. Conclusions/Significance Sak189 response regulator is necessary for activation of bac gene transcription. It also controls the virulent properties of S. agalactiae. Given that the primary functional role of Sak188/Sak189 two-component systems is a control of bac gene transcription, this system can be annotated as BgrR/S (bac gene regulatory system). PMID:20419089

[Role of school lunch in primary school education: a trial analysis of school teachers' views using an open-ended questionnaire].

PubMed

Inayama, T; Kashiwazaki, H; Sakamoto, M

1998-12-01

We tried to analyze synthetically teachers' view points associated with health education and roles of school lunch in primary education. For this purpose, a survey using an open-ended questionnaire consisting of eight items relating to health education in the school curriculum was carried out in 100 teachers of ten public primary schools. Subjects were asked to describe their view regarding the following eight items: 1) health and physical guidance education, 2) school lunch guidance education, 3) pupils' attitude toward their own health and nutrition, 4) health education, 5) role of school lunch in education, 6) future subjects of health education, 7) class room lesson related to school lunch, 8) guidance in case of pupil with unbalanced dieting and food avoidance. Subjects described their own opinions on an open-ended questionnaire response sheet. Keywords in individual descriptions were selected, rearranged and classified into categories according to their own meanings, and each of the selected keywords were used as the dummy variable. To assess individual opinions synthetically, a principal component analysis was then applied to the variables collected through the teachers' descriptions, and four factors were extracted. The results were as follows. 1) Four factors obtained from the repeated principal component analysis were summarized as; roles of health education and school lunch program (the first principal component), cooperation with nurse-teachers and those in charge of lunch service (the second principal component), time allocation for health education in home-room activity and lunch time (the third principal component) and contents of health education and school lunch guidance and their future plan (the fourth principal component). 2) Teachers regarded the role of school lunch in primary education as providing daily supply of nutrients, teaching of table manners and building up friendships with classmates, health education and food and nutrition education, and developing food preferences through eating lunch together with classmates. 3) Significant positive correlation was observed between "the teachers' opinion about the role of school lunch of providing opportunity to learn good behavior for food preferences through eating lunch together with classmates" and the first principal component "roles of health education and school lunch program" (r = 0.39, p < 0.01). The variable "the role of school lunch is health education and food and nutrition education" showed positive correlation with the principle component "cooperation with nurse-teachers and those in charge of lunch service" (r = 0.27, p < 0.01). Interesting relationships obtained were that teachers with longer educational experience tended to place importance in health education and food and nutrition education as the role of school lunch, and that male teachers regarded the roles of school lunch more importantly for future education in primary education than female teachers did.

Variability and Correlations in Primary Visual Cortical Neurons Driven by Fixational Eye Movements

PubMed Central

McFarland, James M.; Cumming, Bruce G.

2016-01-01

The ability to distinguish between elements of a sensory neuron's activity that are stimulus independent versus driven by the stimulus is critical for addressing many questions in systems neuroscience. This is typically accomplished by measuring neural responses to repeated presentations of identical stimuli and identifying the trial-variable components of the response as noise. In awake primates, however, small “fixational” eye movements (FEMs) introduce uncontrolled trial-to-trial differences in the visual stimulus itself, potentially confounding this distinction. Here, we describe novel analytical methods that directly quantify the stimulus-driven and stimulus-independent components of visual neuron responses in the presence of FEMs. We apply this approach, combined with precise model-based eye tracking, to recordings from primary visual cortex (V1), finding that standard approaches that ignore FEMs typically miss more than half of the stimulus-driven neural response variance, creating substantial biases in measures of response reliability. We show that these effects are likely not isolated to the particular experimental conditions used here, such as the choice of visual stimulus or spike measurement time window, and thus will be a more general problem for V1 recordings in awake primates. We also demonstrate that measurements of the stimulus-driven and stimulus-independent correlations among pairs of V1 neurons can be greatly biased by FEMs. These results thus illustrate the potentially dramatic impact of FEMs on measures of signal and noise in visual neuron activity and also demonstrate a novel approach for controlling for these eye-movement-induced effects. SIGNIFICANCE STATEMENT Distinguishing between the signal and noise in a sensory neuron's activity is typically accomplished by measuring neural responses to repeated presentations of an identical stimulus. For recordings from the visual cortex of awake animals, small “fixational” eye movements (FEMs) inevitably introduce trial-to-trial variability in the visual stimulus, potentially confounding such measures. Here, we show that FEMs often have a dramatic impact on several important measures of response variability for neurons in primary visual cortex. We also present an analytical approach for quantifying signal and noise in visual neuron activity in the presence of FEMs. These results thus highlight the importance of controlling for FEMs in studies of visual neuron function, and demonstrate novel methods for doing so. PMID:27277801

Responses of neurons in cat primary auditory cortex to bird chirps: effects of temporal and spectral context.

PubMed

Bar-Yosef, Omer; Rotman, Yaron; Nelken, Israel

2002-10-01

The responses of neurons to natural sounds and simplified natural sounds were recorded in the primary auditory cortex (AI) of halothane-anesthetized cats. Bird chirps were used as the base natural stimuli. They were first presented within the original acoustic context (at least 250 msec of sounds before and after each chirp). The first simplification step consisted of extracting a short segment containing just the chirp from the longer segment. For the second step, the chirp was cleaned of its accompanying background noise. Finally, each chirp was replaced by an artificial version that had approximately the same frequency trajectory but with constant amplitude. Neurons had a wide range of different response patterns to these stimuli, and many neurons had late response components in addition, or instead of, their onset responses. In general, every simplification step had a substantial influence on the responses. Neither the extracted chirp nor the clean chirp evoked a similar response to the chirp presented within its acoustic context. The extracted chirp evoked different responses than its clean version. The artificial chirps evoked stronger responses with a shorter latency than the corresponding clean chirp because of envelope differences. These results illustrate the sensitivity of neurons in AI to small perturbations of their acoustic input. In particular, they pose a challenge to models based on linear summation of energy within a spectrotemporal receptive field.

Intermediate quality control tests in the development of a superconducting RF cryomodule for CW operation

NASA Astrophysics Data System (ADS)

Pattalwar, Shrikant; Jones, Thomas; Strachan, John; Bate, Robert; Davies, Phil; McIntosh, Peter

2012-06-01

Through an international cryomodule collaboration, ASTeC at Daresbury Laboratory has taken the primary responsibility in leading the development of an optimised Superconducting RF (SRF) cryomodule, operating in CW mode for energy recovery facilities and other high duty cycle accelerators. For high beam current operation, Higher Order Mode (HOM) absorbers are critical components of the SRF Cryomodule, ensuring excessive heating of the accelerating structures and beam instabilities are effectively managed. This paper describes some of the cold tests conducted on the HOM absorbers and other critical components during the construction phase, to ensure that the quality and reliable cryomodule performance is maintained.

A multi-sensor remote sensing approach for measuring primary production from space

NASA Technical Reports Server (NTRS)

Gautier, Catherine

1989-01-01

It is proposed to develop a multi-sensor remote sensing method for computing marine primary productivity from space, based on the capability to measure the primary ocean variables which regulate photosynthesis. The three variables and the sensors which measure them are: (1) downwelling photosynthetically available irradiance, measured by the VISSR sensor on the GOES satellite, (2) sea-surface temperature from AVHRR on NOAA series satellites, and (3) chlorophyll-like pigment concentration from the Nimbus-7/CZCS sensor. These and other measured variables would be combined within empirical or analytical models to compute primary productivity. With this proposed capability of mapping primary productivity on a regional scale, we could begin realizing a more precise and accurate global assessment of its magnitude and variability. Applications would include supplementation and expansion on the horizontal scale of ship-acquired biological data, which is more accurate and which supplies the vertical components of the field, monitoring oceanic response to increased atmospheric carbon dioxide levels, correlation with observed sedimentation patterns and processes, and fisheries management.

Mismatch Negativity in Recent-Onset and Chronic Schizophrenia: A Current Source Density Analysis

PubMed Central

Fulham, W. Ross; Michie, Patricia T.; Ward, Philip B.; Rasser, Paul E.; Todd, Juanita; Johnston, Patrick J.; Thompson, Paul M.; Schall, Ulrich

2014-01-01

Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia. PMID:24949859

Outcome of prosthesis matched and unmatched patella components in primary and revision total knee replacement.

PubMed

Lewis, Peter L; Gamboa, Ai E; Campbell, David G; Lorimer, Michelle

2017-10-01

Although knee replacements have specifically designed patella prostheses that correspond to the geometry of their femoral components, a patella prosthesis that is unmatched to the femoral component may occasionally be inserted. In revision total knee arthroplasty (TKA), an originally resurfaced patella may be left, but the femoral component revised to one that does not match the patella. Few studies have compared the outcome of matched and unmatched patella components in TKA. This study compared the primary or revision TKA outcome of procedures where patella components matched to their femoral counterparts were inserted, with procedures using patella and femoral components that were unmatched. Data on all primary and revision TKA procedures without a patella component or a matched or an unmatched patella component were obtained from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). Revision surgery was the outcome measure. Cumulative percent revised (CPR) were calculated and Hazard ratios with p values were used to test statistical significance. In primary TKA, there were higher rates of revision where unmatched patella components were used, regardless of implant design. There was no difference in the second revision rates of unmatched versus matched patella component groups. This was evident where delayed resurfacing was carried out, and where the patella prosthesis was left alone but the femoral component was changed. All primary TKA procedures require a patella component corresponding to the femoral component if the patella is resurfaced. Conversely, revision knee arthroplasties are not affected by the use of dissimilar patella and femoral components. Copyright © 2017 Elsevier B.V. All rights reserved.

Case report: anaphylactic reaction to guaifenesin.

PubMed

Ray, Manujendra; Faltay, Bela; Haller, Nairmeen Awad

2009-12-01

Adverse drug reactions lead to a significant number of hospital admissions each year and thus contribute to the overall financial burden of health care. Some of these drug reactions are allergic responses. As the overall predictability of allergic responses to drugs remains low, efforts to improve our understanding of the processes underlying these responses continue as we strive toward the ultimate goal of primary prevention. Allergic reactions range from mild pruritic to severe systemic anaphylactic responses. We report a case of a young healthy man who developed an anaphylactic reaction to an over-the-counter expectorant. A skin test showed that the patient had an immunoglobulin E-mediated allergic response to guaifenesin, one of the components of commonly available cough medications. Our review of published literature showed that this is the first report of a severe allergic response to guaifenesin.

The Effects of Reading Racetrack with Direct Instruction Flashcards and a Token System on Sight Word Acquisition for Two Primary Students with Severe Conduct Disorders

ERIC Educational Resources Information Center

Hopewell, Kim; McLaughlin, T. F.; Derby, K. Mark

2011-01-01

Introduction: The purpose of the study was to evaluate the effectiveness of reading racetracks and direct instruction flashcards with two students with behavior disorders. A token economy with a response cost component was also implemented to increase on-task behavior during data collection. Method: The participants were two eight-year-old males.…

Neurofeedback-Based Enhancement of Single Trial Auditory Evoked Potentials: Feasibility in Healthy Subjects.

