Academic Boot Camp for the Writing of Psychology Research Reports

ERIC Educational Resources Information Center

Skues, Jason L.; Wise, Lisa

2014-01-01

Herein, we describe the implementation of, and responses to, a structured writing workshop in the form of an academic boot camp. Participants were 42 undergraduate psychology students from a medium-sized Australian university who were completing their major assignment for the semester. A majority of the students expressed satisfaction with the…

Cyberbullying: A Study of School Administrators' Perceptions and Responses to Online Aggression

ERIC Educational Resources Information Center

Hasenstab, Jean Jegglin

2012-01-01

This qualitative, phenomenological study examined the perspectives and responses of twelve school administrators who have responded to cyberbullying with a disciplinary action. The majority of the data collected for this study was gathered through individual semi-structured interviews. Supporting documentation such as entries in a reflective…

An Investigation of the Linkage between Technology-Based Activities and STEM Major Selection in 4-Year Postsecondary Institutions in the United States: Multilevel Structural Equation Modelling

ERIC Educational Resources Information Center

Lee, Ahlam

2015-01-01

Among the disciplines of science, technology, engineering, and math (STEM), much attention has been paid to the influences of math- and science-related learning contexts on students' STEM major selection. However, the technology and engineering learning contexts that are linked to STEM major selection have been overlooked. In response, a…

Analysis of Army Transformation and the Effects on Customer Ordering Behavior

DTIC Science & Technology

2007-03-01

operational scenarios ( Caldera and Shinseki, 2000:3). A responsive and agile force requires a responsive and agile logistics structure. The Army...assistance, disaster relief, peace-keeping, peace-making, and major theater wars ( Caldera and Shinseki, 2000:3). In fact, since 1995, the U.S. Army has...must be responsive, deployable, agile, versatile, lethal, survivable, and sustainable ( Caldera and Shinseki, 2000:4-5). Logistics Transformation

An Adaptive Evaluation Structure for Computer-Based Instruction.

ERIC Educational Resources Information Center

Welsh, William A.

Adaptive Evaluation Structure (AES) is a set of linked computer programs designed to increase the effectiveness of interactive computer-assisted instruction at the college level. The package has four major features, the first of which is based on a prior cognitive inventory and on the accuracy and pace of student responses. AES adjusts materials…

Structure ignition assessment model (SIAM)\\t

Treesearch

Jack D. Cohen

1995-01-01

Major wildland/urban interface fire losses, principally residences, continue to occur. Although the problem is not new, the specific mechanisms are not well known on how structures ignite in association with wildland fires. In response to the need for a better understanding of wildland/urban interface ignition mechanisms and a method of assessing the ignition risk,...

Alumni Perceptions: A Test of NCHEMS' Outcomes Structure. AIR Forum 1981 Paper.

ERIC Educational Resources Information Center

McLaughlin, Gerald W.; And Others

A theoretical taxonomy of student outcomes based on the National Center for Higher Education Management Systems' (NCHEMS) structure was investigated using survey responses from 1,833 alumni of a comprehensive state university. The alumni spanned 45 class years and four major curricular types: applied science, business, engineering, and qualitative…

Nanocomposites for Electronic Applications

DTIC Science & Technology

1989-09-30

response. In the tungsten bronze structure relaxors a major breakthrough is the clear documentation of spin glass behaviour in an already polar matrix, for...MPB) this behaviour is seen in both ferroelectric tetragonal and orthorhombic species.

Adaptive responses and disruptive effects: how major wildfire influences kinship-based social interactions in a forest marsupial.

PubMed

Banks, Sam C; Blyton, Michaela D J; Blair, David; McBurney, Lachlan; Lindenmayer, David B

2012-02-01

Environmental disturbance is predicted to play a key role in the evolution of animal social behaviour. This is because disturbance affects key factors underlying social systems, such as demography, resource availability and genetic structure. However, because natural disturbances are unpredictable there is little information on their effects on social behaviour in wild populations. Here, we investigated how a major wildfire affected cooperation (sharing of hollow trees) by a hollow-dependent marsupial. We based two alternative social predictions on the impacts of fire on population density, genetic structure and resources. We predicted an adaptive social response from previous work showing that kin selection in den-sharing develops as competition for den resources increases. Thus, kin selection should occur in burnt areas because the fire caused loss of the majority of hollow-bearing trees, but no detectable mortality. Alternatively, fire may have a disruptive social effect, whereby postfire home range-shifts 'neutralize' fine-scale genetic structure, thereby removing opportunities for kin selection between neighbours. Both predictions occurred: the disruptive social effect in burnt habitat and the adaptive social response in adjacent unburnt habitat. The latter followed a massive demographic influx to unburnt 'refuge' habitat that increased competition for dens, leading to a density-related kin selection response. Our results show remarkable short-term plasticity of animal social behaviour and demonstrate how the social effects of disturbance extend into undisturbed habitat owing to landscape-scale demographic shifts. We predicted long-term changes in kinship-based cooperative behaviour resulting from the genetic and resource impacts of forecast changes to fire regimes in these forests. © 2011 Blackwell Publishing Ltd.

Response of Fuelbed Characteristics to Restoration Treatments in Pinyon-Juniper-Encroached Shrublands on the Shivwits Plateau, Arizona

Treesearch

Helen Y. Smith; Sharon Hood; Matt Brooks; JR Matchett; Curt Deuser

2006-01-01

The recent encroachment of piñon (Pinus edulis) and juniper trees (Juniperus osteosperma) into historically shrub- and grass-dominated landscapes has caused major changes in ecosystem structure and function, including dramatic changes in fuel structure and fire regimes. Such encroachment is currently occurring on thousands of acres...

Temperature-responsive in vitro RNA structurome of Yersinia pseudotuberculosis.

PubMed

Righetti, Francesco; Nuss, Aaron M; Twittenhoff, Christian; Beele, Sascha; Urban, Kristina; Will, Sebastian; Bernhart, Stephan H; Stadler, Peter F; Dersch, Petra; Narberhaus, Franz

2016-06-28

RNA structures are fundamentally important for RNA function. Dynamic, condition-dependent structural changes are able to modulate gene expression as shown for riboswitches and RNA thermometers. By parallel analysis of RNA structures, we mapped the RNA structurome of Yersinia pseudotuberculosis at three different temperatures. This human pathogen is exquisitely responsive to host body temperature (37 °C), which induces a major metabolic transition. Our analysis profiles the structure of more than 1,750 RNAs at 25 °C, 37 °C, and 42 °C. Average mRNAs tend to be unstructured around the ribosome binding site. We searched for 5'-UTRs that are folded at low temperature and identified novel thermoresponsive RNA structures from diverse gene categories. The regulatory potential of 16 candidates was validated. In summary, we present a dynamic bacterial RNA structurome and find that the expression of virulence-relevant functions in Y. pseudotuberculosis and reprogramming of its metabolism in response to temperature is associated with a restructuring of numerous mRNAs.

The Effects of Foam Thermal Protection System on the Damage Tolerance Characteristics of Composite Sandwich Structures for Launch Vehicles

NASA Technical Reports Server (NTRS)

Nettles, A. T.; Hodge, A. J.; Jackson, J. R.

2011-01-01

For any structure composed of laminated composite materials, impact damage is one of the greatest risks and therefore most widely tested responses. Typically, impact damage testing and analysis assumes that a solid object comes into contact with the bare surface of the laminate (the outer ply). However, most launch vehicle structures will have a thermal protection system (TPS) covering the structure for the majority of its life. Thus, the impact response of the material with the TPS covering is the impact scenario of interest. In this study, laminates representative of the composite interstage structure for the Ares I launch vehicle were impact tested with and without the planned TPS covering, which consists of polyurethane foam. Response variables examined include maximum load of impact, damage size as detected by nondestructive evaluation techniques, and damage morphology and compression after impact strength. Results show that there is little difference between TPS covered and bare specimens, except the residual strength data is higher for TPS covered specimens.

Aeroelastic Modeling of a Nozzle Startup Transient

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Zhao, Xiang; Zhang, Sijun; Chen, Yen-Sen

2014-01-01

Lateral nozzle forces are known to cause severe structural damage to any new rocket engine in development during test. While three-dimensional, transient, turbulent, chemically reacting computational fluid dynamics methodology has been demonstrated to capture major side load physics with rigid nozzles, hot-fire tests often show nozzle structure deformation during major side load events, leading to structural damages if structural strengthening measures were not taken. The modeling picture is incomplete without the capability to address the two-way responses between the structure and fluid. The objective of this study is to develop a tightly coupled aeroelastic modeling algorithm by implementing the necessary structural dynamics component into an anchored computational fluid dynamics methodology. The computational fluid dynamics component is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, while the computational structural dynamics component is developed under the framework of modal analysis. Transient aeroelastic nozzle startup analyses at sea level were performed, and the computed transient nozzle fluid-structure interaction physics presented,

Changes in light intensity reveal a major role for carbon balance in Arabidopsis responses to high temperature.

PubMed

Vasseur, François; Pantin, Florent; Vile, Denis

2011-09-01

High temperature (HT) is a major limiting factor for plant productivity. Because some responses to HT, notably hyponasty, resemble those encountered in low light (LL), we hypothesized that plant responses to HT are under the control of carbon balance. We analysed the interactive effects of HT and irradiance level on hyponasty and a set of traits related to plant growth in natural accessions of Arabidopsis thaliana and mutants affected in heat dissipation through transpiration (NCED6-OE, ost2) and starch metabolism (pgm). HT induced hyponasty, reduced plant growth and modified leaf structure. LL worsened the effects of HT, while increasing light restored trait values close to levels observed at control temperature. Leaf temperature per se did not play a major role in the observed responses. By contrast, a major role of carbon balance was supported by hyponastic growth of pgm, as well as morphological, physiological (photosynthesis, sugar and starch contents) and transcriptional data. Carbon balance could be a common sensor of HT and LL, leading to responses specific of the shade avoidance syndrome. Hyponasty and associated changes in plant traits could be key traits conditioning plant performance under competition for light, particularly in warm environments. © 2011 Blackwell Publishing Ltd.

Implications of Mycobacterium Major Facilitator Superfamily for Novel Measures against Tuberculosis.

PubMed

Wang, Rui; Zhang, Zhen; Xie, Longxiang; Xie, Jianping

2015-01-01

Major facilitator superfamily (MFS) is an important secondary membrane transport protein superfamily conserved from prokaryotes to eukaryotes. The MFS proteins are widespread among bacteria and are responsible for the transfer of substrates. Pathogenic Mycobacterium MFS transporters, their distribution, function, phylogeny, and predicted crystal structures were studied to better understand the function of MFS and to discover specific inhibitors of MFS for better tuberculosis control.

Mathematical investigation of IP3-dependent calcium dynamics in astrocytes.

PubMed

Handy, Gregory; Taheri, Marsa; White, John A; Borisyuk, Alla

2017-06-01

We study evoked calcium dynamics in astrocytes, a major cell type in the mammalian brain. Experimental evidence has shown that such dynamics are highly variable between different trials, cells, and cell subcompartments. Here we present a qualitative analysis of a recent mathematical model of astrocyte calcium responses. We show how the major response types are generated in the model as a result of the underlying bifurcation structure. By varying key channel parameters, mimicking blockers used by experimentalists, we manipulate this underlying bifurcation structure and predict how the distributions of responses can change. We find that store-operated calcium channels, plasma membrane bound channels with little activity during calcium transients, have a surprisingly strong effect, underscoring the importance of considering these channels in both experiments and mathematical settings. Variation in the maximum flow in different calcium channels is also shown to determine the range of stable oscillations, as well as set the range of frequencies of the oscillations. Further, by conducting a randomized search through the parameter space and recording the resulting calcium responses, we create a database that can be used by experimentalists to help estimate the underlying channel distribution of their cells.