PubMed

Rieger, Kathryn; Rarra, Marie-Helene; Moor, Nicolas; Diaz Hernandez, Laura; Baenninger, Anja; Razavi, Nadja; Dierks, Thomas; Hubl, Daniela; Koenig, Thomas

2018-03-01

Previous studies showed a global reduction of the event-related potential component N100 in patients with schizophrenia, a phenomenon that is even more pronounced during auditory verbal hallucinations. This reduction assumingly results from dysfunctional activation of the primary auditory cortex by inner speech, which reduces its responsiveness to external stimuli. With this study, we tested the feasibility of enhancing the responsiveness of the primary auditory cortex to external stimuli with an upregulation of the event-related potential component N100 in healthy control subjects. A total of 15 healthy subjects performed 8 double-sessions of EEG-neurofeedback training over 2 weeks. The results of the used linear mixed effect model showed a significant active learning effect within sessions ( t = 5.99, P < .001) against an unspecific habituation effect that lowered the N100 amplitude over time. Across sessions, a significant increase in the passive condition ( t = 2.42, P = .03), named as carry-over effect, was observed. Given that the carry-over effect is one of the ultimate aims of neurofeedback, it seems reasonable to apply this neurofeedback training protocol to influence the N100 amplitude in patients with schizophrenia. This intervention could provide an alternative treatment option for auditory verbal hallucinations in these patients.

Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib vaccine in Canadian Aboriginal and non-Aboriginal infants.

PubMed

Scheifele, David W; Ferguson, Murdo; Predy, Gerald; Dawar, Meena; Assudani, Deepak; Kuriyakose, Sherine; Van Der Meeren, Olivier; Han, Htay-Htay

2015-04-15

This study compared immune responses of healthy Aboriginal and non-Aboriginal infants to Haemophilus influenzae type b (Hib) and hepatitis B virus (HBV) components of a DTaP-HBV-IPV/Hib combination vaccine, 1 month after completing dosing at 2, 4 and 6 months of age. Of 112 infants enrolled in each group, 94 Aboriginal and 107 non-Aboriginal infants qualified for the immunogenicity analysis. Anti-PRP concentrations exceeded the protective minimum (≥0.15 μg/ml) in ≥97% of infants in both groups but geometric mean concentrations (GMCs) were higher in Aboriginal infants (6.12 μg/ml versus 3.51 μg/ml). All subjects were seroprotected (anti-HBs ≥10 mIU/mL) against HBV, with groups having similar GMCs (1797.9 versus 1544.4 mIU/mL, Aboriginal versus non-Aboriginal, respectively). No safety concerns were identified. We conclude that 3-dose primary vaccination with DTaP-HBV-IPV/Hib combination vaccine elicited immune responses to Hib and HBV components that were at least as high in Aboriginal as in non-Aboriginal Canadian infants. Clinical Trial Registration NCT00753649. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

NASA-DoD Lead-Free Electronics Project

NASA Technical Reports Server (NTRS)

Kessel, Kurt R.

2009-01-01

In response to concerns about risks from lead-free induced faults to high reliability products, NASA has initiated a multi-year project to provide manufacturers and users with data to clarify the risks of lead-free materials in their products. The project will also be of interest to component manufacturers supplying to high reliability markets. The project was launched in November 2006. The primary technical objective of the project is to undertake comprehensive testing to generate information on failure modes/criteria to better understand the reliability of: - Packages (e.g., TSOP, BOA, PDIP) assembled and reworked with solder interconnects consisting of lead-free alloys - Packages (e.g., TSOP, BOA, PDIP) assembled and reworked with solder interconnects consisting of mixed alloys, lead component finish/lead-free solder and lead-free component finish/SnPb solder.

NASA-DoD Lead-Free Electronics Project

NASA Technical Reports Server (NTRS)

Kessel, Kurt R.

2009-01-01

In response to concerns about risks from lead-free induced faults to high reliability products, NASA has initiated a multi-year project to provide manufacturers and users with data to clarify the risks of lead-free materials in their products. The project will also be of interest to component manufacturers supplying to high reliability markets. The project was launched in November 2006. The primary technical objective of the project is to undertake comprehensive testing to generate information on failure modes/criteria to better understand the reliability of: - Packages (e.g., TSOP, BGA, PDIP) assembled and reworked with solder interconnects consisting of lead-free alloys - Packages (e.g., TSOP, BGA, PDIP) assembled and reworked with solder interconnects consisting of mixed alloys, lead component finish/lead-free solder and lead-free component finish/SnPb solder.

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

PubMed

Hay, Colin W; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J; MacKenzie, Alasdair

2014-09-01

Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones

PubMed Central

Hay, Colin W.; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J.; MacKenzie, Alasdair

2014-01-01

Summary Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. PMID:25001955

Comprehensive Review of the Future Role of the Reserve Component. Volume 1. Executive Summary and Main Report

DTIC Science & Technology

2011-04-05

C t r Source Integrated Security Posture Defense Planning Scenario April 2008 28 Using selected DoD planning scenarios8 that cover the...Military Sourcing for DoD Humanitarian Crisis Response D C R Mil t r S r i 1. AC primary source for DoD response 2. Some pre-planned RC required...immediately 3. Most RC follow on CRISIS + 30 DAYS Days N o ti o n a l P e rc e n t o f T o ta l F o rc e President Invokes PRC

Feasibility of a physical activity pathway for Irish primary care physiotherapy services.

PubMed

Barrett, Emer M; Hussey, Juliette; Darker, Catherine D

2017-03-01

To establish consensus on a physical activity pathway suitable for use by physiotherapists in Irish primary care. The physical activity pathway "Let's Get Moving" was examined to agree recruitment criteria and seek consensus on component parts. Modified Delphi approach which attempts to achieve a convergence of opinion, over a series of iterations. Three rounds of questionnaires were used. Primary care. 41 senior physiotherapists working in primary care for a median of 6 years (IQR 3.7 to 8.5). Statements achieving consensus; defined as at least 70% of participants scoring a 6 or a 7, indicating high agreement, on a 7 point Likert scale. The response rate was 98%. There was a high degree of consensus for many components of the pathway. Participants agreed that all patients attending physiotherapy should be eligible for recruitment onto the pathway as well as accepting referrals from other health professionals and direct access from the public. Private physiotherapists highlighted concerns about recruiting fee paying patients onto the pathway. The pathway should be integrated into other preventative and chronic disease programmes in primary care. Modifications to the original pathway included the use of a pedometer in addition to the General Practice Physical Activity Questionnaire. Training needs in physical activity screening and motivational interviewing, as well as additional staffing were identified to support implementation. The Physical Activity Pathway "Let's Get Moving" was accepted as a clinically feasible resource to primary care physiotherapists with some modifications and with the support of additional resources. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Attitude control compensator for flexible spacecraft

NASA Technical Reports Server (NTRS)

Goodzeit, Neil E. (Inventor); Linder, David M. (Inventor)

1991-01-01

An attitude control loop for a spacecraft uses a proportional-integral-derivative (PID) controller for control about an axis. The spacecraft body has at least a primary mechanical resonance. The attitude sensors are collocated, or both on the rigid portion of the spacecraft. The flexure attributable to the resonance may result in instability of the system. A compensator for the control loop has an amplitude response which includes a component which rolls off beginning at frequencies below the resonance, and which also includes a component having a notch at a notch frequency somewhat below the resonant frequency. The phase response of the compensator tends toward zero at low frequencies, and tends toward -180.degree. as frequency increases toward the notch frequency. At frequencies above the notch frequency, the phase decreases from +180.degree., becoming more negative, and tending toward -90.degree. at frequencies far above the resonance frequency. Near the resonance frequency, the compensator phase is near zero.

Uplifting Fear Appeals: Considering the Role of Hope in Fear-Based Persuasive Messages.

PubMed

Nabi, Robin L; Myrick, Jessica Gall

2018-01-09

Fear appeal research has focused, understandably, on fear as the primary emotion motivating attitude and behavior change. However, while the threat component of fear appeals associates with fear responses, a fear appeals' efficacy component likely associates with a different emotional experience: hope. Drawing from appraisal theories of emotion in particular, this article theorizes about the role of hope in fear appeals, testing hypotheses with two existing data sets collected within the context of sun safety messages. In both studies, significant interactions between hope and self-efficacy emerged to predict behavioral intentions. Notable main effects for hope also emerged, though with less consistency. Further, these effects persisted despite controlling for the four cognitions typically considered central to fear appeal effectiveness. These results, consistent across two samples, support the claim that feelings of hope in response to fear appeals contribute to their persuasive success. Implications for developing a recursive model of fear appeal processing are discussed.

The response of ecosystem carbon fluxes to LAI and environmental drivers in a maize crop grown in two contrasting seasons.

PubMed

Vitale, Luca; Di Tommasi, Paul; D'Urso, Guido; Magliulo, Vincenzo

2016-03-01

The eddy correlation technique was used to investigate the influence of biophysical variables and crop phenological phases on the behaviour of ecosystem carbon fluxes of a maize crop, in two contrasting growing seasons. In 2009, the reduced water supply during the early growing stage limited leaf area expansion, thus negatively affecting canopy photosynthesis. The variability of gross primary production (GPP) and ecosystem respiration (R eco) was mainly explained by seasonal variation of leaf area index (LAI). The seasonal variation of R eco was positively influenced by soil temperatures (T soil) in 2008 but not in 2009. In 2008, a contribution of both autotrophic and heterotrophic components to total R eco could be hypothesized, while during 2009, autotrophic respiration is supposed to be the most important component. Crop phenological phases affected the response of ecosystem fluxes to biophysical drivers.

Neural Representation of Scale Illusion: Magnetoencephalographic Study on the Auditory Illusion Induced by Distinctive Tone Sequences in the Two Ears

PubMed Central

Kuriki, Shinya; Yokosawa, Koichi; Takahashi, Makoto

2013-01-01

The auditory illusory perception “scale illusion” occurs when a tone of ascending scale is presented in one ear, a tone of descending scale is presented simultaneously in the other ear, and vice versa. Most listeners hear illusory percepts of smooth pitch contours of the higher half of the scale in the right ear and the lower half in the left ear. Little is known about neural processes underlying the scale illusion. In this magnetoencephalographic study, we recorded steady-state responses to amplitude-modulated short tones having illusion-inducing pitch sequences, where the sound level of the modulated tones was manipulated to decrease monotonically with increase in pitch. The steady-state responses were decomposed into right- and left-sound components by means of separate modulation frequencies. It was found that the time course of the magnitude of response components of illusion-perceiving listeners was significantly correlated with smooth pitch contour of illusory percepts and that the time course of response components of stimulus-perceiving listeners was significantly correlated with discontinuous pitch contour of stimulus percepts in addition to the contour of illusory percepts. The results suggest that the percept of illusory pitch sequence was represented in the neural activity in or near the primary auditory cortex, i.e., the site of generation of auditory steady-state response, and that perception of scale illusion is maintained by automatic low-level processing. PMID:24086676

Integrity of the Linker of Nucleoskeleton and Cytoskeleton Is Required for Efficient Herpesvirus Nuclear Egress.

PubMed

Klupp, Barbara G; Hellberg, Teresa; Granzow, Harald; Franzke, Kati; Dominguez Gonzalez, Beatriz; Goodchild, Rose E; Mettenleiter, Thomas C

2017-10-01

Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. IMPORTANCE While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here that dominant negative SUN2 interferes with efficient herpesvirus nuclear egress, apparently by interfering with fusion between the primary virion envelope and outer nuclear membrane. This identifies a new cellular component important for viral egress and implicates LINC complex integrity in nonconventional nuclear membrane trafficking. Copyright © 2017 American Society for Microbiology.

How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex

PubMed Central

Cooke, Sam F.; Bear, Mark F.

2014-01-01

Donald Hebb chose visual learning in primary visual cortex (V1) of the rodent to exemplify his theories of how the brain stores information through long-lasting homosynaptic plasticity. Here, we revisit V1 to consider roles for bidirectional ‘Hebbian’ plasticity in the modification of vision through experience. First, we discuss the consequences of monocular deprivation (MD) in the mouse, which have been studied by many laboratories over many years, and the evidence that synaptic depression of excitatory input from the thalamus is a primary contributor to the loss of visual cortical responsiveness to stimuli viewed through the deprived eye. Second, we describe a less studied, but no less interesting form of plasticity in the visual cortex known as stimulus-selective response potentiation (SRP). SRP results in increases in the response of V1 to a visual stimulus through repeated viewing and bears all the hallmarks of perceptual learning. We describe evidence implicating an important role for potentiation of thalamo-cortical synapses in SRP. In addition, we present new data indicating that there are some features of this form of plasticity that cannot be fully accounted for by such feed-forward Hebbian plasticity, suggesting contributions from intra-cortical circuit components. PMID:24298166

Multivariate objective response detectors (MORD): statistical tools for multichannel EEG analysis during rhythmic stimulation.

PubMed

Felix, Leonardo Bonato; Miranda de Sá, Antonio Mauricio Ferreira Leite; Infantosi, Antonio Fernando Catelli; Yehia, Hani Camille

2007-03-01

The presence of cerebral evoked responses can be tested by using objective response detectors. They are statistical tests that provide a threshold above which responses can be assumed to have occurred. The detection power depends on the signal-to-noise ratio (SNR) of the response and the amount of data available. However, the correlation within the background noise could also affect the power of such detectors. For a fixed SNR, the detection can only be improved at the expense of using a longer stretch of signal. This can constitute a limitation, for instance, in monitored surgeries. Alternatively, multivariate objective response detection (MORD) could be used. This work applies two MORD techniques (multiple coherence and multiple component synchrony measure) to EEG data collected during intermittent photic stimulation. They were evaluated throughout Monte Carlo simulations, which also allowed verifying that correlation in the background reduces the detection rate. Considering the N EEG derivations as close as possible to the primary visual cortex, if N = 4, 6 or 8, multiple coherence leads to a statistically significant higher detection rate in comparison with multiple component synchrony measure. With the former, the best performance was obtained with six signals (O1, O2, T5, T6, P3 and P4).

Joint variability of global runoff and global sea surface temperatures

USGS Publications Warehouse

McCabe, G.J.; Wolock, D.M.

2008-01-01

Global land surface runoff and sea surface temperatures (SST) are analyzed to identify the primary modes of variability of these hydroclimatic data for the period 1905-2002. A monthly water-balance model first is used with global monthly temperature and precipitation data to compute time series of annual gridded runoff for the analysis period. The annual runoff time series data are combined with gridded annual sea surface temperature data, and the combined dataset is subjected to a principal components analysis (PCA) to identify the primary modes of variability. The first three components from the PCA explain 29% of the total variability in the combined runoff/SST dataset. The first component explains 15% of the total variance and primarily represents long-term trends in the data. The long-term trends in SSTs are evident as warming in all of the oceans. The associated long-term trends in runoff suggest increasing flows for parts of North America, South America, Eurasia, and Australia; decreasing runoff is most notable in western Africa. The second principal component explains 9% of the total variance and reflects variability of the El Ni??o-Southern Oscillation (ENSO) and its associated influence on global annual runoff patterns. The third component explains 5% of the total variance and indicates a response of global annual runoff to variability in North Aflantic SSTs. The association between runoff and North Atlantic SSTs may explain an apparent steplike change in runoff that occurred around 1970 for a number of continental regions.

CD4(+) T-cell help amplifies innate signals for primary CD8(+) T-cell immunity.

PubMed

Bedoui, Sammy; Heath, William R; Mueller, Scott N

2016-07-01

CD8(+) T cells provide an important component of protection against intracellular infections and cancer. Immune responses by these T cells involve a primary phase of effector expansion and differentiation, followed by a contraction phase leading to memory formation and, if antigen is re-encountered, a secondary expansion phase with more rapid differentiation. Both primary and secondary phases of CD8(+) T-cell immunity have been shown to depend on CD4(+) T-cell help, although during certain infections the primary phase is variable in this requirement. One explanation for such variability relates to the strength of associated inflammatory signals, with weak signals requiring help. Here, we focus on our studies that have dissected the requirements for help in the primary phase of the CTL response to herpes simplex virus, elucidating intricate interactions and communications between CD4(+) T cells, various dendritic cell subsets, and CD8(+) T cells. We place our studies in the context of others and describe a simple model of help where CD40 signaling amplifies innate signals to enable efficient CD8(+) T-cell expansion and differentiation. This model facilitates CTL induction to various different agents, without altering the qualitative innate signals that direct other important arms of immunity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Automatic quadrature control and measuring system. [using optical coupling circuitry

NASA Technical Reports Server (NTRS)

Hamlet, J. F. (Inventor)

1974-01-01

A quadrature component cancellation and measuring system comprising a detection system for detecting the quadrature component from a primary signal, including reference circuitry to define the phase of the quadrature component for detection is described. A Raysistor optical coupling control device connects an output from the detection system to a circuit driven by a signal based upon the primary signal. Combining circuitry connects the primary signal and the circuit controlled by the Raysistor device to subtract quadrature components. A known current through the optically sensitive element produces a signal defining the magnitude of the quadrature component.

Ipsilateral breast metastasis from a pulmonary adenocarcinoma: a case report and a focused review of the literature

PubMed Central

Shen, Yan-Wei; Sui, Yan-Xia; Zhang, Xiao-Man; Lv, Meng; Zhang, Xiao; Liu, Pei-Jun; Yang, Jin

2015-01-01

Metastases to the breast from extramammary malignancies are extremely rare. Ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis. We report a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 52 year-old female patient presented with mammary gland tingling and dyspnea accompanied with fatigued of 4 months duration and a nodular shadows in the front of the upper lobe was found on a chest computed tomography (CT) scan. The original clinical diagnosis was right breast cancer with lung and bone metastasis, or breast and lung double primary cancers. In addition,on physical examination a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent thoracocentesis and breast biopsy. By imageology, cytology, histology and immunohistochemistry, we diagnosed primary lung cancer with metastases to the right breast and bone. The metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient was administered 4 cycles of cisplatin and docetaxel, although no clinical response was seen, the patient is still alive 9 months after diagnosis. The result of immunohistochemistry is a useful supplement in differential diagnosis. PMID:26464732

Neoadjuvant radiation in primary extremity liposarcoma: correlation of MRI features with histopathology.

PubMed

Wortman, Jeremy R; Tirumani, Sree Harsha; Tirumani, Harika; Shinagare, Atul B; Jagannathan, Jyothi P; Hornick, Jason L; Ramaiya, Nikhil H

2016-05-01

To evaluate MRI features of response of primary extremity liposarcoma (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation. In this IRB-approved study including 125 patients with extremity LPS treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18 patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by two radiologists by consensus. Histopathology of the surgical specimens was reviewed by a pathologist with expertise in sarcomas. In the pleomorphic LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component; and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis. In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in enhancing component, and 5/13 increased in internal fat following RT. Histopathology showed ≥50% residual tumour in 1/5 pleomorphic LPS and 2/13 myxoid LPS. Hyalinization/necrosis of ≥75% was noted in 4/5 pleomorphic LPS and 11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13 myxoid LPS. While pleomorphic LPS showed an increase in size, peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an increase in internal fat. • Pleomorphic LPS commonly increase in size and necrosis on MRI following RT. • Myxoid LPS commonly decrease in size and enhancement on MRI following RT. • Myxoid LPS often increase in fatty component on MRI following RT.

Journal Clubs in Sports Medicine Fellowship Programs: Results From a National Survey and Recommendations for Quality Improvement.

PubMed

Asif, Irfan M; Wiederman, Michael; Kapur, Rahul

2017-11-01

Journal club is a pervasive component of graduate medical education, yet there is no gold standard as to format and logistics. Survey of primary care sports medicine fellowship directors in the United States. Sixty-nine program directors completed the online questionnaire (40% response rate). There were some common aspects to journal club exhibited by a majority of programs, including the general format, required attendance by fellows and expected or required attendance by faculty, the expectation that participants had at least read the article before the meeting, and that meetings occurred during the workday in the work setting without provision of food. There was considerable variation on other aspects, including the objectives of journal club, who had primary responsibility for organizing the session, the criteria for selection of articles, who was invited to attend, and the perceived problems with journal club. This is the first survey investigating the current state of journal club in primary care sports medicine fellowship programs. Several opportunities for educational enhancements exist within journal clubs in primary care sports medicine, including the use of structured tools to guide discussion, providing mechanisms to evaluate the journal club experience as a whole, inviting multidisciplinary team members (eg, statisticians) to discussions, and ensuring that objectives are explicitly stated to participants.

Two Stellar Components in the Halo of the Milky Way

DTIC Science & Technology

2007-12-13

that might be considered, multiple lines of evidence derived from these data clearly confirm that the halo can be resolved into (at least) two primary...of the inner-halo population. Evidence for the dichotomy of the halo The spectroscopy, photometry and astrometry for our large sample of stars were...0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing

Pupil size directly modulates the feedforward response in human primary visual cortex independently of attention.

PubMed

Bombeke, Klaas; Duthoo, Wout; Mueller, Sven C; Hopf, Jens-Max; Boehler, C Nico

2016-02-15

Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing. Copyright © 2015 Elsevier Inc. All rights reserved.

National Partnership for Maternal Safety: Consensus Bundle on Safe Reduction of Primary Cesarean Births-Supporting Intended Vaginal Births.

PubMed

Lagrew, David C; Low, Lisa Kane; Brennan, Rita; Corry, Maureen P; Edmonds, Joyce K; Gilpin, Brian G; Frost, Jennifer; Pinger, Whitney; Reisner, Dale P; Jaffer, Sara

2018-03-01

Cesarean births and associated morbidity and mortality have reached near epidemic proportions. The National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care responded by developing a patient safety bundle to reduce the number of primary cesarean births. Safety bundles outline critical practices to implement in every maternity unit. This National Partnership for Maternity Safety bundle, as with other bundles, is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Bundle components may be adapted to individual facilities, but standardization within an institution is advised. Evidence-based resources and recommendations are provided to assist implementation.

Differentiation of Inflammation-Responsive Astrocytes from Glial Progenitors Generated from Human Induced Pluripotent Stem Cells.

PubMed

Santos, Renata; Vadodaria, Krishna C; Jaeger, Baptiste N; Mei, Arianna; Lefcochilos-Fogelquist, Sabrina; Mendes, Ana P D; Erikson, Galina; Shokhirev, Maxim; Randolph-Moore, Lynne; Fredlender, Callie; Dave, Sonia; Oefner, Ruth; Fitzpatrick, Conor; Pena, Monique; Barron, Jerika J; Ku, Manching; Denli, Ahmet M; Kerman, Bilal E; Charnay, Patrick; Kelsoe, John R; Marchetto, Maria C; Gage, Fred H

2017-06-06

Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1β or tumor necrosis factor α elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1β. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

To the Planets, Comets, and Beyond: A Vision of Sustained Collaboration

NASA Astrophysics Data System (ADS)

Gaboardi, M.; Grauer, M.; Humayun, M.; Dixon, P.