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

Replacement of the Endogenous Starch Debranching Enzymes ISA1 and ISA2 of Arabidopsis with the Rice Orthologs Reveals a Degree of Functional Conservation during Starch Synthesis

PubMed Central

Streb, Sebastian; Zeeman, Samuel C.

2014-01-01

This study tested the interchangeability of enzymes in starch metabolism between dicotyledonous and monocotyledonous plant species. Amylopectin - a branched glucose polymer - is the major component of starch and is responsible for its semi-crystalline property. Plants synthesize starch with distinct amylopectin structures, varying between species and tissues. The structure determines starch properties, an important characteristic for cooking and nutrition, and for the industrial uses of starch. Amylopectin synthesis involves at least three enzyme classes: starch synthases, branching enzymes and debranching enzymes. For all three classes, several enzyme isoforms have been identified. However, it is not clear which enzyme(s) are responsible for the large diversity of amylopectin structures. Here, we tested whether the specificities of the debranching enzymes (ISA1 and ISA2) are major determinants of species-dependent differences in amylopectin structure by replacing the dicotyledonous Arabidopsis isoamylases (AtISA1 and AtISA2) with the monocotyledonous rice (Oryza sativa) isoforms. We demonstrate that the ISA1 and ISA2 are sufficiently well conserved between these species to form heteromultimeric chimeric Arabidopsis/rice isoamylase enzymes. Furthermore, we were able to reconstitute the endosperm-specific rice OsISA1 homomultimeric complex in Arabidopsis isa1isa2 mutants. This homomultimer was able to facilitate normal rates of starch synthesis. The resulting amylopectin structure had small but significant differences in comparison to wild-type Arabidopsis amylopectin. This suggests that ISA1 and ISA2 have a conserved function between plant species with a major role in facilitating the crystallization of pre-amylopectin synthesized by starch synthases and branching enzymes, but also influencing the final structure of amylopectin. PMID:24642810

Smart wormlike micelles.

PubMed

Chu, Zonglin; Dreiss, Cécile A; Feng, Yujun

2013-09-07

A major scientific challenge of the past decade pertaining to the field of soft matter has been to craft 'adaptable' materials, inspired by nature, which can dynamically alter their structure and functionality on demand, in response to triggers produced by environmental changes. Amongst these, 'smart' surfactant wormlike micelles, responsive to external stimuli, are a particularly recent area of development, yet highly promising, given the versatility of the materials but simplicity of the design-relying on small amphiphilic molecules and their spontaneous self-assembly. The switching 'on' and 'off' of the micellar assembly structures has been reported using electrical, optical, thermal or pH triggers and is now envisaged for multiple stimuli. The structural changes, in turn, can induce major variations in the macroscopic characteristics, affecting properties such as viscosity and elasticity and sometimes even leading to a spontaneous and effective 'sol-gel' transition. These original smart materials based on wormlike micelles have been successfully used in the oil industry, and offer a significant potential in a wide range of other technological applications, including biomedicine, cleaning processes, drag reduction, template synthesis, to name but a few. This review will report results in this field published over the last few years, describe the potential and practical applications of stimuli-responsive wormlike micelles and point out future challenges.

Development of an Aeroelastic Modeling Capability for Transient Nozzle Side Load Analysis

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Zhao, Xiang; Zhang, Sijun; Chen, Yen-Sen

2013-01-01

Lateral nozzle forces are known to cause severe structural damage to any new rocket engine in development during test. While three-dimensional, transient, turbulent, chemically reacting computational fluid dynamics methodology has been demonstrated to capture major side load physics with rigid nozzles, hot-fire tests often show nozzle structure deformation during major side load events, leading to structural damages if structural strengthening measures were not taken. The modeling picture is incomplete without the capability to address the two-way responses between the structure and fluid. The objective of this study is to develop a coupled aeroelastic modeling capability by implementing the necessary structural dynamics component into an anchored computational fluid dynamics methodology. The computational fluid dynamics component is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, while the computational structural dynamics component is developed in the framework of modal analysis. Transient aeroelastic nozzle startup analyses of the Block I Space Shuttle Main Engine at sea level were performed. The computed results from the aeroelastic nozzle modeling are presented.

Automated wind load characterization of wind turbine structures by embedded model updating

NASA Astrophysics Data System (ADS)

Swartz, R. Andrew; Zimmerman, Andrew T.; Lynch, Jerome P.

2010-04-01

The continued development of renewable energy resources is for the nation to limit its carbon footprint and to enjoy independence in energy production. Key to that effort are reliable generators of renewable energy sources that are economically competitive with legacy sources. In the area of wind energy, a major contributor to the cost of implementation is large uncertainty regarding the condition of wind turbines in the field due to lack of information about loading, dynamic response, and fatigue life of the structure expended. Under favorable circumstances, this uncertainty leads to overly conservative designs and maintenance schedules. Under unfavorable circumstances, it leads to inadequate maintenance schedules, damage to electrical systems, or even structural failure. Low-cost wireless sensors can provide more certainty for stakeholders by measuring the dynamic response of the structure to loading, estimating the fatigue state of the structure, and extracting loading information from the structural response without the need of an upwind instrumentation tower. This study presents a method for using wireless sensor networks to estimate the spectral properties of a wind turbine tower loading based on its measured response and some rudimentary knowledge of its structure. Structural parameters are estimated via model-updating in the frequency domain to produce an identification of the system. The updated structural model and the measured output spectra are then used to estimate the input spectra. Laboratory results are presented indicating accurate load characterization.

Necessary Conditions for Intraplate Seismic Zones in North America

NASA Astrophysics Data System (ADS)

Thomas, William A.; Powell, Christine A.

2017-12-01

The cause of intraplate seismic zones persists as an important scientific and societal question. Most intraplate earthquakes are concentrated in specific seismic zones along or adjacent to large-scale basement structures (e.g., rifts or sutures at ancient plate boundaries) within continental crust. The major intraplate seismic zones are limited to specific segments and are not distributed along the lengths of the ancient structures. We present a new hypothesis that major intraplate seismic zones are restricted to places where concentrated crustal deformation (CCD) is overprinted on large-scale basement structures. Examples where CCD affects the stability of specific parts of large-scale structures in response to present-day stress conditions include the most active seismic zones in central and eastern North America: Charlevoix, Eastern Tennessee, and New Madrid. Our hypothesis has important implications for the assessment of seismic hazards.

Management of the Space Physics Analysis Network (SPAN)

NASA Technical Reports Server (NTRS)

Green, James L.; Thomas, Valerie L.; Butler, Todd F.; Peters, David J.; Sisson, Patricia L.

1990-01-01

Here, the purpose is to define the operational management structure and to delineate the responsibilities of key Space Physics Analysis Network (SPAN) individuals. The management structure must take into account the large NASA and ESA science research community by giving them a major voice in the operation of the system. Appropriate NASA and ESA interfaces must be provided so that there will be adequate communications facilities available when needed. Responsibilities are delineated for the Advisory Committee, the Steering Committee, the Project Scientist, the Project Manager, the SPAN Security Manager, the Internetwork Manager, the Network Operations Manager, the Remote Site Manager, and others.

Transplant organizational structures: viewpoints from established centers.

PubMed

Abouljoud, M; Klintmalm, G; Whitehouse, S

2012-10-01

This personal viewpoint report summarizes the responses of a survey targeting established transplant programs with a structured framework, such as center, institute, or department, and stability of leadership to assure valuable experiential observations. The 18-item survey was sent to 20 US institutions that met inclusion criteria. The response rate was 100%. Seventeen institutions had a distinct transplant governance structure. A majority of respondents perceived that their type of transplant structure was associated with enhanced recognition within their institution (85%), improved regulatory compliance (85%), transplant volume growth (75%), improved quality outcomes (75%) and increased funding for transplant-related research (75%). The prevailing themes in respondents' remarks were the perceived need for autonomy of the transplant entity, alignment among services and finances and alignment of authority with responsibility. Many respondents suggested that a dialogue be opened about effective transplant infrastructure that overcomes the boundaries of traditional academic department silos. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

A Robust Response of Precipitation to Global Warming from CMIP5 Models

NASA Technical Reports Server (NTRS)

Lau, K. -M.; Wu, H. -T.; Kim, K. -M.

2012-01-01

How precipitation responds to global warming is a major concern to society and a challenge to climate change research. Based on analyses of rainfall probability distribution functions of 14 state-of-the-art climate models, we find a robust, canonical global rainfall response to a triple CO2 warming scenario, featuring 100 250% more heavy rain, 5-10% less moderate rain, and 10-15% more very light or no-rain events. Regionally, a majority of the models project a consistent response with more heavy rain events over climatologically wet regions of the deep tropics, and more dry events over subtropical and tropical land areas. Results suggest that increased CO2 emissions induce basic structural changes in global rain systems, increasing risks of severe floods and droughts in preferred geographic locations worldwide.

Thermal structure analyses for CSM testbed (COMET)

NASA Technical Reports Server (NTRS)

Xue, David Y.; Mei, Chuh

1994-01-01

This document is the final report for the project entitled 'Thermal Structure Analyses for CSM Testbed (COMET),' for the period of May 16, 1992 - August 15, 1994. The project was focused on the investigation and development of finite element analysis capability of the computational structural mechanics (CSM) testbed (COMET) software system in the field of thermal structural responses. The stages of this project consisted of investigating present capabilities, developing new functions, analysis demonstrations, and research topics. The appendices of this report list the detailed documents of major accomplishments and demonstration runstreams for future references.

Structural Dynamic Behavior of Wind Turbines

NASA Technical Reports Server (NTRS)

Thresher, Robert W.; Mirandy, Louis P.; Carne, Thomas G.; Lobitz, Donald W.; James, George H. III

2009-01-01

The structural dynamicist s areas of responsibility require interaction with most other members of the wind turbine project team. These responsibilities are to predict structural loads and deflections that will occur over the lifetime of the machine, ensure favorable dynamic responses through appropriate design and operational procedures, evaluate potential design improvements for their impact on dynamic loads and stability, and correlate load and control test data with design predictions. Load prediction has been a major concern in wind turbine designs to date, and it is perhaps the single most important task faced by the structural dynamics engineer. However, even if we were able to predict all loads perfectly, this in itself would not lead to an economic system. Reduction of dynamic loads, not merely a "design to loads" policy, is required to achieve a cost-effective design. The two processes of load prediction and structural design are highly interactive: loads and deflections must be known before designers and stress analysts can perform structural sizing, which in turn influences the loads through changes in stiffness and mass. Structural design identifies "hot spots" (local areas of high stress) that would benefit most from dynamic load alleviation. Convergence of this cycle leads to a turbine structure that is neither under-designed (which may result in structural failure), nor over-designed (which will lead to excessive weight and cost).

Structural response of transport airplanes in crash situations

NASA Technical Reports Server (NTRS)

Thomson, R. G.; Caiafa, C.

1983-01-01

This report highlights the results of contractural studies of transport accident data undertaken in a joint research program sponsored by the FAA and NASA. From these accident data studies it was concluded that the greatest potential for improved transport crashworthiness is in the reduction of fire related fatalities. Accident data pertaining to fuselage integrity, main landing gear collapse, fuel tank rupture, wing breaks, tearing of tank lower surfaces, and engine pod scrubbing are discussed. In those accidents where the energy absorbing protective capability of the fuselage structure is expended and the airplane experiences major structural damage, trauma caused fatalities are also discussed. The dynamic performance of current seat/restraint systems are examined but it is concluded that the accident data does not adequately define the relationship between occupant response and the dynamic interaction with the seat, floor and fuselage structure.