2007-12-01

Our NASA-funded, E/PO partnership, the Student-Teacher Astronomy Resource (STAR) Program, has been successful in integrating current space science knowledge, scientific inquiry, and educational practices. With our focus on the recent NASA Stardust Mission, we engage teachers, students, and the general public in timely, research-based inquiry into space science. One such component of our program is "The Solar System: To the Planets, Comets, and Beyond," a new curricula that is accessible to, and comfortable for, primary educators, many of whom were previously uncomfortable teaching space science. This achievement is the result of ongoing collaboration between a formal primary educator (Grauer), the director of educational outreach for the National High Magnetic Field Laboratory (Dixon), a cosmochemist (Humayun) and a graduate student (Gaboardi), both researchers in the geochemistry program within the NHMFL. Indicators of success in our outreach program include the following: 1- Increased public awareness of research as evidenced by local television, newspaper, and radio coverage, 2- Requests from individual teachers, schools, and school districts for workshops specific to our program, 3- Overwhelmingly positive formal and informal responses from teachers, students, and parents participating in our program, 4- Requests from high-school students for advice involving science fair projects, 5- High level of performance of Grauer's primary students in space science curricula developed as a result of collaboration, and 6- Integration of a space science component into the sustained outreach program provided by the NHMFL. We are currently collecting formal questionnaires from teachers who have participated in our 2007 workshops to explore the following further indicators of success: 1- teachers' use of our curricula, 2- teachers' comfort levels in teaching space science both before and after attending our workshop, and 3- teachers' evaluation of their own space science content knowledge before and after attending our workshop. Based on formal responses from the 2006 cohort, and informal responses from the 2007 cohort, we expect evaluations to be strongly positive.

Transient vibration analytical modeling and suppressing for vibration absorber system under impulse excitation

NASA Astrophysics Data System (ADS)

Wang, Xi; Yang, Bintang; Yu, Hu; Gao, Yulong

2017-04-01

The impulse excitation of mechanism causes transient vibration. In order to achieve adaptive transient vibration control, a method which can exactly model the response need to be proposed. This paper presents an analytical model to obtain the response of the primary system attached with dynamic vibration absorber (DVA) under impulse excitation. The impulse excitation which can be divided into single-impulse excitation and multi-impulse excitation is simplified as sinusoidal wave to establish the analytical model. To decouple the differential governing equations, a transform matrix is applied to convert the response from the physical coordinate to model coordinate. Therefore, the analytical response in the physical coordinate can be obtained by inverse transformation. The numerical Runge-Kutta method and experimental tests have demonstrated the effectiveness of the analytical model proposed. The wavelet of the response indicates that the transient vibration consists of components with multiple frequencies, and it shows that the modeling results coincide with the experiments. The optimizing simulations based on genetic algorithm and experimental tests demonstrate that the transient vibration of the primary system can be decreased by changing the stiffness of the DVA. The results presented in this paper are the foundations for us to develop the adaptive transient vibration absorber in the future.

Model-based analysis of pattern motion processing in mouse primary visual cortex

PubMed Central

Muir, Dylan R.; Roth, Morgane M.; Helmchen, Fritjof; Kampa, Björn M.

2015-01-01

Neurons in sensory areas of neocortex exhibit responses tuned to specific features of the environment. In visual cortex, information about features such as edges or textures with particular orientations must be integrated to recognize a visual scene or object. Connectivity studies in rodent cortex have revealed that neurons make specific connections within sub-networks sharing common input tuning. In principle, this sub-network architecture enables local cortical circuits to integrate sensory information. However, whether feature integration indeed occurs locally in rodent primary sensory areas has not been examined directly. We studied local integration of sensory features in primary visual cortex (V1) of the mouse by presenting drifting grating and plaid stimuli, while recording the activity of neuronal populations with two-photon calcium imaging. Using a Bayesian model-based analysis framework, we classified single-cell responses as being selective for either individual grating components or for moving plaid patterns. Rather than relying on trial-averaged responses, our model-based framework takes into account single-trial responses and can easily be extended to consider any number of arbitrary predictive models. Our analysis method was able to successfully classify significantly more responses than traditional partial correlation (PC) analysis, and provides a rigorous statistical framework to rank any number of models and reject poorly performing models. We also found a large proportion of cells that respond strongly to only one stimulus class. In addition, a quarter of selectively responding neurons had more complex responses that could not be explained by any simple integration model. Our results show that a broad range of pattern integration processes already take place at the level of V1. This diversity of integration is consistent with processing of visual inputs by local sub-networks within V1 that are tuned to combinations of sensory features. PMID:26300738

Abiotic and Biotic Stressors Causing Equivalent Mortality Induce Highly Variable Transcriptional Responses in the Soybean Aphid

PubMed Central

Enders, Laramy S.; Bickel, Ryan D.; Brisson, Jennifer A.; Heng-Moss, Tiffany M.; Siegfried, Blair D.; Zera, Anthony J.; Miller, Nicholas J.

2014-01-01

Environmental stress affects basic organismal functioning and can cause physiological, developmental, and reproductive impairment. However, in many nonmodel organisms, the core molecular stress response remains poorly characterized and the extent to which stress-induced transcriptional changes differ across qualitatively different stress types is largely unexplored. The current study examines the molecular stress response of the soybean aphid (Aphis glycines) using RNA sequencing and compares transcriptional responses to multiple stressors (heat, starvation, and plant defenses) at a standardized stress level (27% adult mortality). Stress-induced transcriptional changes showed remarkable variation, with starvation, heat, and plant defensive stress altering the expression of 3985, 510, and 12 genes, respectively. Molecular responses showed little overlap across all three stressors. However, a common transcriptional stress response was identified under heat and starvation, involved with up-regulation of glycogen biosynthesis and molecular chaperones and down-regulation of bacterial endosymbiont cellular and insect cuticular components. Stressor-specific responses indicated heat affected expression of heat shock proteins and cuticular components, whereas starvation altered a diverse set of genes involved in primary metabolism, oxidative reductive processes, nucleosome and histone assembly, and the regulation of DNA repair and replication. Exposure to host plant defenses elicited the weakest response, of which half of the genes were of unknown function. This study highlights the need for standardizing stress levels when comparing across stress types and provides a basis for understanding the role of general vs. stressor specific molecular responses in aphids. PMID:25538100

Genetic Analysis of Ca 2+ Priming in Arabidopsis Guard Cell Stomatal Closure in Response to the Drought Hormone Abscisic Acid

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

Stephan, Aaron B.

2014-11-01

A primary objective of modern agriculture and biofuel production is to utilize arable land to its fullest potential. However, sub-optimal growing conditions—arising from abiotic stresses such as drought, soil salinity, low humidity, cold, and heat—reduce crop yield and quality. Optimal yield under both stressed and non-stressed conditions requires the plant to activate coping mechanisms at a level commensurate with the severity of the drought stress. The osmotic sensors and associated regulatory mechanisms that initiate drought- and salt-tolerance responses in plants are largely unknown. This research aimed to identify and characterize these initial sensory components.

Compression strength of composite primary structural components

NASA Technical Reports Server (NTRS)

Johnson, Eric R.

1992-01-01

A status report of work performed during the period May 1, 1992 to October 31, 1992 is presented. Research was conducted in three areas: delamination initiation in postbuckled dropped-ply laminates; stiffener crippling initiated by delamination; and pressure pillowing of an orthogonally stiffened cylindrical shell. The geometrically nonlinear response and delamination initiation of compression-loaded dropped-ply laminates is analyzed. A computational model of the stiffener specimens that includes the capability to predict the interlaminar response at the flange free edge in postbuckling is developed. The distribution of the interacting loads between the stiffeners and the shell wall, particularly at the load transfer at the stiffener crossing point, is determined.

Commissioning specialist diabetes services for adults with diabetes: summary of a Diabetes UK Task and Finish group report.

PubMed

Goenka, N; Turner, B; Vora, J

2011-12-01

The increasing prevalence of diabetes, the drive to develop community services for diabetes and the Quality and Outcomes Framework for diabetes have led to improvements in the management of diabetes in primary care settings, with services traditionally provided only in specialist care now provided for many patients with diabetes by non-specialists. Consequently, there is a need to redefine roles, responsibilities and components of a specialist diabetes service to provide for the needs of patients in the National Health Service (NHS) today. The delivery of diabetes care is complex and touches on almost every aspect of the health service. It is the responsibility of those working within commissioning and specialist provider roles to work together with people with diabetes to develop, organize and deliver a full range of integrated diabetes care services. The local delivery model agreed within the local diabetes network, comprising specialist teams, primary care teams, commissioners and people with diabetes, should determine how the diabetes specialist services are organizsed. It should identify the roles and responsibilities of provider organizations to ensure that the right person provides the right care, at the right time, and in the right place. We summarize a report entitled 'Commissioning Diabetes Specialist Services for Adults with Diabetes', which has been produced, as a 'Task and Finish' group activity within Diabetes UK, to assist managers, commissioners and healthcare professionals to provide advice on the structure, roles and components of specialist diabetes services for adults. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Primary Care Clinic Re-Design for Prescription Opioid Management.

PubMed

Parchman, Michael L; Von Korff, Michael; Baldwin, Laura-Mae; Stephens, Mark; Ike, Brooke; Cromp, DeAnn; Hsu, Clarissa; Wagner, Ed H

The challenge of responding to prescription opioid overuse within the United States has fallen disproportionately on the primary care clinic setting. Here we describe a framework comprised of 6 Building Blocks to guide efforts within this setting to address the use of opioids for chronic pain. Investigators conducted site visits to thirty primary care clinics across the United States selected for their use of team-based workforce innovations. Site visits included interviews with leadership, clinic tours, observations of clinic processes and team meetings, and interviews with staff and clinicians. Data were reviewed to identify common attributes of clinic system changes around chronic opioid therapy (COT) management. These concepts were reviewed to develop narrative descriptions of key components of changes made to improve COT use. Twenty of the thirty sites had addressed improvements in COT prescribing. Across these sites a common set of 6 Building Blocks were identified: 1) providing leadership support; 2) revising and aligning clinic policies, patient agreements (contracts) and workflows; 3) implementing a registry tracking system; 4) conducting planned, patient-centered visits; 5) identifying resources for complex patients; and 6) measuring progress toward achieving clinic objectives. Common components of clinic policies, patient agreements and data tracked in registries to assess progress are described. In response to prescription opioid overuse and the resulting epidemic of overdose and addiction, primary care clinics are making improvements driven by a common set of best practices that address complex challenges of managing COT patients in primary care settings. © Copyright 2017 by the American Board of Family Medicine.

HD 143 418 - An Interacting Binary with a Subsynchronously Rotating Primary

NASA Astrophysics Data System (ADS)

Mikulášek, Z.; Zverko, J.; Žižňovský, J.; Krtička, J.; Iliev, I. Kh.; Kudryavtsev, D. O.; Gráf, T.; Zejda, M.

2010-12-01

HD 143418 is a non-eclipsing double-lined close binary with orbital period Porb=2.282520 d. The photometrically and spectroscopically dominant primary component is a normal A5V star in the middle of its stay on the main sequence with extremely slow, subsynchronous rotation (Prot being about 14 days!). Its photometric monitoring since 1982 revealed orbitally modulated variations with changing form and amplitude. The advanced principal component analysis (APCA) disentangling extract-ed a steady part of light curves obviously caused by the ellipticity of the primary. Seasonal components of the light curves may be related to an expected incidence of circumstellar matter ejected from the tidally spinning up primary component. A possible scenario of the synchronisation process is also briefly discussed.

An Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

DTIC Science & Technology

2008-09-03

shock were biocompatible in vivo, retained potent antibody responses, and were well tolerated by rhesus macaques. Vaccinated primates were completely...results indicate that the vaccines were biocompatible by i.d. administration and physical separation. Seroconversion also occurred after the primary...the vaccinated animals, suggesting that the potency of this vaccine was maintained. Cellular immu- nity , not addressed in our study, may also be

A field guide for rapid assessment of post-wildfire recovery potential in sagebrush and pinon-juniper ecosystems in the Great Basin: Evaluating resilience to disturbance and resistance to invasive annual grasses and predicting vegetation response

Treesearch

Richard F. Miller; Jeanne C. Chambers; Mike Pellant

2015-01-01

This field guide provides a framework for rapidly evaluating post-fire resilience to disturbance, or recovery potential, and resistance to invasive annual grasses, and for determining the need and suitability of the burned area for seeding. The framework identifies six primary components that largely determine resilience to disturbance, resistance to invasive grasses,...

Dissociation of Innate Immune Responses in Microglia Infected with Listeria monocytogenes

PubMed Central

Frande-Cabanes, Elisabet; Fernandez-Prieto, Lorena; Calderon-Gonzalez, Ricardo; Rodríguez-Del Río, Estela; Yañez-Diaz, Sonsoles; López-Fanarraga, Monica; Alvarez-Domínguez, Carmen

2014-01-01

Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. Here, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. Whereas the bacterial gene hly seems responsible for both transcriptional programmes in macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)-regulated transcriptional programme. Listeria also represses in microglia the late immune response gathered in two clusters, microbial degradation, and interferon (IFN)-inducible genes. The bacterial gene actA was required in microglia to induce TNF-regulated responses and to repress the late response. Isolation of microglial phagosomes revealed a phagosomal environment unable to destroy Listeria. Microglial phagosomes were also defective in several signaling and trafficking components reported as relevant for Listeria innate immune responses. This transcriptional strategy in microglia induced high levels of TNF-α and monocyte chemotactic protein-1 and low production of other neurotoxic compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. These cytokines and toxic microglial products are also released by primary microglia, and this cytokine and chemokine cocktail display a low potential to trigger neuronal apoptosis. This overall bacterial strategy strongly suggests that microglia limit Listeria inflammation pattern exclusively through TNF-mediated responses to preserve brain integrity. GLIA 2014;62:233–246 PMID:24311463

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

PubMed

Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C L; Tanaka, Yuetsu; Xia, Zongping

2016-04-01

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains

PubMed Central

Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C. L.; Tanaka, Yuetsu; Xia, Zongping

2016-01-01

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation. PMID:27082114

[Perissodactyla: the primary structure of hemoglobins from the lowland tapir (Tapirus terrestris): glutamic acid in position 2 of the beta chains].

PubMed

Mazur, G; Braunitzer, G

1984-09-01

The hemoglobins from a lowland tapir (Tapirus terrestris) were analysed and the complete primary structure is described. The globin chains were separated on CM cellulose column in 8M urea and the amino-acid sequences were determined in the liquid phase sequenator. The results show that globin consists of two alpha chains (alpha I and alpha II) and beta major and beta minor components. The alpha chains differ only at one position: alpha I contains aspartic acid and alpha II glycine. The beta chains are heterogeneous: aspartic and glutamic acid were found at position beta 21 and beta 73 of the beta major components and asparagine and serine at position beta 139. In the beta minor components four positions were found with more than one amino acid, namely beta 2, beta 4, beta 6 and beta 56. The sequences are compared with those of man, horse and rhinoceros. Four residues of horse methemoglobin, which are involved in the alpha 1 beta 1 contacts are substituted in tapir hemoglobins. In the alpha chains: alpha 107(G14)Ser----Val, alpha 111-(G18) Val----Leu, alpha 115(GH3) Asn----Asp or Gly; in the beta chains: beta 116(G18) Arg----Gln. The amino acid at beta 2 of the major components is glutamic acid while glutamine and histidine are found in the minor components. Although glutamic acid, a binding site for ATP, does not interact with 2,3-bisphosphoglycerate, glutamine and histidine in the minor components are responsible for the slight effect of 2,3-bisphosphoglycerate on tapir hemoglobin.

Spatial summation revealed in the earliest visual evoked component C1 and the effect of attention on its linearity.

PubMed

Chen, Juan; Yu, Qing; Zhu, Ziyun; Peng, Yujia; Fang, Fang

2016-01-01

In natural scenes, multiple objects are usually presented simultaneously. How do specific areas of the brain respond to multiple objects based on their responses to each individual object? Previous functional magnetic resonance imaging (fMRI) studies have shown that the activity induced by a multiobject stimulus in the primary visual cortex (V1) can be predicted by the linear or nonlinear sum of the activities induced by its component objects. However, there has been little evidence from electroencephelogram (EEG) studies so far. Here we explored how V1 responded to multiple objects by comparing the EEG signals evoked by a three-grating stimulus with those evoked by its two components (the central grating and 2 flanking gratings). We focused on the earliest visual component C1 (onset latency of ∼50 ms) because it has been shown to reflect the feedforward responses of neurons in V1. We found that when the stimulus was unattended, the amplitude of the C1 evoked by the three-grating stimulus roughly equaled the sum of the amplitudes of the C1s evoked by its two components, regardless of the distances between these gratings. When the stimulus was attended, this linear spatial summation existed only when the three gratings were far apart from each other. When the three gratings were close to each other, the spatial summation became compressed. These results suggest that the earliest visual responses in V1 follow a linear summation rule when attention is not involved and that attention can affect the earliest interactions between multiple objects. Copyright © 2016 the American Physiological Society.

Potential improvements in horizontal very broadband seismic data in the IRIS/USGS component of the Global Seismic Network

USGS Publications Warehouse

Ringler, Adam; Steim, J.M.; Zandt, T; Hutt, Charles R.; Wilson, David; Storm, Tyler

2016-01-01

The Streckeisen STS‐1 has been the primary vault‐type seismometer used in the over‐150‐station Global Seismographic Network (GSN). This sensor has long been known for its outstanding vertical, very long‐period (e.g., >100  s period), and low‐noise performance, although the horizontal long‐period noise performance is less well known. The STS‐1 is a limited, important resource, because it is no longer made or supported by the original manufacturer. We investigate the incoherent noise of horizontal‐component sensors, where coherent signals among sensors have been removed, giving an upper bound on the self‐noise of both the STS‐1 and STS‐2 horizontal components. Our findings suggest that a well‐installed STS‐2 could potentially produce data with similar or better incoherent noise levels to that of a horizontal‐component STS‐1. Along with our experimental investigation, we compare background noise levels for a calendar year at Incorporated Research Institutions for Seismology/U.S. Geological Survey network stations, which comprise approximately two‐thirds of the GSN, with collocated STS‐1 and STS‐2 seismometers. The use of an STS‐2‐class of sensor (flat to velocity to 120 s period) to acquire low‐frequency data in surface‐vault installations would allow network operators to focus more attention on improving vertical data. In order to deal with the difference in instrument response shapes between the two instruments, we detail two different time‐domain filters that would allow users to convert broadband STS‐2 data into very broadband data with a response similar to that of an STS‐1 (flat to velocity to 360 s period). We conclude that the complexity of the current primary horizontal vault sensors in the GSN may not be necessary until we are better able to isolate surface horizontal sensors from various noise sources.

Monoclonal antibodies for diagnosis and treatment.

PubMed

Dunn, D L

1993-11-01

One of the marvels of the host immune response is its response to antigenic foreign substances by manufacturing proteins that bind tenaciously to their targets. These proteins are antibodies or immunoglobulins produced in vast diversity during an individual's lifetime. By virtue of this process, the mammalian host possesses the innate ability to mount an initial response to antigens to which there has been no prior experience and to develop an even more effective response on reexposure to these same substances. This capacity to distinguish self from nonself is one of the most basic aspects of the cellular and humoral arms of the immune response and is one of the primary means by which the host combats infection caused by many different types of pathogens. In this context, antibodies have long been recognized as a critical component of host defenses and are capable of binding to invading microbes and microbial toxins.

Neuron discharges in the rat auditory cortex during electrical intracortical stimulation.

PubMed

Maldonado, P E; Altman, J A; Gerstein, G L

1998-01-01

Studies were carried out in rats anesthetized with ketamine or nembutal, with recording of multicellular activity (with separate identification of responses from individual neurons) in the primary auditory cortex before and after electrical intracortical microstimulation. These experiments showed that about half of the set of neurons studied produced responses to short tonal bursts, these responses having two components-initial discharges arising in response to the sound, and afterdischarge occurring after pauses of 50-100 msec. Afterdischarges lasted at least several seconds, and were generally characterized by a rhythmic structure (with a frequency of 8-12 Hz). After electrical microstimulation, the level of spike activity increased, especially in afterdischarges, and this increase could last up to 4 h. Combined peristimulus histograms, cross-correlations, and gravitational analyses were used to demonstrate interactions of neurons, which increased after electrical stimulation and were especially pronounced in the response afterdischarges.

In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components

PubMed Central

Belcher, Scott M.; Cookman, Clifford J.; Patisaul, Heather B.; Stapleton, Heather M.

2014-01-01

Firemaster® 550 (FM 550) is a mixture of brominated and triarylphosphate flame retardants used in polyurethane foam-based products. The primary components are also used in numerous other applications and are thus common household and industrial contaminants. Our previous animal studies suggested that FM 550 exposure may alter metabolism and cause weight gain. Employing human nuclear receptor (NR) luciferase reporter assays, the goal of this study was to evaluate the agonist actions of FM 550 and its constituent compounds at NRs with known roles in establishing or regulating energy balance. FM 550 was found to have significant agonist activity only at the master regulator of adipocyte differentiation PPARγ. As a result, the concentration response relationships and relative activities of FM 550 at PPARγ were investigated in more detail with the contribution of each chemical component defined and compared to the activities of the prototypical PPARγ environmental ligands triphenyltin and tributylytin. The resulting data indicated that the primary metabolic disruptive effects of FM 550 were likely mediated by the activity of the triarylphosphates at PPARγ, and have identified TPP as a candidate metabolic disruptor that also acts as a cytotoxicant. PMID:24786373

Human leucocyte antigen class I-redirected anti-tumour CD4+ T cells require a higher T cell receptor binding affinity for optimal activity than CD8+ T cells.

PubMed

Tan, M P; Dolton, G M; Gerry, A B; Brewer, J E; Bennett, A D; Pumphrey, N J; Jakobsen, B K; Sewell, A K

2017-01-01

CD4 + T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4 + T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4 + T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer. The lack of help from the co-receptor CD8 glycoprotein in CD4 + cells might result in these cells requiring a different optimal TCR binding affinity. Here we compared primary CD4 + and CD8 + T cells expressing wild-type and a range of affinity-enhanced TCRs specific for the HLA A*0201-restricted NY-ESO-1- and gp100 tumour antigens. Our major findings are: (i) redirected primary CD4 + T cells expressing TCRs of sufficiently high affinity exhibit a wide range of effector functions, including cytotoxicity, in response to cognate peptide; and (ii) optimal TCR binding affinity is higher in CD4 + T cells than CD8 + T cells. These results indicate that the CD4 + T cell component of current adoptive therapies using TCRs optimized for CD8 + T cells is below par and that there is room for substantial improvement. © 2016 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Primary healthcare reform in the United Nations Relief and Works Agency for Palestine Refugees in the Near East.