Item response theory analysis of the Utrecht Work Engagement Scale for Students (UWES-S) using a sample of Japanese university and college students majoring medical science, nursing, and natural science.

PubMed

Tsubakita, Takashi; Shimazaki, Kazuyo; Ito, Hiroshi; Kawazoe, Nobuo

2017-10-30

The Utrecht Work Engagement Scale for Students has been used internationally to assess students' academic engagement, but it has not been analyzed via item response theory. The purpose of this study was to conduct an item response theory analysis of the Japanese version of the Utrecht Work Engagement Scale for Students translated by authors. Using a two-parameter model and Samejima's graded response model, difficulty and discrimination parameters were estimated after confirming the factor structure of the scale. The 14 items on the scale were analyzed with a sample of 3214 university and college students majoring medical science, nursing, or natural science in Japan. The preliminary parameter estimation was conducted with the two parameter model, and indicated that three items should be removed because there were outlier parameters. Final parameter estimation was conducted using the survived 11 items, and indicated that all difficulty and discrimination parameters were acceptable. The test information curve suggested that the scale better assesses higher engagement than average engagement. The estimated parameters provide a basis for future comparative studies. The results also suggested that a 7-point Likert scale is too broad; thus, the scaling should be modified to fewer graded scaling structure.

Monitoring Interactions Inside Cells by Advanced Spectroscopies: Overview of Copper Transporters and Cisplatin.

PubMed

Lasorsa, Alessia; Natile, Giovanni; Rosato, Antonio; Tadini-Buoninsegni, Francesco; Arnesano, Fabio

2018-02-12

Resistance, either at the onset of the treatment or developed after an initial positive response, is a major limitation of antitumor therapy. In the case of platinum- based drugs, copper transporters have been found to interfere with drug trafficking by facilitating the import or favoring the platinum export and inactivation. The use of powerful spectroscopic, spectrometric and computational methods has allowed a deep structural insight into the mode of interaction of platinum drugs with the metal-binding domains of the transporter proteins. This review article focuses on the mode in which platinum drugs can compete with copper ion for binding to transport proteins and consequent structural and biological effects. Three types of transporters are discussed in detail: copper transporter 1 (Ctr1), the major responsible for Cu+ uptake; antioxidant-1 copper chaperone (Atox1), responsible for copper transfer within the cytoplasm; and copper ATPases (ATP7A/B), responsible for copper export into specific subcellular compartments and outside the cell. The body of knowledge summarized in this review can help in shaping current chemotherapy to optimize the efficacy of platinum drugs (particularly in relation to resistance) and to mitigate adverse effects on copper metabolism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

STAGS Developments for Residual Strength Analysis Methods for Metallic Fuselage Structures

NASA Technical Reports Server (NTRS)

Young, Richard D.; Rose, Cheryl A.

2014-01-01

A summary of advances in the Structural Analysis of General Shells (STAGS) finite element code for the residual strength analysis of metallic fuselage structures, that were realized through collaboration between the structures group at NASA Langley, and Dr. Charles Rankin is presented. The majority of the advancements described were made in the 1990's under the NASA Airframe Structural Integrity Program (NASIP). Example results from studies that were conducted using the STAGS code to develop improved understanding of the nonlinear response of cracked fuselage structures subjected to combined loads are presented. An integrated residual strength analysis methodology for metallic structure that models crack growth to predict the effect of cracks on structural integrity is demonstrated

Preoutbreak dynamics of a recently established invasive herbivore: roles of natural enemies and habitat structure in stage-specific performance of gypsy moth (Lepidoptera: Lymantriidae) populations in northeastern Wisconsin

Treesearch

Rebecca Hoffman Gray; Craig G. Lorimer; Patrick C. Tobin; Kenneth F. Raffa

2008-01-01

A major challenge to addressing biological invasions is that the need for emergency responses often precludes opportunities to analyze the dynamics between initial establishment and population eruption. Thus, a broader understanding of underlying processes and management opportunities is often lacking. We examined the effects of habitat structure and natural enemies on...

Citizen sensors for SHM: use of accelerometer data from smartphones.

PubMed

Feng, Maria; Fukuda, Yoshio; Mizuta, Masato; Ozer, Ekin

2015-01-29

Ubiquitous smartphones have created a significant opportunity to form a low-cost wireless Citizen Sensor network and produce big data for monitoring structural integrity and safety under operational and extreme loads. Such data are particularly useful for rapid assessment of structural damage in a large urban setting after a major event such as an earthquake. This study explores the utilization of smartphone accelerometers for measuring structural vibration, from which structural health and post-event damage can be diagnosed. Widely available smartphones are tested under sinusoidal wave excitations with frequencies in the range relevant to civil engineering structures. Large-scale seismic shaking table tests, observing input ground motion and response of a structural model, are carried out to evaluate the accuracy of smartphone accelerometers under operational, white-noise and earthquake excitations of different intensity. Finally, the smartphone accelerometers are tested on a dynamically loaded bridge. The extensive experiments show satisfactory agreements between the reference and smartphone sensor measurements in both time and frequency domains, demonstrating the capability of the smartphone sensors to measure structural responses ranging from low-amplitude ambient vibration to high-amplitude seismic response. Encouraged by the results of this study, the authors are developing a citizen-engaging and data-analytics crowdsourcing platform towards a smartphone-based Citizen Sensor network for structural health monitoring and post-event damage assessment applications.

Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building.

PubMed

Cha, Young-Jin; Trocha, Peter; Büyüköztürk, Oral

2016-07-01

Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA), was characterized and modeled as a simplified lumped-mass beam model (SLMM), using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA). Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement.

Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building

PubMed Central

Cha, Young-Jin; Trocha, Peter; Büyüköztürk, Oral

2016-01-01

Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA), was characterized and modeled as a simplified lumped-mass beam model (SLMM), using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA). Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement. PMID:27376303

Implementation of structural response sensitivity calculations in a large-scale finite-element analysis system

NASA Technical Reports Server (NTRS)

Giles, G. L.; Rogers, J. L., Jr.

1982-01-01

The methodology used to implement structural sensitivity calculations into a major, general-purpose finite-element analysis system (SPAR) is described. This implementation includes a generalized method for specifying element cross-sectional dimensions as design variables that can be used in analytically calculating derivatives of output quantities from static stress, vibration, and buckling analyses for both membrane and bending elements. Limited sample results for static displacements and stresses are presented to indicate the advantages of analytically calculating response derivatives compared to finite difference methods. Continuing developments to implement these procedures into an enhanced version of SPAR are also discussed.

RCM as a Catalyst.

ERIC Educational Resources Information Center

West, J. Anthony; Seidita, Vincent; Di Mattia, Judy; Whalen, Edward L.

1997-01-01

A study by the National Association of College and University Business Officers surveyed member institutions (n=235) about the use and effectiveness of responsibility center management (RCM) on campus. Results indicate private colleges are more likely to use RCM. Major areas of concern include organizational structure, financial information for…

Characterization of Aircraft Structural Damage Using Guided Wave Based Finite Element Analysis for In-Flight Structural Health Management

NASA Technical Reports Server (NTRS)

Seshadri, Banavara R.; Krishnamurthy, Thiagarajan; Ross, Richard W.

2016-01-01

The development of multidisciplinary Integrated Vehicle Health Management (IVHM) tools will enable accurate detection, diagnosis and prognosis of damage under normal and adverse conditions during flight. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable catastrophic propagation of damage during a flight, load levels must be maintained that are below the load-carrying capacity for damaged aircraft structures. Hence, a capability is needed for accurate real-time predictions of safe load carrying capacity for aircraft structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size and location is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size and location is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries and sizes.

Immunoevasive Aspergillus virulence factors.

PubMed

Chotirmall, Sanjay H; Mirkovic, Bojana; Lavelle, Gillian M; McElvaney, Noel G

2014-12-01

Individuals with structural lung disease or defective immunity are predisposed to Aspergillus-associated disease. Manifestations range from allergic to cavitary or angio-invasive syndromes. Despite daily spore inhalation, immunocompetence facilitates clearance through initiation of innate and adaptive host responses. These include mechanical barriers, phagocyte activation, antimicrobial peptide release and pattern recognition receptor activation. Adaptive responses include Th1 and Th2 approaches. Understanding Aspergillus virulence mechanisms remains critical to the development of effective research and treatment strategies to counteract the fungi. Major virulence factors relate to fungal structure, protease release and allergens; however, mechanisms utilized to evade immune recognition continue to be important in establishing infection. These include the fungal rodlet layer, dihydroxynaphthalene-melanin, detoxifying systems for reactive oxygen species and toxin release. One major immunoevasive toxin, gliotoxin, plays a key role in mediating Aspergillus-associated colonization in the context of cystic fibrosis. Here, it down-regulates vitamin D receptor expression which following itraconazole therapy is rescued concurrent with decreased Th2 cytokine (IL-5 and IL-13) concentrations in the CF airway. This review focuses on the interaction between Aspergillus pathogenic mechanisms, host immune responses and the immunoevasive strategies employed by the organism during disease states such as that observed in cystic fibrosis.

Scleral anisotropy and its effects on the mechanical response of the optic nerve head

PubMed Central

Coudrillier, Baptiste; Boote, Craig; Quigley, Harry A.

2012-01-01

This paper presents a computational modeling study of the effects of the collagen fiber structure on the mechanical response of the sclera and the adjacent optic nerve head (ONH). A specimen-specific inverse finite element method was developed to determine the material properties of two human sclera subjected to full-field inflation experiments. A distributed fiber model was applied to describe the anisotropic elastic behavior of the sclera. The model directly incorporated wide angle x-ray scattering measurements of the anisotropic collagen structure. The converged solution of the inverse method was used in micromechanical studies of the mechanical anisotropy of the sclera at different scales. The effects of the scleral collagen fiber structure on the ONH deformation were evaluated by progressively filtering out local anisotropic features. It was found that the majority of the midposterior sclera could be described as isotropic without significantly affecting the mechanical response of the tissues of the ONH. In contrast, removing local anisotropic features in the peripapillary sclera produced significant changes in scleral canal expansion, and lamina cribrosa deformation. Local variations in the collagen structure of the peripapillary sclera significantly influenced the mechanical response of the ONH. PMID:23188256

The role of emotion in musical improvisation: an analysis of structural features.

PubMed

McPherson, Malinda J; Lopez-Gonzalez, Monica; Rankin, Summer K; Limb, Charles J

2014-01-01

One of the primary functions of music is to convey emotion, yet how music accomplishes this task remains unclear. For example, simple correlations between mode (major vs. minor) and emotion (happy vs. sad) do not adequately explain the enormous range, subtlety or complexity of musically induced emotions. In this study, we examined the structural features of unconstrained musical improvisations generated by jazz pianists in response to emotional cues. We hypothesized that musicians would not utilize any universal rules to convey emotions, but would instead combine heterogeneous musical elements together in order to depict positive and negative emotions. Our findings demonstrate a lack of simple correspondence between emotions and musical features of spontaneous musical improvisation. While improvisations in response to positive emotional cues were more likely to be in major keys, have faster tempos, faster key press velocities and more staccato notes when compared to negative improvisations, there was a wide distribution for each emotion with components that directly violated these primary associations. The finding that musicians often combine disparate features together in order to convey emotion during improvisation suggests that structural diversity may be an essential feature of the ability of music to express a wide range of emotion.

The Role of Emotion in Musical Improvisation: An Analysis of Structural Features

PubMed Central

McPherson, Malinda J.; Lopez-Gonzalez, Monica; Rankin, Summer K.; Limb, Charles J.