PubMed

Santoro, A; Abu-Rmeileh, N; Khader, A; Seita, A; McKee, M

2016-09-25

Palestinian refugees served by the United Nation Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) are experiencing increasing rates of diagnosis of non-communicable diseases. In response, in 2011 UNRWA initiated an Agency-wide programme of primary healthcare reform, informed by the Chronic Care Model framework. Health services were reorganized following a family-centred approach, with delivery by multidisciplinary family health teams supported by updated technical advice. An inclusive clinical information system, termed e-Health, was implemented to collect a wide range of health information, with a focus on continuity of treatment. UNRWA was able to bring about these wide-ranging changes within its existing resources, reallocating finances, reforming its payment mechanisms, and modernizing its drug-procurement policies. While specific components of UNRWA's primary healthcare reform are showing promising results, additional efforts are needed to empower patients further and to strengthen involvement of the community.

Operational and maintenance instruction manual for the Ingham County Geriatric Medical Care Facility solar water-heating system

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

Not Available

The Ingham County solar system consists of approximately 10,000 square feet of solar collectors connected in a closed configuration loop. The primary loop solution is a 1:12 mixture of water and propylene glycol which flows through the tube side of a heat exchanger connected to the primary storage tank. The heat energy which is supplied to the primary storage tank is subsequently used to preheat the temperature of the laundry water, kitchen water, and domestic potable water. Included in this report are: detailed drawings and flow chart; operational methodology; preventive maintenance instructions; general instructions and safety precautions; and a correctivemore » maintenance and tabulation of failure modes. Appendices include: manufacturers technical manual and component specifications; IBM data sensors and responsibilities; digital county monitor operations manual; and on site monitor operations manual. Reference CAPE-2834. (LS)« less

Nonlinear transient survival level seismic finite element analysis of Magellan ground based telescope

NASA Astrophysics Data System (ADS)

Griebel, Matt; Buleri, Christine; Baylor, Andrew; Gunnels, Steve; Hull, Charlie; Palunas, Povilas; Phillips, Mark

2016-07-01

The Magellan Telescopes are a set of twin 6.5 meter ground based optical/near-IR telescopes operated by the Carnegie Institution for Science at the Las Campanas Observatory (LCO) in Chile. The primary mirrors are f/1.25 paraboloids made of borosilicate glass and a honeycomb structure. The secondary mirror provides both f/11 and f/5 focal lengths with two Nasmyth, three auxiliary, and a Cassegrain port on the optical support structure (OSS). The telescopes have been in operation since 2000 and have experienced several small earthquakes with no damage. Measurement of in situ response of the telescopes to seismic events showed significant dynamic amplification, however, the response of the telescopes to a survival level earthquake, including component level forces, displacements, accelerations, and stresses were unknown. The telescopes are supported with hydrostatic bearings that can lift up under high seismic loading, thus causing a nonlinear response. For this reason, the typical response spectrum analysis performed to analyze a survival level seismic earthquake is not sufficient in determining the true response of the structure. Therefore, a nonlinear transient finite element analysis (FEA) of the telescope structure was performed to assess high risk areas and develop acceleration responses for future instrument design. Several configurations were considered combining different installed components and altitude pointing directions. A description of the models, methodology, and results are presented.

Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

PubMed Central

Van Duyne, Rachel; Guendel, Irene; Klase, Zachary; Narayanan, Aarthi; Coley, William; Jaworski, Elizabeth; Roman, Jessica; Popratiloff, Anastas; Mahieux, Renaud; Kehn-Hall, Kylene; Kashanchi, Fatah

2012-01-01

The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus. PMID:22808228

Unique and shared inflammatory profiles of human brain endothelia and pericytes.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Jansson, Deidre; Heppner, Peter A; O'Carroll, Simon J; Mee, Edward W; Faull, Richard L M; Curtis, Maurice; Dragunow, Mike

2018-05-11

Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed. To study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1β, TNFα, LPS, IFN-γ, TGF-β 1 , IL-6, and IL-4). Secretome analysis was performed to identify unique secretions of endothelia and pericytes in response to IL-1β. Endothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1β. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1β, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro. Here, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature.

Correlates of a single cortical action potential in the epidural EEG

PubMed Central

Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

2015-01-01

To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

Basic instinct undressed: early spatiotemporal processing for primary sexual characteristics.

PubMed

Legrand, Lore B; Del Zotto, Marzia; Tyrand, Rémi; Pegna, Alan J

2013-01-01

This study investigates the spatiotemporal dynamics associated with conscious and non-conscious processing of naked and dressed human bodies. To this effect, stimuli of naked men and women with visible primary sexual characteristics, as well as dressed bodies, were presented to 20 heterosexual male and female participants while acquiring high resolution EEG data. The stimuli were either consciously detectable (supraliminal presentations) or were rendered non-conscious through backward masking (subliminal presentations). The N1 event-related potential component was significantly enhanced in participants when they viewed naked compared to dressed bodies under supraliminal viewing conditions. More importantly, naked bodies of the opposite sex produced a significantly greater N1 component compared to dressed bodies during subliminal presentations, when participants were not aware of the stimulus presented. A source localization algorithm computed on the N1 showed that the response for naked bodies in the supraliminal viewing condition was stronger in body processing areas, primary visual areas and additional structures related to emotion processing. By contrast, in the subliminal viewing condition, only visual and body processing areas were found to be activated. These results suggest that naked bodies and primary sexual characteristics are processed early in time (i.e., <200 ms) and activate key brain structures even when they are not consciously detected. It appears that, similarly to what has been reported for emotional faces, sexual features benefit from automatic and rapid processing, most likely due to their high relevance for the individual and their importance for the species in terms of reproductive success.

Finite Element Model Calibration Approach for Area I-X

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Reaves, Mercedes C.; Buehrle, Ralph D.; Templeton, Justin D.; Gaspar, James L.; Lazor, Daniel R.; Parks, Russell A.; Bartolotta, Paul A.

2010-01-01

Ares I-X is a pathfinder vehicle concept under development by NASA to demonstrate a new class of launch vehicles. Although this vehicle is essentially a shell of what the Ares I vehicle will be, efforts are underway to model and calibrate the analytical models before its maiden flight. Work reported in this document will summarize the model calibration approach used including uncertainty quantification of vehicle responses and the use of non-conventional boundary conditions during component testing. Since finite element modeling is the primary modeling tool, the calibration process uses these models, often developed by different groups, to assess model deficiencies and to update parameters to reconcile test with predictions. Data for two major component tests and the flight vehicle are presented along with the calibration results. For calibration, sensitivity analysis is conducted using Analysis of Variance (ANOVA). To reduce the computational burden associated with ANOVA calculations, response surface models are used in lieu of computationally intensive finite element solutions. From the sensitivity studies, parameter importance is assessed as a function of frequency. In addition, the work presents an approach to evaluate the probability that a parameter set exists to reconcile test with analysis. Comparisons of pretest predictions of frequency response uncertainty bounds with measured data, results from the variance-based sensitivity analysis, and results from component test models with calibrated boundary stiffness models are all presented.

Finite Element Model Calibration Approach for Ares I-X

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Reaves, Mercedes C.; Buehrle, Ralph D.; Templeton, Justin D.; Lazor, Daniel R.; Gaspar, James L.; Parks, Russel A.; Bartolotta, Paul A.

2010-01-01

Ares I-X is a pathfinder vehicle concept under development by NASA to demonstrate a new class of launch vehicles. Although this vehicle is essentially a shell of what the Ares I vehicle will be, efforts are underway to model and calibrate the analytical models before its maiden flight. Work reported in this document will summarize the model calibration approach used including uncertainty quantification of vehicle responses and the use of nonconventional boundary conditions during component testing. Since finite element modeling is the primary modeling tool, the calibration process uses these models, often developed by different groups, to assess model deficiencies and to update parameters to reconcile test with predictions. Data for two major component tests and the flight vehicle are presented along with the calibration results. For calibration, sensitivity analysis is conducted using Analysis of Variance (ANOVA). To reduce the computational burden associated with ANOVA calculations, response surface models are used in lieu of computationally intensive finite element solutions. From the sensitivity studies, parameter importance is assessed as a function of frequency. In addition, the work presents an approach to evaluate the probability that a parameter set exists to reconcile test with analysis. Comparisons of pre-test predictions of frequency response uncertainty bounds with measured data, results from the variance-based sensitivity analysis, and results from component test models with calibrated boundary stiffness models are all presented.

NPS alternate techsat satellite, design project for AE-4871

NASA Technical Reports Server (NTRS)

1993-01-01

This project was completed as part of AE-4871, Advanced Spacecraft Design. The intent of the course is to provide experience in the design of all the major components in a spacecraft system. Team members were given responsibility for the design of one of the six primary subsystems: power, structures, propulsion, attitude control, telemetry, tracking and control (TT&C), and thermal control. In addition, a single member worked on configuration control, launch vehicle integration, and a spacecraft test plan. Given an eleven week time constraint, a preliminary design of each subsystem was completed. Where possible, possible component selections were also made. Assistance for this project came principally from the Naval Research Laboratory's Spacecraft Technology Branch. Specific information on components was solicited from representatives in industry. The design project centers on a general purpose satellite bus that is currently being sought by the Strategic Defense Initiative.

NASA-DoD Lead-Free Electronics Project

NASA Technical Reports Server (NTRS)

Kessel, Kurt

2009-01-01

In response to concerns about risks from lead-free induced faults to high reliability products, NASA has initiated a multi-year project to provide manufacturers and users with data to clarify the risks of lead-free materials in their products. The project will also be of interest to component manufacturers supplying to high reliability markets. The project was launched in November 2006. The primary technical objective of the project is to undertake comprehensive testing to generate information on failure modes/criteria to better understand the reliability of: (1) Packages (e.g., Thin Small Outline Package [TSOP], Ball Grid Array [BGA], Plastic Dual In-line Package [PDIP]) assembled and reworked with solder interconnects consisting of lead-free alloys (2) Packages (e.g., TSOP, BGA, PDIP) assembled and reworked with solder interconnects consisting of mixed alloys, lead component finish/lead-free solder and lead-free component finish/SnPb solder

Immunodominance changes as a function of the infecting dengue virus serotype and primary versus secondary infection.