2014-01-01

One of the primary functions of music is to convey emotion, yet how music accomplishes this task remains unclear. For example, simple correlations between mode (major vs. minor) and emotion (happy vs. sad) do not adequately explain the enormous range, subtlety or complexity of musically induced emotions. In this study, we examined the structural features of unconstrained musical improvisations generated by jazz pianists in response to emotional cues. We hypothesized that musicians would not utilize any universal rules to convey emotions, but would instead combine heterogeneous musical elements together in order to depict positive and negative emotions. Our findings demonstrate a lack of simple correspondence between emotions and musical features of spontaneous musical improvisation. While improvisations in response to positive emotional cues were more likely to be in major keys, have faster tempos, faster key press velocities and more staccato notes when compared to negative improvisations, there was a wide distribution for each emotion with components that directly violated these primary associations. The finding that musicians often combine disparate features together in order to convey emotion during improvisation suggests that structural diversity may be an essential feature of the ability of music to express a wide range of emotion. PMID:25144200

Structure-guided Design and Immunological Characterization of Immunogens Presenting the HIV-1 gp120 V3 Loop on a CTB Scaffold

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

M Totrov; X Jiang; X Kong

2011-12-31

V3 loop is a major neutralizing determinant of the HIV-1 gp120. Using 3D structures of cholera toxin B subunit (CTB), complete V3 in the gp120 context, and V3 bound to a monoclonal antibody (mAb), we designed two V3-scaffold immunogen constructs (V3-CTB). The full-length V3-CTB presenting the complete V3 in a structural context mimicking gp120 was recognized by the large majority of our panel of 24 mAbs. The short V3-CTB presenting a V3 fragment in the conformation observed in the complex with the 447-52D Fab, exhibited high-affinity binding to this mAb. The immunogens were evaluated in rabbits using DNA-prime/protein-boost protocol. Boostingmore » with the full-length V3-CTB induced high anti-V3 titers in sera that potently neutralize multiple HIV virus strains. The short V3-CTB was ineffective. The results suggest that very narrow antigenic profile of an immunogen is associated with poor Ab response. An immunogen with broader antigenic activity elicits robust Ab response.« less

Flow-Mediated Endothelial Mechanotransduction

PubMed Central

Davies, Peter F.

2011-01-01

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed. PMID:7624393

U.S. Nuclear Weapons: Changes in Policy and Force Structure

DTIC Science & Technology

2006-08-10

the Mound Plant , near Dayton OH; the Pinellas Plant , in Clearwater, FL; and the Pantex Plant near Amarillo, TX. These facilities were also operated...major nuclear weapons production facilities. These included the Rocky Flats Plant , outside Denver, CO; the Kansas City Plant , near Kansas City, MO...response to safety concerns. The Rocky Flats Plant , which produced the nuclear triggers, or “pits,” for nuclear weapons closed in 1989, in response

Reclaiming Accountability in Teacher Education

ERIC Educational Resources Information Center

Cochran-Smith, Marilyn; Carney, Molly Cummings; Keefe, Elizabeth Stringer; Burton, Stephani; Chang, Wen-Chia; Fernández, M. Beatriz; Miller, Andrew F.; Sánchez, Juan Gabriel; Baker, Megina

2018-01-01

Teacher accountability has been a major strategy for "fixing" education for the last 2 decades. In this book, Cochran-Smith and her research team argue that it is time for teacher educators to reclaim accountability by adopting a new approach that features intelligent professional responsibility, challenges the structures and processes…

New structural information on food allergens (abstract)

USDA-ARS?s Scientific Manuscript database

A small number of protein families are responsible for food allergies suffered by the majority of allergy patients. What properties of these proteins make them allergens is not clear at present. Reliable methods for allergen prediction and mitigation are lacking. Most the immediate type of food alle...

Disaster Analysis: Police and Fire Departments. Phase 2.

DTIC Science & Technology

1989-03-01

more important conclusions are the following. Fire depart- ments have changed more than police departments in the last decade, taking on new tasks (e.g...than ten officers ( News Journal, 1989:A2). * 13 I! While there is considerable structural variation, the functions or tasks of the various departments...1966), organized responses in major disasters can be differentiated according to whether a new or old structure and a new or old function is manifested

Contrasts in short- and long-term responses of Mediterranean reptile species to fire and habitat structure.

PubMed

Santos, Xavier; Badiane, Arnaud; Matos, Cátia

2016-01-01

Changes in habitat structure constitute a major factor explaining responses of reptiles to fire. However, few studies have examined habitat factors that covary with fire-history variables to explain reptile responses. We hypothesise that more complex habitats should support richer reptile communities, and that species-specific relative abundance should be related to particular habitat features. From spring 2012-2014, twenty-five transects were surveyed in the Albera Region (north-east Iberia). The vegetation structure was measured and the extent of habitat types in a 1000-m buffer around each transect calculated. Reptile-community metrics (species richness and reptile abundance) were related to fire history, vegetation structure, and habitat types, using generalized additive models. These metrics correlated with habitat-structure variables but not with fire history. The number of species increased with more complex habitats but decreased with pine-plantation abundance in the 1000-m buffer. We found contrasting responses among reptiles in terms of time since fire and those responses differed according to vegetation variables and habitat types. An unplanned fire in August 2012 provided the opportunity to compare reptile abundance values between pre-fire and the short term (1-2 years) after the fire. Most species exhibited a negative short-term response to the 2012 fire except Tarentola mauritanica, a gecko that inhabits large rocks, as opposed to other ground-dwelling species. In the reptiles studied, contrasting responses to time since fire are consistent with the habitat-accommodation model of succession. These differences are linked to specific microhabitat preferences and suggest that functional traits can be used to predict species-specific responses to fire.

Variable effects of climate on forest growth in relation to climate extremes, disturbance, and forest dynamics.

PubMed

Itter, Malcolm S; Finley, Andrew O; D'Amato, Anthony W; Foster, Jane R; Bradford, John B

2017-06-01

Changes in the frequency, duration, and severity of climate extremes are forecast to occur under global climate change. The impacts of climate extremes on forest productivity and health remain difficult to predict due to potential interactions with disturbance events and forest dynamics-changes in forest stand composition, density, size and age structure over time. Such interactions may lead to non-linear forest growth responses to climate involving thresholds and lag effects. Understanding how forest dynamics influence growth responses to climate is particularly important given stand structure and composition can be modified through management to increase forest resistance and resilience to climate change. To inform such adaptive management, we develop a hierarchical Bayesian state space model in which climate effects on tree growth are allowed to vary over time and in relation to past climate extremes, disturbance events, and forest dynamics. The model is an important step toward integrating disturbance and forest dynamics into predictions of forest growth responses to climate extremes. We apply the model to a dendrochronology data set from forest stands of varying composition, structure, and development stage in northeastern Minnesota that have experienced extreme climate years and forest tent caterpillar defoliation events. Mean forest growth was most sensitive to water balance variables representing climatic water deficit. Forest growth responses to water deficit were partitioned into responses driven by climatic threshold exceedances and interactions with insect defoliation. Forest growth was both resistant and resilient to climate extremes with the majority of forest growth responses occurring after multiple climatic threshold exceedances across seasons and years. Interactions between climate and disturbance were observed in a subset of years with insect defoliation increasing forest growth sensitivity to water availability. Forest growth was particularly sensitive to climate extremes during periods of high stem density following major regeneration events when average inter-tree competition was high. Results suggest the resistance and resilience of forest growth to climate extremes can be increased through management steps such as thinning to reduce competition during early stages of stand development and small-group selection harvests to maintain forest structures characteristic of older, mature stands. © 2017 by the Ecological Society of America.

Variable effects of climate on forest growth in relation to climate extremes, disturbance, and forest dynamics

USGS Publications Warehouse

Itter, Malcolm S.; Finley, Andrew O.; D'Amato, Anthony W.; Foster, Jane R.; Bradford, John B.

2017-01-01

Changes in the frequency, duration, and severity of climate extremes are forecast to occur under global climate change. The impacts of climate extremes on forest productivity and health remain difficult to predict due to potential interactions with disturbance events and forest dynamics—changes in forest stand composition, density, size and age structure over time. Such interactions may lead to non-linear forest growth responses to climate involving thresholds and lag effects. Understanding how forest dynamics influence growth responses to climate is particularly important given stand structure and composition can be modified through management to increase forest resistance and resilience to climate change. To inform such adaptive management, we develop a hierarchical Bayesian state space model in which climate effects on tree growth are allowed to vary over time and in relation to past climate extremes, disturbance events, and forest dynamics. The model is an important step toward integrating disturbance and forest dynamics into predictions of forest growth responses to climate extremes. We apply the model to a dendrochronology data set from forest stands of varying composition, structure, and development stage in northeastern Minnesota that have experienced extreme climate years and forest tent caterpillar defoliation events. Mean forest growth was most sensitive to water balance variables representing climatic water deficit. Forest growth responses to water deficit were partitioned into responses driven by climatic threshold exceedances and interactions with insect defoliation. Forest growth was both resistant and resilient to climate extremes with the majority of forest growth responses occurring after multiple climatic threshold exceedances across seasons and years. Interactions between climate and disturbance were observed in a subset of years with insect defoliation increasing forest growth sensitivity to water availability. Forest growth was particularly sensitive to climate extremes during periods of high stem density following major regeneration events when average inter-tree competition was high. Results suggest the resistance and resilience of forest growth to climate extremes can be increased through management steps such as thinning to reduce competition during early stages of stand development and small-group selection harvests to maintain forest structures characteristic of older, mature stands.

[Production, specificity and structure of immunoglobulins].

PubMed

Goujard, C; Delfraissy, J F

1991-03-21

Immunoglobulin is a key factor of the immune response resulting from B-cell activation and associated with T-cell stimulation. Because of its structure, this antibody has a dual function: it specifically recognizes the inducer antigen in the variable region and eliminates it by a constant portion which is responsible for effector properties. Surface immunoglobulin, therefore, is the B-cell antigen receptor; it differs from the T-cell receptor in that it recognizes the antigen unbound to the major istocompatibility complex; binding the antigen results in direct signal transduction first in the cytoplasm, then in the nucleus. This receptor can be secreted in the body: it is made up of circulating immunoglobulins. Human immunoglobulins are divided into 5 classes, each of them with its own response kinetics, distribution and functions. The variability of the antibody response accounts for a genetic organization involving numerous genes which may be associated with each other, or mutate, or recombine during maturation of the lymphocytes. Altogether, this system has a theoretical capacity of response to three hundred million different antigens.

Evaluation of passive and active vibration control mechanisms in a microgravity environment

NASA Technical Reports Server (NTRS)

Ellison, J.; Ahmadi, G.; Grodsinsky, C.

1993-01-01

The behavior of equipment and their light secondary attachments in large space structures under orbital excitation is studied. The equipment is modeled as a shear beam and its secondary attachment is treated as a single-degree-of-freedom lumped mass system. Peak responses of the equipment and its secondary system for a variety of vibration control mechanisms are evaluated. A novel active friction control mechanism, by varying the normal force, is suggested. The device uses a magnetic field control to minimize the stick condition, thereby reducing the overall structural response. The results show that the use of the passive vibration control devices could reduce the peak equipment responses to a certain extent. However, major reduction of vibration levels could be achieved only by the use of active devices. Using active control of the interface normal force, the peak responses of the equipment and its attachment are reduced by a factor of 10 over the fixed-base equipment response.

The rising level of medical student debt: potential risk for a national default.