PubMed

Weiskopf, Daniela; Angelo, Michael A; Sidney, John; Peters, Bjoern; Shresta, Sujan; Sette, Alessandro

2014-10-01

Dengue virus (DENV) is the causative agent of dengue fever (DF). This disease can be caused by any of four DENV serotypes (DENV1 to -4) which share 67 to 75% sequence homology with one another. The effect of subsequent infections with different serotypes on the T cell repertoire is not fully understood. We utilized mice transgenic for human leukocyte antigens (HLA) lacking the alpha/beta interferon (IFN-α/β) receptor to study responses to heterologous DENV infection. First, we defined the primary T cell response to DENV3 in the context of a wide range of HLA molecules. The primary DENV3 immune response recognized epitopes derived from all 10 DENV proteins, with a significant fraction of the response specific for structural proteins. This is in contrast to primary DENV2 infection, in which structural proteins are a minor component of the response, suggesting differential antigen immunodominance as a function of the infecting serotype. We next investigated the effect of secondary heterologous DENV infection on the T cell repertoire. In the case of both DENV2/3 and DENV3/2 heterologous infections, recognition of conserved/cross-reactive epitopes was either constant or expanded compared to that in homologous infection. Furthermore, in heterologous infection, previous infection with a different serotype impaired the development of responses directed to serotype-specific but not conserved epitopes. Thus, a detrimental effect of previous heterotypic responses might not be due to dysfunctional and weakly cross-reactive epitopes dominating the response. Rather, responses to the original serotype might limit the magnitude of responses directed against epitopes that are either cross-reactive to or specific for the most recently infecting serotype. DENV transmission occurs in more than 100 countries and is an increasing public health problem in tropical and subtropical regions. At present, no effective antiviral therapy or licensed vaccine exists, and treatment is largely supportive in nature. Disease can be caused by any of the four DENV serotypes (DENV1 to -4), which share a high degree of sequence homology with one another. In this study, we have addressed the question of how the T cell repertoire changes as a function of infections with different serotypes and of subsequent heterologous secondary infections. This is of particular interest in the field of dengue viruses, in which secondary infections with different DENV serotypes increase the risk of severe disease. Our results on the evolution of the immune response after primary and secondary infections provide new insights into HLA-restricted T cell responses against DENV relevant for the design of a vaccine against DENV. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Characterization of an ntrX mutant of Neisseria gonorrhoeae reveals a response regulator that controls expression of respiratory enzymes in oxidase-positive proteobacteria.

PubMed

Atack, John M; Srikhanta, Yogitha N; Djoko, Karrera Y; Welch, Jessica P; Hasri, Norain H M; Steichen, Christopher T; Vanden Hoven, Rachel N; Grimmond, Sean M; Othman, Dk Seti Maimonah Pg; Kappler, Ulrike; Apicella, Michael A; Jennings, Michael P; Edwards, Jennifer L; McEwan, Alastair G

2013-06-01

NtrYX is a sensor-histidine kinase/response regulator two-component system that has had limited characterization in a small number of Alphaproteobacteria. Phylogenetic analysis of the response regulator NtrX showed that this two-component system is extensively distributed across the bacterial domain, and it is present in a variety of Betaproteobacteria, including the human pathogen Neisseria gonorrhoeae. Microarray analysis revealed that the expression of several components of the respiratory chain was reduced in an N. gonorrhoeae ntrX mutant compared to that in the isogenic wild-type (WT) strain 1291. These included the cytochrome c oxidase subunit (ccoP), nitrite reductase (aniA), and nitric oxide reductase (norB). Enzyme activity assays showed decreased cytochrome oxidase and nitrite reductase activities in the ntrX mutant, consistent with microarray data. N. gonorrhoeae ntrX mutants had reduced capacity to survive inside primary cervical cells compared to the wild type, and although they retained the ability to form a biofilm, they exhibited reduced survival within the biofilm compared to wild-type cells, as indicated by LIVE/DEAD staining. Analyses of an ntrX mutant in a representative alphaproteobacterium, Rhodobacter capsulatus, showed that cytochrome oxidase activity was also reduced compared to that in the wild-type strain SB1003. Taken together, these data provide evidence that the NtrYX two-component system may be a key regulator in the expression of respiratory enzymes and, in particular, cytochrome c oxidase, across a wide range of proteobacteria, including a variety of bacterial pathogens.

Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations.

PubMed

Ueberall, Michael A; Mueller-Schwefe, Gerhard H H

2016-01-01

To evaluate the benefit-risk profile (BRP) of oxycodone/naloxone (OXN) and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a neuropathic component (NC) in routine clinical practice. This was a blinded end point analysis of randomly selected 12-week routine/open-label data of the German Pain Registry on adult patients with cLBP-NC who initiated an index treatment in compliance with the current German prescribing information between 1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was defined as a composite of three efficacy components (≥30% improvement of pain, pain-related disability, and quality of life each at the end of observation vs baseline) and three tolerability components (normal bowel function, absence of either central nervous system side effects, and treatment-emergent adverse event [TEAE]-related treatment discontinuation during the observation period) adopted to reflect BRP assessments under real-life conditions. Demographic as well as baseline and pretreatment characteristics were comparable for the randomly selected data sets of both index groups without any indicators for critical selection biases. Treatment with OXN resulted formally in a BRP noninferior to that of TAP and showed a significantly higher primary end point response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; P =0.014), due to superior analgesic effects. Between-group differences increased with stricter response definitions for all three efficacy components in favor of OXN: ≥30%/≥50%/≥70% response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1% vs 83.5%/54.1%/15.8% ( P = ns/0.031/<0.001), for pain-related disability in 78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% ( P =0.043/0.018/0.001), and for quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% ( P =0.026/0.022/0.017). Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72.2%), reported no central nervous system side effects (91.4% vs 89.5%), or completed the 12-week evaluation period without any TEAE-related treatment discontinuations (93.0% vs 92.5%) were similar for both index medications ( P = ns for each comparison). In daily practice, the BRP of OXN proved to be noninferior to that of TAP in patients with cLBP-NC, but showed a superior efficacy if stricter analgesic response definitions were evaluated.

Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations

PubMed Central

Ueberall, Michael A; Mueller-Schwefe, Gerhard H H

2016-01-01

Objective To evaluate the benefit–risk profile (BRP) of oxycodone/naloxone (OXN) and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a neuropathic component (NC) in routine clinical practice. Methods This was a blinded end point analysis of randomly selected 12-week routine/open-label data of the German Pain Registry on adult patients with cLBP-NC who initiated an index treatment in compliance with the current German prescribing information between 1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was defined as a composite of three efficacy components (≥30% improvement of pain, pain-related disability, and quality of life each at the end of observation vs baseline) and three tolerability components (normal bowel function, absence of either central nervous system side effects, and treatment-emergent adverse event [TEAE]-related treatment discontinuation during the observation period) adopted to reflect BRP assessments under real-life conditions. Results Demographic as well as baseline and pretreatment characteristics were comparable for the randomly selected data sets of both index groups without any indicators for critical selection biases. Treatment with OXN resulted formally in a BRP noninferior to that of TAP and showed a significantly higher primary end point response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; P=0.014), due to superior analgesic effects. Between-group differences increased with stricter response definitions for all three efficacy components in favor of OXN: ≥30%/≥50%/≥70% response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1% vs 83.5%/54.1%/15.8% (P= ns/0.031/<0.001), for pain-related disability in 78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% (P=0.043/0.018/0.001), and for quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% (P=0.026/0.022/0.017). Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72.2%), reported no central nervous system side effects (91.4% vs 89.5%), or completed the 12-week evaluation period without any TEAE-related treatment discontinuations (93.0% vs 92.5%) were similar for both index medications (P= ns for each comparison). Conclusion In daily practice, the BRP of OXN proved to be noninferior to that of TAP in patients with cLBP-NC, but showed a superior efficacy if stricter analgesic response definitions were evaluated. PMID:27881925

Multi-scale roughness spectra of Mount St. Helens debris flows

NASA Technical Reports Server (NTRS)

Austin, Richard T.; England, Anthony W.

1993-01-01

A roughness spectrum allows surface structure to be interpreted as a sum of sinusoidal components with differing wavelengths. Knowledge of the roughness spectrum gives insight into the mechanisms responsible for electromagnetic scattering at a given wavelength. Measured spectra from 10-year-old primary debris flow surfaces at Mount St. Helens conform to a power-law spectral model, suggesting that these surfaces are scaling over the measured range of spatial frequencies. Measured spectra from water-deposited surfaces deviate from this model.

Terrestrial biogeochemical cycles - Global interactions with the atmosphere and hydrology

NASA Technical Reports Server (NTRS)

Schimel, David S.; Parton, William J.; Kittel, Timothy G. F.

1991-01-01

A review is presented of developments in ecosystem theory, remote sensing, and geographic information systems that support new endeavors in spatial modeling. A paradigm has emerged to predict ecosystem behavior based on understanding responses to multiple resources. Ecosystem models couple primary production to decomposition and nutrient availability utilizing this paradigm. It is indicated that coupling of transport and ecosystem processes alters the behavior of earth system components (terrestrial ecosystems, hydrology, and the atmosphere) from that of an uncoupled model.

Engine Cycle Analysis for a Particle Bed Reactor Nuclear Rocket

DTIC Science & Technology

1991-03-01

0 DTIC USERS UNCLASSIFIED 22a. NAME OF RESPONSIBLE INDIVIDUAL ZZb. TELEPHONE (Include Area Code) 22c. OFFICE SYMBOL Lt Timothy J . Lawrence 805-275...Cycle with 2000 MW PBR and Uncooled Nozzle J : Output for Bleed Cycle with 2000 MW PBR and Cooled Nozzle K: Output for Expander Cycle with 2000 MW PBR L...Mars with carbon dioxide, the primary component of the Martian atmosphere. Carbon dioxide would delivera smaller ! j , but its use would eliminate the

γ-Oryzanol-Rich Black Rice Bran Extract Enhances the Innate Immune Response.

PubMed

Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Lim, Yoongho; Kim, Jung-Bong; Lee, Young Han

2017-09-01

The innate immune response is an important host primary defense system against pathogens. γ-Oryzanol is one of the nutritionally important phytoceutical components in rice bran oil. The goal of this study was to investigate the effect of γ-oryzanol-rich extract from black rice bran (γORE) on the activation of the innate immune system. In this study, we show that γORE increased the expression of CD14 and Toll-like receptor 4 and enhanced the phagocytic activity of RAW264.7 macrophages. Furthermore, γORE and its active ingredient γ-oryzanol promoted the secretion of innate cytokines, interleukin-8, and CCL2, which facilitate phagocytosis by RAW264.7 cells. These findings suggest that γ-oryzanol in the γORE enhances innate immune responses.

The influence of surround suppression on adaptation effects in primary visual cortex

PubMed Central

Wissig, Stephanie C.