PubMed

Ariyan, S

2000-04-01

At the turn of the 20th century, mostly as a result of the Flexner report, medical education changed dramatically by establishing a scientific basis for the study of medicine within the institutions of the major universities. There have been major and dramatic changes in medicine during the past 80 years that have improved medical education in the United States, but these changes have also placed major economic strains on students who have educational debts. If medicine is a social responsibility to the public, then the public should share the responsibility of identifying and supporting new approaches to funding and financially managing the teaching of future physicians. There is no universal solution because there are various approaches institutions may take to structure these financial responsibilities. This article describes trends in medical student educational debt, identifies the financial needs of medical students, and proposes ways of addressing those needs to avert a possible national financial crisis among medical students. We must invest in medical students because they will be the leaders we need to help care for our society and our own families in the next century.

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

PubMed Central

Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

Reaction Time of a Group of Physics Students

ERIC Educational Resources Information Center

Saxena, Charu; Kaur, Rini; Arun, P.

2008-01-01

The reaction time of a group of students majoring in physics is reported here. Strong correlation between fatigue, reaction time and performance has been observed and may be useful for academicians and administrators responsible for working out timetables, course structures, student counsellings, etc. (Contains 5 figures, 1 table, and 1 footnote.)

Comparative population genomics of Fusarium graminearum reveals adaptive divergence among cereal head blight pathogens

USDA-ARS?s Scientific Manuscript database

In this study we sequenced the genomes of 60 Fusarium graminearum, the major fungal pathogen responsible for Fusarium head blight (FHB) in cereal crops world-wide. To investigate adaptive evolution of FHB pathogens, we performed population-level analyses to characterize genomic structure, signatures...

Effects of pretanning processes on collagen structure and reactivity

USDA-ARS?s Scientific Manuscript database

The cattle hide, a major byproduct of the US meat industry, is the tanner’s substrate, and also the source of collagen for the food and biomaterials industries. Conversion of animal hides into leather is a multistep process that continually evolves in response to economic and environmental concerns...

Genome-wide informative microsatellite database and global population structure of Fusarium virguliforme

USDA-ARS?s Scientific Manuscript database

Sudden death syndrome is one of the leading biotic stresses responsible for soybean yield loss in major soybean production areas. In North America, the disease is caused by the fungus Fusarium virguliforme, while in South America additional Fusarium species cause similar symptoms. Breeding for SDS r...

Towards Mass Higher Education. Issues and Dilemmas.

ERIC Educational Resources Information Center

Organisation for Economic Cooperation and Development, Paris (France).

To discuss a number of major issues related to policies for the future development of higher education systems, the Organisation for Economic Cooperation and Development (OECD) organized a Conference on Future Structures of Post-Secondary Education, which took place in Paris in June 1973. High officials responsible for education policy in OECD…

Inviting other professions to help reduce wildfire property losses

Treesearch

A. Fege; J. Absher

2007-01-01

Preventing structure loss has become a major focal point of wildland firefighting. Most days it feels like wildland fire professionals and land managers are become more and more responsible for reducing property losses in the wildland/urban interface (WUI).What if this impression-and reality-could change?

Revised Guidelines for Comprehensive Health Education, Grades 10-12.

ERIC Educational Resources Information Center

Nebraska State Dept. of Education, Lincoln. Div. of Instructional Services.

These health curriculum guidelines were designed for teachers of secondary students. Four major topic areas are covered: 1) anatomy, physiology, tissues, systems, heredity, physical activity, and nutriition; 2) family structures, functions, and responsibilities; 3) values, stress, and drug abuse; and 4) the environment, disease control, cancer,…

The State Library Agencies; a Survey Project Report, 1975, Second Edition.

ERIC Educational Resources Information Center

Simpson, Donald B., Comp.

The Association of State Library Agencies presents a compilation of data from the 50 state libraries. Information for each state includes name of agency, place in state government organization, powers and duties, purpose and scope of responsibility, organizational structure, personnel, names of key staff, major functional categories, major…

Reliability and risk assessment of structures

NASA Technical Reports Server (NTRS)

Chamis, C. C.

1991-01-01

Development of reliability and risk assessment of structural components and structures is a major activity at Lewis Research Center. It consists of five program elements: (1) probabilistic loads; (2) probabilistic finite element analysis; (3) probabilistic material behavior; (4) assessment of reliability and risk; and (5) probabilistic structural performance evaluation. Recent progress includes: (1) the evaluation of the various uncertainties in terms of cumulative distribution functions for various structural response variables based on known or assumed uncertainties in primitive structural variables; (2) evaluation of the failure probability; (3) reliability and risk-cost assessment; and (4) an outline of an emerging approach for eventual certification of man-rated structures by computational methods. Collectively, the results demonstrate that the structural durability/reliability of man-rated structural components and structures can be effectively evaluated by using formal probabilistic methods.

New metabolic pathway for N,N-dimethyltryptamine

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

Hryhorczuk, L.M.; Rainey, J.M. Jr.; Frohman, C.E.

1986-01-01

N,N-Dimethyltryptamine (DMT) undergoes a major structural alteration when added to whole human blood or its red blood cells in vitro. A new high-pressure liquid chromatography (HPLC) peak is present in extracts of these treated tissues. The compound responsible for this peak has been identified by ultraviolet spectrophotometry and by mass spectrometry as dimethylkynuramine (DMK). The enzyme responsible for this appears to be different from tryptophan 2,3-dioxygenase and also from indoleamine 2,3-dioxygenase.

Citizen Sensors for SHM: Use of Accelerometer Data from Smartphones

PubMed Central

Feng, Maria; Fukuda, Yoshio; Mizuta, Masato; Ozer, Ekin

2015-01-01

Ubiquitous smartphones have created a significant opportunity to form a low-cost wireless Citizen Sensor network and produce big data for monitoring structural integrity and safety under operational and extreme loads. Such data are particularly useful for rapid assessment of structural damage in a large urban setting after a major event such as an earthquake. This study explores the utilization of smartphone accelerometers for measuring structural vibration, from which structural health and post-event damage can be diagnosed. Widely available smartphones are tested under sinusoidal wave excitations with frequencies in the range relevant to civil engineering structures. Large-scale seismic shaking table tests, observing input ground motion and response of a structural model, are carried out to evaluate the accuracy of smartphone accelerometers under operational, white-noise and earthquake excitations of different intensity. Finally, the smartphone accelerometers are tested on a dynamically loaded bridge. The extensive experiments show satisfactory agreements between the reference and smartphone sensor measurements in both time and frequency domains, demonstrating the capability of the smartphone sensors to measure structural responses ranging from low-amplitude ambient vibration to high-amplitude seismic response. Encouraged by the results of this study, the authors are developing a citizen-engaging and data-analytics crowdsourcing platform towards a smartphone-based Citizen Sensor network for structural health monitoring and post-event damage assessment applications. PMID:25643056

Proceedings of the NASA/DOD Control/Structures Interaction Technology Conference (4th) Held in Orlando, Florida on 5-7 November 1990

DTIC Science & Technology

1991-01-15

Orlando, Florida, 5-7 November 1990. The conference was cosponsored by the Wright Laboratory and the NASA Langley Research Center. The Conference...Subiect Terms. Keywords or phrases responsible for writing the report, performing identifying major subjects in the repc.,t. the research , or...Laboratory and the NASA Langley Research Center have agreed to sponsor alternately a series of annual control/structures interaction technology

Homogalacturonan-modifying enzymes: structure, expression, and roles in plants

PubMed Central

Sénéchal, Fabien; Wattier, Christopher; Rustérucci, Christine; Pelloux, Jérôme

2014-01-01

Understanding the changes affecting the plant cell wall is a key element in addressing its functional role in plant growth and in the response to stress. Pectins, which are the main constituents of the primary cell wall in dicot species, play a central role in the control of cellular adhesion and thereby of the rheological properties of the wall. This is likely to be a major determinant of plant growth. How the discrete changes in pectin structure are mediated is thus a key issue in our understanding of plant development and plant responses to changes in the environment. In particular, understanding the remodelling of homogalacturonan (HG), the most abundant pectic polymer, by specific enzymes is a current challenge in addressing its fundamental role. HG, a polymer that can be methylesterified or acetylated, can be modified by HGMEs (HG-modifying enzymes) which all belong to large multigenic families in all species sequenced to date. In particular, both the degrees of substitution (methylesterification and/or acetylation) and polymerization can be controlled by specific enzymes such as pectin methylesterases (PMEs), pectin acetylesterases (PAEs), polygalacturonases (PGs), or pectate lyases-like (PLLs). Major advances in the biochemical and functional characterization of these enzymes have been made over the last 10 years. This review aims to provide a comprehensive, up to date summary of the recent data concerning the structure, regulation, and function of these fascinating enzymes in plant development and in response to biotic stresses. PMID:25056773

Mid-frequency Band Dynamics of Large Space Structures

NASA Technical Reports Server (NTRS)

Coppolino, Robert N.; Adams, Douglas S.

2004-01-01

High and low intensity dynamic environments experienced by a spacecraft during launch and on-orbit operations, respectively, induce structural loads and motions, which are difficult to reliably predict. Structural dynamics in low- and mid-frequency bands are sensitive to component interface uncertainty and non-linearity as evidenced in laboratory testing and flight operations. Analytical tools for prediction of linear system response are not necessarily adequate for reliable prediction of mid-frequency band dynamics and analysis of measured laboratory and flight data. A new MATLAB toolbox, designed to address the key challenges of mid-frequency band dynamics, is introduced in this paper. Finite-element models of major subassemblies are defined following rational frequency-wavelength guidelines. For computational efficiency, these subassemblies are described as linear, component mode models. The complete structural system model is composed of component mode subassemblies and linear or non-linear joint descriptions. Computation and display of structural dynamic responses are accomplished employing well-established, stable numerical methods, modern signal processing procedures and descriptive graphical tools. Parametric sensitivity and Monte-Carlo based system identification tools are used to reconcile models with experimental data and investigate the effects of uncertainties. Models and dynamic responses are exported for employment in applications, such as detailed structural integrity and mechanical-optical-control performance analyses.

Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell.

PubMed

Arrigo, André-Patrick

2017-07-01

Constitutively expressed small heat shock protein HspB1 regulates many fundamental cellular processes and plays major roles in many human pathological diseases. In that regard, this chaperone has a huge number of apparently unrelated functions that appear linked to its ability to recognize many client polypeptides that are subsequently modified in their activity and/or half-life. A major parameter to understand how HspB1 is dedicated to interact with particular clients in defined cellular conditions relates to its complex oligomerization and phosphorylation properties. Indeed, HspB1 structural organization displays dynamic and complex rearrangements in response to changes in the cellular environment or when the cell physiology is modified. These structural modifications probably reflect the formation of structural platforms aimed at recognizing specific client polypeptides. Here, I have reviewed data from the literature and re-analyzed my own studies to describe and discuss these fascinating changes in HspB1 structural organization.

A Simple Model Framework to Explore the Deeply Uncertain, Local Sea Level Response to Climate Change. A Case Study on New Orleans, Louisiana

NASA Astrophysics Data System (ADS)

Bakker, Alexander; Louchard, Domitille; Keller, Klaus

2016-04-01

Sea-level rise threatens many coastal areas around the world. The integrated assessment of potential adaptation and mitigation strategies requires a sound understanding of the upper tails and the major drivers of the uncertainties. Global warming causes sea-level to rise, primarily due to thermal expansion of the oceans and mass loss of the major ice sheets, smaller ice caps and glaciers. These components show distinctly different responses to temperature changes with respect to response time, threshold behavior, and local fingerprints. Projections of these different components are deeply uncertain. Projected uncertainty ranges strongly depend on (necessary) pragmatic choices and assumptions; e.g. on the applied climate scenarios, which processes to include and how to parameterize them, and on error structure of the observations. Competing assumptions are very hard to objectively weigh. Hence, uncertainties of sea-level response are hard to grasp in a single distribution function. The deep uncertainty can be better understood by making clear the key assumptions. Here we demonstrate this approach using a relatively simple model framework. We present a mechanistically motivated, but simple model framework that is intended to efficiently explore the deeply uncertain sea-level response to anthropogenic climate change. The model consists of 'building blocks' that represent the major components of sea-level response and its uncertainties, including threshold behavior. The framework's simplicity enables the simulation of large ensembles allowing for an efficient exploration of parameter uncertainty and for the simulation of multiple combined adaptation and mitigation strategies. The model framework can skilfully reproduce earlier major sea level assessments, but due to the modular setup it can also be easily utilized to explore high-end scenarios and the effect of competing assumptions and parameterizations.

Differential Transmembrane Domain GXXXG Motif Pairing Impacts Major Histocompatibility Complex (MHC) Class II Structure*

PubMed Central

Dixon, Ann M.; Drake, Lisa; Hughes, Kelly T.; Sargent, Elizabeth; Hunt, Danielle; Harton, Jonathan A.; Drake, James R.

2014-01-01

Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II αβ heterodimer in determining molecular structure and function. Our previous studies identified an MHC class II conformer that is marked by the Ia.2 epitope. These Ia.2+ class II conformers are lipid raft-associated and able to drive both tyrosine kinase signaling and efficient antigen presentation to CD4 T cells. Here, we establish that the Ia.2+ I-Ak conformer is formed early in the class II biosynthetic pathway and that differential pairing of highly conserved transmembrane domain GXXXG dimerization motifs is responsible for formation of Ia.2+ versus Ia.2− I-Ak class II conformers and controlling lipid raft partitioning. These findings provide a molecular explanation for the formation of two distinct MHC class II conformers that differ in their inherent ability to signal and drive robust T cell activation, providing new insight into the role of MHC class II in regulating antigen-presenting cell-T cell interactions critical to the initiation and control of multiple aspects of the immune response. PMID:24619409

Factor Structure and Reliability of the 2008 and 2009 SERU/UCUES Questionnaire Core. SERU Project Technical Report

ERIC Educational Resources Information Center

Chatman, Steve

2009-01-01

This technical report summarizes the third independent factor analysis of the SERU/UCUES questionnaire responses of students with majors. The 2009 solution employed the same quantitative analysis used in the prior solutions--varimax orthogonal rotation to determine principal components followed by promax oblique rotation to identify…

Young People in Britain at the Beginning of a New Century.

ERIC Educational Resources Information Center

Coleman, John

2000-01-01

Considers major social changes that have affected adolescent development in the latter part of the twentieth century, including changes in the labor market, family structure, attitudes toward race and gender, sexuality, mental health, and social exclusion. Suggests ways the behavior and development of young people will change in response. (JPB)

Higher Education in Texas: Student Aid and Governance. Working Paper.

ERIC Educational Resources Information Center

Tolo, Kenneth W.

Current issues facing higher education in Texas are examined with an emphasis on student financial aid programs and governance. The formal organizational structure and the responsibilities of the major governmental units are described, and the role played by state government in higher education through its tuition policies and its student aid…

78 FR 45781 - Accreditation of Third-Party Auditors/Certification Bodies to Conduct Food Safety Audits and to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... following major elements: (1) Legal responsibility, structure, and impartiality; (2) management systems... contains similar requirements for bodies auditing management systems: (1) Legal matters and contractual... 72,611,521 74,396,099 Table of Contents I. Introduction II. Background A. Legal Authority B. FDA...

Major Losses

ERIC Educational Resources Information Center

Kravis, Miles

2009-01-01

From 2003 to 2005, fires on school properties cost about $85 million a year. An estimated 14,700 fires required a fire department response: 36 percent were trash fires, 19 percent were fires in open fields, and 43 percent were structural fires. Sometimes, the needs of school security seem to conflict with the requirements of fire safety. In this…

Safe sedation practices among gastroenterology registrars: do we need more training?

PubMed Central

Mohanaruban, Aruchuna; Bryce, Kathleen; Radhakrishnan, Archchana; Gallaher, Joseph; Johnson, Gavin

2015-01-01

Endoscopy training is a central component of gastroenterology training for the vast majority of UK trainees, and integral to this is the practice of safe sedation. The majority of endoscopic procedures are performed with the patient under conscious sedation with a benzodiazepine, often combined with an opioid. Little data exists on the practice of sedation among gastroenterology trainees, including their degree of knowledge of the common sedation agents used and their actions. Using both an online and paper-based questionnaire, we surveyed current gastroenterology speciality trainees (ST) in the UK and received 78 responses giving a response rate of 10%. Fifty-one per cent of the trainees did not receive structured training in safe sedation, despite national guidelines advising this to be an essential part of the training programme, and 92% felt a structured sedation course would be beneficial. We also identified some gaps in trainees’ knowledge of the action of sedation agents. We propose that a formal training session in sedation or an e-learning module could be incorporated as part of a deanery or trust induction for gastroenterology trainees and kept under regular review. PMID:28839813

Complement factor H in host defense and immune evasion.

PubMed

Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

2017-05-01

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

An approximate methods approach to probabilistic structural analysis

NASA Technical Reports Server (NTRS)

Mcclung, R. C.; Millwater, H. R.; Wu, Y.-T.; Thacker, B. H.; Burnside, O. H.

1989-01-01

A probabilistic structural analysis method (PSAM) is described which makes an approximate calculation of the structural response of a system, including the associated probabilistic distributions, with minimal computation time and cost, based on a simplified representation of the geometry, loads, and material. The method employs the fast probability integration (FPI) algorithm of Wu and Wirsching. Typical solution strategies are illustrated by formulations for a representative critical component chosen from the Space Shuttle Main Engine (SSME) as part of a major NASA-sponsored program on PSAM. Typical results are presented to demonstrate the role of the methodology in engineering design and analysis.

Lean Middleware

NASA Technical Reports Server (NTRS)

Maluf, David A.; Bell, David g.; Ashish, Naveen

2005-01-01

This paper describes an approach to achieving data integration across multiple sources in an enterprise, in a manner that is cost efficient and economically scalable. We present an approach that does not rely on major investment in structured, heavy-weight database systems for data storage or heavy-weight middleware responsible for integrated access. The approach is centered around pushing any required data structure and semantics functionality (schema) to application clients, as well as pushing integration specification and functionality to clients where integration can be performed on-the-fly .

Molecular dynamics simulations suggest changes in electrostatic interactions as a potential mechanism through which serine phosphorylation inhibits DNA Polymerase β's activity.

PubMed

Homouz, Dirar; Joyce-Tan, Kwee Hong; Shahir Shamsir, Mohd; Moustafa, Ibrahim M; Idriss, Haitham

2018-01-01

DNA polymerase β is a 39kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31kDa domain responsible for the polymerase activity and an 8kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics. The simulations show drastic conformational changes of the polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced conformational changes transform the closed (active) enzyme structure into an open one. Further analysis of the results points to a key hydrogen bond and newly formed salt bridges as potential drivers of these structural fluctuations. The changes observed with S44/55 and S55 phosphorylation were less dramatic than S44 and the integrity of the H-bond was not compromised. Thus the phosphorylation of S44 is likely the major contributor to structural fluctuations that lead to loss of enzymatic activity. Copyright © 2017. Published by Elsevier Inc.

An aeroelastician's perspective of wind tunnel and flight experiences with active control of structural response and stability

NASA Technical Reports Server (NTRS)

Hanson, P. W.

1984-01-01

Active controls technology is assessed based on a review of most of the wind-tunnel and flight tests and actual applications of active control concepts since the late sixties. The distinction is made between so-called ""rigid-body'' active control functions and those that involve significant modification of structural elastic response or stability. Both areas are reviewed although the focus is on the latter area. The basic goals and major results of the various studies or applications are summarized, and the anticipated use of active controls on current and near-future research and demonstration aircraft is discussed. Some of the ""holes'' remaining in the feasbility/benefits demonstration of active controls technology are examined.

Dynamic analysis of the large deployable reflector

NASA Technical Reports Server (NTRS)

Calleson, Robert E.; Scott, A. Don

1987-01-01

The Large Deployable Reflector (LDR) is to be an astronomical observatory orbiting above Earth's obscuring atmosphere and operating in the spectral range between 30 microns and 1000 microns wavelength. The LDR will be used to study such astronomical phenomena as stellar and galactic formation, cosmology, and planetary atmospheres. The LDR will be the first observatory to be erected and assembled in space. This distinction brings with it several major technological challenges such as the development of ultra-lightweight deployable mirrors, advanced mirror fabrication techniques, advanced structures, and control of vibrations due to various sources of excitation. The purpose of this analysis is to provide an assessment of the vibrational response due to secondary mirror chopping and LDR slewing. The dynamic response of two 20-m LDR configurations was studied. Two mirror support configurations were investigated for the Ames concept, the first employs a six-strut secondary mirror support structure, while the second uses a triple-bipod support design. All three configurations were modeled using a tetrahedral truss design for the primary mirror support structure. Response resulting from secondary mirror chopping was obtained for the two Ames configurations, and the response of the primary mirror from slewing was obtained for all three configurations.

Role of various hormones in photosynthetic responses of green plants under environmental stresses.

PubMed

Poonam; Bhardwaj, Renu; Kaur, Ravdeep; Bali, Shagun; Kaur, Parminder; Sirhindi, Geetika; Thukral, Ashwani K; Ohri, Puja; Vig, Adarsh P

2015-01-01

Environmental stress includes adverse factors like water deficit, high salinity, enhanced temperature and heavy metals etc. These stresses alter the normal growth and metabolic processes of plants including photosynthesis. Major photosynthetic responses under various stresses include inhibition of photosystems (I and II), changes in thylakoid complexes, decreased photosynthetic activity and modifications in structure and functions of chloroplasts etc. Various defense mechanisms are triggered inside the plants in response to these stresses that are regulated by plant hormones or plant growth regulators. These phytohormones include abscisic acid, auxins, cytokinins, ethylene, brassinosteroids, jasmonates and salicylic acid etc. The present review focuses on stress protective effects of plants hormones on the photosynthetic responses.

An optimal design of wind turbine and ship structure based on neuro-response surface method

NASA Astrophysics Data System (ADS)

Lee, Jae-Chul; Shin, Sung-Chul; Kim, Soo-Young

2015-07-01

The geometry of engineering systems affects their performances. For this reason, the shape of engineering systems needs to be optimized in the initial design stage. However, engineering system design problems consist of multi-objective optimization and the performance analysis using commercial code or numerical analysis is generally time-consuming. To solve these problems, many engineers perform the optimization using the approximation model (response surface). The Response Surface Method (RSM) is generally used to predict the system performance in engineering research field, but RSM presents some prediction errors for highly nonlinear systems. The major objective of this research is to establish an optimal design method for multi-objective problems and confirm its applicability. The proposed process is composed of three parts: definition of geometry, generation of response surface, and optimization process. To reduce the time for performance analysis and minimize the prediction errors, the approximation model is generated using the Backpropagation Artificial Neural Network (BPANN) which is considered as Neuro-Response Surface Method (NRSM). The optimization is done for the generated response surface by non-dominated sorting genetic algorithm-II (NSGA-II). Through case studies of marine system and ship structure (substructure of floating offshore wind turbine considering hydrodynamics performances and bulk carrier bottom stiffened panels considering structure performance), we have confirmed the applicability of the proposed method for multi-objective side constraint optimization problems.

Preliminary analysis of murine cytotoxic T cell responses to the proteins of the flavivirus Kunjin using vaccinia virus expression.