2012-01-01

Adaptation, the prolonged presentation of stimuli, has been used to probe mechanisms of visual processing in physiological, imaging, and perceptual studies. Previous neurophysiological studies have measured adaptation effects by using stimuli tailored to evoke robust responses in individual neurons. This approach provides an incomplete view of how an adapter alters the representation of sensory stimuli by a population of neurons with diverse functional properties. We implanted microelectrode arrays in primary visual cortex (V1) of macaque monkeys and measured orientation tuning and contrast sensitivity in populations of neurons before and after prolonged adaptation. Whereas previous studies in V1 have reported that adaptation causes stimulus-specific suppression of responsivity and repulsive shifts in tuning preference, we have found that adaptation can also lead to response facilitation and shifts in tuning toward the adapter. To explain this range of effects, we have proposed and tested a simple model that employs stimulus-specific suppression in both the receptive field and the spatial surround. The predicted effects on tuning depend on the relative drive provided by the adapter to these two receptive field components. Our data reveal that adaptation can have a much richer repertoire of effects on neuronal responsivity and tuning than previously considered and suggest an intimate mechanistic relationship between spatial and temporal contextual effects. PMID:22423001

Influence of military component and deployment-related experiences on mental disorders among Canadian military personnel who deployed to Afghanistan: a cross-sectional survey

PubMed Central

Boulos, David; Fikretoglu, Deniz

2018-01-01

Objective The primary objective was to explore differences in mental health problems (MHP) between serving Canadian Armed Forces (CAF) components (Regular Force (RegF); Reserve Force (ResF)) with an Afghanistan deployment and to assess the contribution of both component and deployment experiences to MHP using covariate-adjusted prevalence difference estimates. Additionally, mental health services use (MHSU) was descriptively assessed among those with a mental disorder. Design Data came from the 2013 CAF Mental Health Survey, a cross-sectional survey of serving personnel (n=72 629). Analyses were limited to those with an Afghanistan deployment (population n=35 311; sampled n=4854). Logistic regression compared MHP between RegF and ResF members. Covariate-adjusted prevalence differences were computed. Primary outcome measure The primary outcomes were MHP, past-year mental disorders, identified using the WHO’s Composite International Diagnostic Interview, and past-year suicide ideation. Results ResF personnel were less likely to be identified with a past-year anxiety disorder (adjusted OR (AOR)=0.72 (95% CI 0.58 to 0.90)), specifically both generalised anxiety disorder and panic disorder, but more likely to be identified with a past-year alcohol abuse disorder (AOR=1.63 (95% CI 1.04 to 2.58)). The magnitude of the covariate-adjusted disorder prevalence differences for component was highest for the any anxiety disorder outcome, 2.8% (95% CI 1.0 to 4.6); lower for ResF. All but one deployment-related experience variable had some association with MHP. The ‘ever felt responsible for the death of a Canadian or ally personnel’ experience had the strongest association with MHP; its estimated covariate-adjusted disorder prevalence difference was highest for the any (of the six measured) mental disorder outcome (11.2% (95% CI 6.6 to 15.9)). Additionally, ResF reported less past-year MHSU and more past-year civilian MHSU. Conclusions Past-year MHP differences were identified between components. Our findings suggest that although deployment-related experiences were highly associated with MHP, these only partially accounted for MHP differences between components. Additional research is needed to further investigate MHSU differences between components. PMID:29530906

Biocompatibility tests of components of an implantable cardiac assist device.

PubMed

von Recum, A F; Imamura, H; Freed, P S; Kantrowitz, A; Chen, S T; Ekstrom, M E; Baechler, C A; Barnhart, M I

1978-09-01

A permanently implantable in-series left ventricular assist device, the dynamic aortic patch (DAP), has been tested in chronic animal experiments. The DAP replaces a section of the intrathoracic aortic wall. Hemothorax and hematocele at the implantation site have been complications in recent experiments. Primary postoperative hemorrhage was ruled out, and the biocompatibility of all components was therefore examined. Dacron velour, Teflon felt, conductive polyurethane, segmented polyether polyurethane, and Teflon-coated polyester fiber sutures were implanted in the pleural cavities of dogs and tested in vitro by culturing canine saphenous vein explants on them. In vivo experiments demonstrated that all components elicited mild to moderate inflammatory reactions, but hematocele occurred only when the components were implanted in the aorta with direct blood contact and exposed to arterial blood pressures. In vitro, cells were cultured on all components with no signs of toxic reactions. These results indicated that the host tolerated all implant components without major inflammatory responses. However, histological data indicated that chronic slow bleeding into or through the Dacron velour in contact with the arterial blood serum could account for hemothorax or hematocele formation. Therefore, a configuration of the assist device using materials impermeable to blood may obviate these difficulties.

Primary Surface Particle Motion as a Mechanism for YORP-Driven Binary Asteroid Evolution

NASA Astrophysics Data System (ADS)

Fahnestock, Eugene G.; Scheeres, D. J.

2008-09-01

Within the largest class of binary asteroid systems -- asynchronous binaries typified by 1999 KW4 -- we hypothesize continued YORP spin-up of the rapidly rotating primary leads to recurring episodic lofting motion of primary equator regolith. We theorize this is a mechanism for transporting YORP-injected angular momentum from primary spin into the mutual orbit. This both enables binary primaries to continue to spin at near surface fission rates and produces continued orbit expansion on time scales several times faster than expansion predicted by tidal dissipation alone. This is distinct from the Binary Yorp (BYORP) phenomenon, not studied in this work but to be added to it later. We evaluate our hypotheses using a combination of techniques for an example binary system. First high-fidelity dynamic simulation of surface-originating particles in the full-detail gravity field of the binary components, themselves propagated according to the full two body problem, gives particle final disposition (return impact, transfer impact, escape). Trajectory end states found for regolith lofted at different initial primary spin rates and relative poses are collected into probability matrices, allowing probabilistic propagation of surface particles for long durations at low computational cost. We track changes to mass, inertia dyad, rotation state, and centroid position and velocity for each component in response to this mapped particle motion. This allows tracking of primary, secondary, and mutual orbit angular momenta over time, clearly demonstrating the angular momentum transfer mechanism and validating our hypotheses. We present current orbit expansion rates and estimated orbit size doubling times consistent with this mechanism, for a few binary systems. We also discuss ramifications of this type of rapid binary evolution towards separation, including the frequency with which "divorced binaries" on similar heliocentric orbits are produced, formation of triple systems such as 2001 SN263, and separation timescale dependence on heliocentric distance.

Vestibular convergence patterns in vestibular nuclei neurons of alert primates

NASA Technical Reports Server (NTRS)

Dickman, J. David; Angelaki, Dora E.

2002-01-01

Sensory signal convergence is a fundamental and important aspect of brain function. Such convergence may often involve complex multidimensional interactions as those proposed for the processing of otolith and semicircular canal (SCC) information for the detection of translational head movements and the effective discrimination from physically congruent gravity signals. In the present study, we have examined the responses of primate rostral vestibular nuclei (VN) neurons that do not exhibit any eye movement-related activity using 0.5-Hz translational and three-dimensional (3D) rotational motion. Three distinct neural populations were identified. Approximately one-fourth of the cells exclusively encoded rotational movements (canal-only neurons) and were unresponsive to translation. The canal-only central neurons encoded head rotation in SCC coordinates, exhibited little orthogonal canal convergence, and were characterized with significantly higher sensitivities to rotation as compared to primary SCC afferents. Another fourth of the neurons modulated their firing rates during translation (otolith-only cells). During rotations, these neurons only responded when the axis of rotation was earth-horizontal and the head was changing orientation relative to gravity. The remaining one-half of VN neurons were sensitive to both rotations and translations (otolith + canal neurons). Unlike primary otolith afferents, however, central neurons often exhibited significant spatiotemporal (noncosine) tuning properties and a wide variety of response dynamics to translation. To characterize the pattern of SCC inputs to otolith + canal neurons, their rotational maximum sensitivity vectors were computed using exclusively responses during earth-vertical axis rotations (EVA). Maximum sensitivity vectors were distributed throughout the 3D space, suggesting strong convergence from multiple SCCs. These neurons were also tested with earth-horizontal axis rotations (EHA), which would activate both vertical canals and otolith organs. However, the recorded responses could not be predicted from a linear combination of EVA rotational and translational responses. In contrast, one-third of the neurons responded similarly during EVA and EHA rotations, although a significant response modulation was present during translation. Thus this subpopulation of otolith + canal cells, which included neurons with either high- or low-pass dynamics to translation, appear to selectively ignore the component of otolith-selective activation that is due to changes in the orientation of the head relative to gravity. Thus contrary to primary otolith afferents and otolith-only central neurons that respond equivalently to tilts relative to gravity and translational movements, approximately one-third of the otolith + canal cells seem to encode a true estimate of the translational component of the imposed passive head and body movement.

High frequency oscillations evoked by peripheral magnetic stimulation.

PubMed

Biller, S; Simon, L; Fiedler, P; Strohmeier, D; Haueisen, J

2011-01-01

The analysis of somatosensory evoked potentials (SEP) and / or fields (SEF) is a well-established and important tool for investigating the functioning of the peripheral and central human nervous system. A standard technique to evoke SEPs / SEFs is the stimulation of the median nerve by using a bipolar electrical stimulus. We aim at an alternative stimulation technique enabling stimulation of deep nerve structures while reducing patient stress and error susceptibility. In the current study, we apply a commercial transcranial magnetic stimulation system for peripheral magnetic stimulation of the median nerve. We compare the results of simultaneously recorded EEG signals to prove applicability of our technique to evoke SEPs including low frequency components (LFC) as well as high frequency oscillations (HFO). Therefore, we compare amplitude, latency and time-frequency characteristics of the SEP of 14 healthy volunteers after electric and magnetic stimulation. Both low frequency components and high frequency oscillations were detected. The HFOs were superimposed onto the primary cortical response N20. Statistical analysis revealed significantly lower amplitudes and increased latencies for LFC and HFO components after magnetic stimulation. The differences indicate the inability of magnetic stimulation to elicit supramaximal responses. A psycho-perceptual evaluation showed that magnetic stimulation was less unpleasant for 12 out of the 14 volunteers. In conclusion, we showed that LFC and HFO components related to median nerve stimulation can be evoked by peripheral magnetic stimulation.

Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

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

Kinsella, Paula, E-mail: paula.kinsella@dcu.ie; Howley, Rachel, E-mail: rhowley@rcsi.ie; Doolan, Padraig, E-mail: padraig.doolan@dcu.ie

2012-03-10

High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Responsemore » to TKIs was assessed using 50% inhibitory concentrations (IC{sub 50}). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-{alpha} expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: Black-Right-Pointing-Pointer Non-responders had low EGFR expression, high PDGFR-{beta}, and a low proliferation rate. Black-Right-Pointing-Pointer PTEN is not indicative of response to a TKI. Black-Right-Pointing-Pointer Erlotinib response was not associated with expression of the proteins examined. Black-Right-Pointing-Pointer Imatinib-response correlated with expression of PDGFR-{alpha}. Black-Right-Pointing-Pointer Gefitinib response correlated with increased expression of EGFR.« less

Capsular Polysaccharide is a Main Component of Mycoplasma ovipneumoniae in the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells

PubMed Central

Jiang, Zhongjia; Song, Fuyang; Li, Yanan; Xue, Di; Deng, Guangcun; Li, Min

2017-01-01

Mycoplasma ovipneumoniae (M. ovipneumoniae) is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invading M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS) of M. ovipneumoniae using sheep bronchial epithelial cells cultured in an air-liquid interface (ALI) model. Results showed that CPS derived from M. ovipneumoniae could activate toll-like receptor- (TLR-) mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor 3 (IRF3) as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1β, TNFα, and IL8, and anti-inflammatory cytokines such as IL10 and TGFβ of TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction of M. ovipneumoniae-induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component of M. ovipneumoniae, which may play a crucial role in the inflammatory response induced by M. ovipneumoniae infections. PMID:28553017

Responses of antennal olfactory receptors in the yellow fever mosquito Aedes aegypti to human body odours.

PubMed

Pappenberger, B; Geier, M; Boeckh, J

1996-01-01

Recent behavioural studies have demonstrated that human body odours which female Aedes aegypti find attractive exert their effects as complex mixtures of synergistically acting components. We have attempted to clarify the sensory mechanisms underlying the perception of these complex host odours by studying the responses of sensory cells underneath the A3-type sensilla of the mosquito antenna to both a human skin wash extract and the extract's active chromatographic fractions. The reaction patterns show that the host stimuli elicit responses from several types of receptor cells in a typical across-fibre pattern mode. It seems as if this is another case where the essential message in a biologically significant odour consists of a complex pattern of compounds that is encoded in an according complex response pattern by a cooperating set of primary sensory neurons of different odour specificities.

Biogeochemical carbon coupling influences global precipitation in geoengineering experiments

NASA Astrophysics Data System (ADS)

Fyfe, J. C.; Cole, J. N. S.; Arora, V. K.; Scinocca, J. F.

2013-02-01