PubMed

Parrish, C R; Coia, G; Hill, A; Müllbacher, A; Westaway, E G; Blanden, R V

1991-07-01

A series of recombinant vaccinia viruses expressing various parts of the entire Kunjin virus (KUN) coding region was used to analyse the cytotoxic T (Tc) cell responses to KUN. CBA/H mice inoculated with KUN or West Nile virus were shown to develop responses to KUN or various vaccinia virus expression constructs in either primary cytotoxic assays, or after secondary stimulation of the Tc cells in vitro with KUN antigens. Tc cells from CBA mice showed the strongest response to target cells infected with recombinant vaccinia viruses expressing parts of the KUN NS3 and NS4A proteins, and only a weak response to the other structural or non-structural proteins. Further analysis of deleted versions of the NS3-NS4A region showed that the main epitope recognized was derived from a sequence of 99 amino acids spanning parts of NS3 and NS4A. No other major epitopes were detected by Tc cells from CBA mice in the remaining 3333 amino acids of the KUN polypeptide.

Random lattice structures. Modelling, manufacture and FEA of their mechanical response

NASA Astrophysics Data System (ADS)

Maliaris, G.; Sarafis, I. T.; Lazaridis, T.; Varoutoglou, A.; Tsakataras, G.

2016-11-01

The implementation of lightweight structures in various applications, especially in Aerospace/ Automotive industries and Orthopaedics, has become a necessity due to their exceptional mechanical properties with respect to reduced weight. In this work we present a Voronoi tessellation based algorithm, which has been developed for modelling stochastic lattice structures. With the proposed algorithm, is possible to generate CAD geometry with controllable structural parameters, such as porosity, cell number and strut thickness. The digital structures were transformed into physical objects through the combination of 3D printing technics and investment casting. This process was applied to check the mechanical behaviour of generated digital models. Until now, the only way to materialize such structures into physical objects, was feasible through 3D printing methods such as Selective Laser Sintering/ Melting (SLS/ SLM). Investment casting possesses numerous advantages against SLS or SLA, with the major one being the material variety. On the other hand, several trials are required in order to calibrate the process parameters to have successful castings, which is the major drawback of investment casting. The manufactured specimens were subjected to compression tests, where their mechanical response was registered in the form of compressive load - displacement curves. Also, a finite element model was developed, using the specimens’ CAD data and compression test parameters. The FE assisted calculation of specimen plastic deformation is identical with the one of the physical object, which validates the conclusions drawn from the simulation results. As it was observed, strut contact is initiated when specimen deformation is approximately 5mm. Although FE calculated compressive force follows the same trend for the first 3mm of compression, then diverges because of the elasto-plastic FE model type definition and the occurred remeshing steps.

Characterization of molecular structural changes in pectin during juice cloud destabilization in frozen concentrated orange juice

USDA-ARS?s Scientific Manuscript database

Pectin comprises one of the major components of cloud material in citrus juices. Juice cloud is a complex mixture of polysaccharides, proteins and lower molecular weight compounds that are responsible for the turbid appearance of citrus juices. The stability of juice cloud depends on a number of fac...

Non-arborescent vegetation trajectories following repeated hurricane disturbance: ephemeral versus enduring responses

Treesearch

Alejandro A. Royo; Tamara Heartsill-Scalley; Samuel Moya; Fred N. Scatena

2011-01-01

Hurricanes strongly influence short-term patterns of plant community structure, composition, and abundance and are a major contributor to the maintenance of plant diversity in many forests. Although much research has focused on the immediate and long-term effects of hurricane disturbance on tree diversity, far less attention has been devoted to the non-arborescent...

The Changing Landscape--State Policy-Making: Public Service and Teacher Education in Ireland 1950-1980

ERIC Educational Resources Information Center

Herron, Donald; Harford, Judith

2016-01-01

Radical economic policy change from the 1950s had major implications for Irish education which had traditionally drawn its values and orientation from Catholicism and cultural nationalism. While change to the economically-related administrative structures were bold and innovative, responses in the sphere of education were less so. This article…

Beginning School Math Competence: Minority and Majority Comparisons. Report No. 34.

ERIC Educational Resources Information Center

Entwisle, Doris R.; Alexander, Karl L.

This paper uses a structural model with a large random sample of urban children to explain children's competence in math concepts and computation at the time they begin first grade. These two aspects of math ability respond differently to environmental resources, with math concepts much more responsive to family factors before formal schooling…

The Federal Civil Rights Enforcement Effort--1974. Volume 5: To Eliminate Employment Discrimination.

ERIC Educational Resources Information Center

Adams, Whitney; And Others

This report evaluates the Civil Rights activities of four federal agencies considered to have major responsibilities for ensuring equal employment opportunity. It is the fifth of a series of seven reports to be issued by the U.S. Commission on Civil Rights describing the structure, mechanisms, and procedures used by the federal departments and…

LIST/BMI Turbines Instrumentation and Infrastructure

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

JONES,PERRY L.; SUTHERLAND,HERBERT J.; NEAL,BYRON A.

2001-06-01

In support of two major SNL programs, the Long-term Inflow and Structural Test (LIST) program and the Blade Manufacturing Initiative (BMI), three Micon 65/13M wind turbines have been erected at the USDA Agriculture Research Service (ARS) center in Bushland, Texas. The inflow and structural response of these turbines are being monitored with an array of 60 instruments: 34 to characterize the inflow, 19 to characterize structural response and 7 to characterize the time-varying state of the turbine. The primary characterization of the inflow into the LIST turbine relies upon an array of five sonic anemometers. Primary characterization of the structuralmore » response of the turbine uses several sets of strain gauges to measure bending loads on the blades and the tower and two accelerometers to measure the motion of the nacelle. Data are sampled at a rate of 30 Hz using a newly developed data acquisition system. The system features a time-synchronized continuous data stream and telemetered data from the turbine rotor. This paper documents the instruments and infrastructure that have been developed to monitor these turbines and their inflow.« less

Crystal structure of the Leishmania major peroxidase–cytochrome c complex

PubMed Central

Jasion, Victoria S.; Doukov, Tzanko; Pineda, Stephanie H.; Li, Huiying; Poulos, Thomas L.

2012-01-01

The causative agent of leishmaniasis is the protozoan parasite Leishmania major. Part of the host protective mechanism is the production of reactive oxygen species including hydrogen peroxide. In response, L. major produces a peroxidase, L. major peroxidase (LmP), that helps to protect the parasite from oxidative stress. LmP is a heme peroxidase that catalyzes the peroxidation of mitochondrial cytochrome c. We have determined the crystal structure of LmP in a complex with its substrate, L. major cytochrome c (LmCytc) to 1.84 Å, and compared the structure to its close homolog, the yeast cytochrome c peroxidase–cytochrome c complex. The binding interface between LmP and LmCytc has one strong and one weak ionic interaction that the yeast system lacks. The differences between the steady-state kinetics correlate well with the Lm redox pair being more dependent on ionic interactions, whereas the yeast redox pair depends more on nonpolar interactions. Mutagenesis studies confirm that the ion pairs at the intermolecular interface are important to both kcat and KM. Despite these differences, the electron transfer path, with respect to the distance between hemes, along the polypeptide chain is exactly the same in both redox systems. A potentially important difference, however, is the side chains involved. LmP has more polar groups (Asp and His) along the pathway compared with the nonpolar groups (Leu and Ala) in the yeast system, and as a result, the electrostatic environment along the presumed electron transfer path is substantially different. PMID:23100535

Structural Health Management of Damaged Aircraft Structures Using the Digital Twin Concept

NASA Technical Reports Server (NTRS)

Seshadri, Banavara R.; Krishnamurthy, Thiagarajan

2017-01-01

The development of multidisciplinary integrated Structural Health Management (SHM) tools will enable accurate detection, and prognosis of damaged aircraft under normal and adverse conditions during flight. As part of the digital twin concept, methodologies are developed by using integrated multiphysics models, sensor information and input data from an in-service vehicle to mirror and predict the life of its corresponding physical twin. SHM tools are necessary for both damage diagnostics and prognostics for continued safe operation of damaged aircraft structures. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable, catastrophic propagation of damage during a flight, load levels must be maintained that are below a reduced load-carrying capacity for continued safe operation of an aircraft. Hence, a capability is needed for accurate real-time predictions of damage size and safe load carrying capacity for structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size, location, and orientation is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size, location, and orientation is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries, and sizes.

Coordinating management disciplines to build operational resilience in response to a major crisis situation.

PubMed

Drachal, Marcin

2017-01-01

Using case studies of the Ebola outbreak in Western Africa in 2014, and the terrorist attacks in Paris and Brussels in 2015 and 2016 respectively, this paper demonstrates how various resilience-related corporate functions contributed to effective crisis response. This paper describes the logical order of actions taken in each of the cases, and how the organisation prioritised its assets and coordinated activities to ensure the response was adequate, efficient and timely. The article demonstrates how business continuity, physical security, threat management, security intelligence and incident management worked together to support the organisation's crisis management structures in complex crisis situations.

Design and Development of Microsomal Prostaglandin E2 Synthase-1 Inhibitors: Challenges and Future Directions.

PubMed

Koeberle, Andreas; Laufer, Stefan A; Werz, Oliver

2016-07-14

Microsomal prostaglandin E2 synthase (mPGES)-1 is responsible for the massive prostaglandin E2 (PGE2) formation during inflammation. Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal anti-inflammatory drugs. The first selective mPGES-1 inhibitors recently entered clinical trials. Major challenges for drug development have been the high plasma protein binding of lead structures, interspecies discrepancies, nuisance inhibition, sophisticated enzyme assays, and limited structural information about the mPGES-1 inhibitor binding site. Since most of these drawbacks could be solved during the past few years, we are standing at the threshold of a new era of mPGES-1-targeting anti-inflammatory drugs. This perspective introduces mPGES-1 as a key player within the network of eicosanoid biosynthesis and summarizes our current understanding of its structure and mechanism. Moreover, we present high-throughput and in silico screening techniques and discuss the structure-activity relationship and pharmacological potential of major mPGES-1 inhibitor classes in light of recent insights from pharmacophore models and cocrystallization studies.

Synthesis of structurally diverse major groove DNA interstrand crosslinks using three different aldehyde precursors

PubMed Central

Mukherjee, Shivam; Guainazzi, Angelo; Schärer, Orlando D.

2014-01-01

DNA interstrand crosslinks (ICLs) are extremely cytotoxic lesions that block essential cellular processes, such as replication and transcription. Crosslinking agents are widely used in cancer chemotherapy and form an array of structurally diverse ICLs. Despite the clinical success of these agents, resistance of tumors to crosslinking agents, for example, through repair of these lesions by the cellular machinery remains a problem. We have previously reported the synthesis of site-specific ICLs mimicking those formed by nitrogen mustards to facilitate the studies of cellular responses to ICL formation. Here we extend these efforts and report the synthesis of structurally diverse major groove ICLs that induce severe, little or no distortion in the DNA. Our approach employs the incorporation of aldehyde precursors of different lengths into complementary strands and ICL formation using a double reductive amination with a variety of amines. Our studies provide insight into the structure and reactivity parameters of ICL formation by double reductive amination and yield a set of diverse ICLs that will be invaluable for exploring structure–activity relationships in ICL repair. PMID:24782532

The Role of CMR in Cardiomyopathies

PubMed Central

Kramer, Christopher M.

2015-01-01

Cardiac magnetic resonance imaging (CMR) has made major inroads in the new millenium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. An emerging major role for CMR in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes. PMID:26033902

New Tool Released for Engine-Airframe Blade-Out Structural Simulations

NASA Technical Reports Server (NTRS)

Lawrence, Charles

2004-01-01

Researchers at the NASA Glenn Research Center have enhanced a general-purpose finite element code, NASTRAN, for engine-airframe structural simulations during steady-state and transient operating conditions. For steady-state simulations, the code can predict critical operating speeds, natural modes of vibration, and forced response (e.g., cabin noise and component fatigue). The code can be used to perform static analysis to predict engine-airframe response and component stresses due to maneuver loads. For transient response, the simulation code can be used to predict response due to bladeoff events and subsequent engine shutdown and windmilling conditions. In addition, the code can be used as a pretest analysis tool to predict the results of the bladeout test required for FAA certification of new and derivative aircraft engines. Before the present analysis code was developed, all the major aircraft engine and airframe manufacturers in the United States and overseas were performing similar types of analyses to ensure the structural integrity of engine-airframe systems. Although there were many similarities among the analysis procedures, each manufacturer was developing and maintaining its own structural analysis capabilities independently. This situation led to high software development and maintenance costs, complications with manufacturers exchanging models and results, and limitations in predicting the structural response to the desired degree of accuracy. An industry-NASA team was formed to overcome these problems by developing a common analysis tool that would satisfy all the structural analysis needs of the industry and that would be available and supported by a commercial software vendor so that the team members would be relieved of maintenance and development responsibilities. Input from all the team members was used to ensure that everyone's requirements were satisfied and that the best technology was incorporated into the code. Furthermore, because the code would be distributed by a commercial software vendor, it would be more readily available to engine and airframe manufacturers, as well as to nonaircraft companies that did not previously have access to this capability.

Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution

PubMed Central

Paget, Mark S.

2015-01-01

Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2–4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor. PMID:26131973

NASA Lewis Research Center Workshop on Forced Response in Turbomachinery

NASA Technical Reports Server (NTRS)

Stefko, George L. (Compiler); Murthy, Durbha V. (Compiler); Morel, Michael (Compiler); Hoyniak, Dan (Compiler); Gauntner, Jim W. (Compiler)

1994-01-01

A summary of the NASA Lewis Research Center (LeRC) Workshop on Forced Response in Turbomachinery in August, 1993 is presented. It was sponsored by the following NASA organizations: Structures, Space Propulsion Technology, and Propulsion Systems Divisions of NASA LeRC and the Aeronautics and Advanced Concepts & Technology Offices of NASA Headquarters. In addition, the workshop was held in conjunction with the GUIde (Government/Industry/Universities) Consortium on Forced Response. The workshop was specifically designed to receive suggestions and comments from industry on current research at NASA LeRC in the area of forced vibratory response of turbomachinery blades which includes both computational and experimental approaches. There were eight presentations and a code demonstration. Major areas of research included aeroelastic response, steady and unsteady fluid dynamics, mistuning, and corresponding experimental work.

PRSEUS Pressure Cube Test Data and Response

NASA Technical Reports Server (NTRS)

Lovejoy, Andrew E.

2013-01-01

NASA s Environmentally Responsible Aviation (ERA) Program is examining the hybrid wing body (HWB) aircraft, among others, in an effort to increase the fuel efficiency of commercial aircraft. The HWB design combines features of a flying wing with features of conventional transport aircraft, and has the advantage of simultaneously increasing both fuel efficiency and payload. Recent years have seen an increased focus on the structural performance of the HWB. The key structural challenge of a HWB airframe is the ability to create a cost and weight efficient, non-circular, pressurized shell. Conventional round fuselage sections react cabin pressure by hoop tension. However, the structural configuration of the HWB subjects the majority of the structural panels to bi-axial, in-plane loads in addition to the internal cabin pressure, which requires more thorough examination and analysis than conventional transport aircraft components having traditional and less complex load paths. To address this issue, while keeping structural weights low, extensive use of advanced composite materials is made. This report presents the test data and preliminary conclusions for a pressurized cube test article that utilizes Boeing's Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS), and which is part of the building block approach used for HWB development.

Implementation and extension of the impulse transfer function method for future application to the space shuttle project. Volume 2: Program description and user's guide

NASA Technical Reports Server (NTRS)

Patterson, G.

1973-01-01

The data processing procedures and the computer programs were developed to predict structural responses using the Impulse Transfer Function (ITF) method. There are three major steps in the process: (1) analog-to-digital (A-D) conversion of the test data to produce Phase I digital tapes (2) processing of the Phase I digital tapes to extract ITF's and storing them in a permanent data bank, and (3) predicting structural responses to a set of applied loads. The analog to digital conversion is performed by a standard package which will be described later in terms of the contents of the resulting Phase I digital tape. Two separate computer programs have been developed to perform the digital processing.

Worldwide variation in within-canopy photosynthetic acclimation: differences in temporal and environmental controls among plant functional types

NASA Astrophysics Data System (ADS)

Niinemets, Ülo; Keenan, Trevor

2017-04-01

Major light gradients, characteristically 10- to 50-fold, constitute the most prominent feature of plant canopies. These gradients drive within-canopy variation in foliage structural, chemical and physiological traits. As a key acclimation response to variation in light availability, foliage photosynthetic capacity per area (Aarea) increases with increasing light availability within the canopy, maximizing whole canopy photosynthesis. Recently, a worldwide database including 831 within-canopy gradients with standardized light estimates for 304 species belonging to major vascular plant functional types was constructed and within-canopy variation in photosynthetic acclimation was characterized (Niinemets Ü, Keenan TF, Hallik L (2015) Tansley review. A worldwide analysis of within-canopy variations in leaf structural, chemical and physiological traits across plant functional types. The New Phytologist 205: 973-993). However, the understanding of how within-canopy photosynthetic gradients vary during the growing season and in response to site and stand characteristics is still limited. Here we analyzed temporal, environmental and site (nutrient availability, stand density, ambient CO2 concentration, water availability) sources of variation in within-canopy photosynthetic acclimation in different plant functional types. Variation in key structural (leaf dry mass per unit area, MA), chemical (nitrogen content per dry mass, NM, and area, NA) and physiological (photosynthetic nitrogen use efficiency, EN) photosynthetic capacity per dry mass, Amass and area, Aarea) was examined. The analysis demonstrates major, typically 1.5-2-fold, time-, environment and site-dependent modifications in within-canopy variation in foliage photosynthetic capacity. However, the magnitude and direction of temporal and environmental variations in plasticity significantly varied among functional types. Species with longer leaf life span and low rates of canopy expansion or flush-type canopy formation had lower within canopy plasticity during the growing season and in response to environmental and site modifications than species with high rates of canopy expansion and leaf turnover. The fast canopy-expanding species that grow in highly dynamic light environments, actively modified Aarea by nitrogen reallocation among and partitioning within leaves. In contrast, species with low rate of leaf turnover generally exhibited a passive acclimation response with variation in Aarea primarily determined by light-dependent modifications in leaf structure during leaf growth. Due to limited reacclimation capacity in species with low leaf turnover, within-canopy variation in Aarea decreased with increasing leaf age in these species. Furthermore, the plasticity responded less to modifications in environmental and site characteristics than in species with faster leaf turnover. This analysis concludes that the rate of leaf turnover is the key trait determining the temporal variation and environmental responses of canopy photosynthetic acclimation.

Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

Photo-responsive polymeric micelles.

PubMed

Huang, Yu; Dong, Ruijiao; Zhu, Xinyuan; Yan, Deyue

2014-09-07

Photo-responsive polymeric micelles have received increasing attention in both academic and industrial fields due to their efficient photo-sensitive nature and unique nanostructure. In view of the photo-reaction mechanism, photo-responsive polymeric micelles can be divided into five major types: (1) photoisomerization polymeric micelles, (2) photo-induced rearrangement polymeric micelles, (3) photocleavage polymeric micelles, (4) photo-induced crosslinkable polymeric micelles, and (5) photo-induced energy conversion polymeric micelles. This review highlights the recent advances of photo-responsive polymeric micelles, including the design, synthesis and applications in various biomedical fields. Especially, the influence of different photo-reaction mechanisms on the morphology, structure and properties of the polymeric micelles is emphasized. Finally, the possible future directions and perspectives in this emerging area are briefly discussed.

On the dimension of complex responses in nonlinear structural vibrations

NASA Astrophysics Data System (ADS)

Wiebe, R.; Spottswood, S. M.

2016-07-01

The ability to accurately model engineering systems under extreme dynamic loads would prove a major breakthrough in many aspects of aerospace, mechanical, and civil engineering. Extreme loads frequently induce both nonlinearities and coupling which increase the complexity of the response and the computational cost of finite element models. Dimension reduction has recently gained traction and promises the ability to distill dynamic responses down to a minimal dimension without sacrificing accuracy. In this context, the dimensionality of a response is related to the number of modes needed in a reduced order model to accurately simulate the response. Thus, an important step is characterizing the dimensionality of complex nonlinear responses of structures. In this work, the dimensionality of the nonlinear response of a post-buckled beam is investigated. Significant detail is dedicated to carefully introducing the experiment, the verification of a finite element model, and the dimensionality estimation algorithm as it is hoped that this system may help serve as a benchmark test case. It is shown that with minor modifications, the method of false nearest neighbors can quantitatively distinguish between the response dimension of various snap-through, non-snap-through, random, and deterministic loads. The state-space dimension of the nonlinear system in question increased from 2-to-10 as the system response moved from simple, low-level harmonic to chaotic snap-through. Beyond the problem studied herein, the techniques developed will serve as a prescriptive guide in developing fast and accurate dimensionally reduced models of nonlinear systems, and eventually as a tool for adaptive dimension-reduction in numerical modeling. The results are especially relevant in the aerospace industry for the design of thin structures such as beams, panels, and shells, which are all capable of spatio-temporally complex dynamic responses that are difficult and computationally expensive to model.

Structural Genomics of Protein Phosphatases

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

Almo,S.; Bonanno, J.; Sauder, J.

The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS Protein Structure Initiative (PSI) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of all human protein phosphatases and protein phosphatases from biomedically-relevant pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcriptionalmore » regulation, regulation of major signaling pathways, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise to provide an unprecedented database and materials repository for structure-guided experimental and computational discovery of inhibitors for all classes of protein phosphatases.« less

Hormonal profile impact on female sexual function in young women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Craina, Marius; Pater, Liana; Pater, Flavius

2014-12-01

Female sexual function is dependent, in physiological milieu upon hormonal impulses: estradiol, testosterone, cortisol, progesterone, prolactin and TSH. Out study tries to appreciate the impact of testosterone, estradiol and prolactin, the major hormones involved in the sexual response, on the normal sexual function. This parameter is approximated by the value of the total FSFI score, a validated international structured interview.

Vegetation response to large scale disturbance in a southern Appalachian forest: Hurricane Opal and salvage logging

Treesearch

Katherine J. Elliott; Stephanie L. Hitchcock; Lisa Krueger

2002-01-01

Disturbance such as catastrophic windthrow can play a major role in the structure and composition of southern Appalachian forests. We report effects of Hurricane Opal followed by salvage logging on vegetation dynamics (regeneration, composition, and diversity) the first three years after disturbance at the Coweeta Hydrologic Laboratory in western North Carolina. The...

Worker Generated Issues, Critical Dialogue, and Praxis: A Freirean Approach to Developing Social Change Projects

ERIC Educational Resources Information Center

O'Brien, Tim

2009-01-01

The escalating crisis in capitalist relations around the world demands a variety of responses that unmask the confusing structures that perpetuate asymmetrical power relations, while reframing what is truly in the interests of the majority of people. Industrial unions in the U.S. have at times aspired to such an advocacy role, but currently offer…

Stream Nitrate Response to Different Burning Treatments in Southern Appalachian Forests

Treesearch

Barton D. Clinton; James M. Vose; Jennifer D. Knoepp; Katherine J. Elliott

2003-01-01

Southern Appalachian forests are undergoing considerable change due to altered disturbance regimes. For example, fire exclusion has had a major impact on the structure and function of pine-hardwood ecosystems. Recently, fire has been prescribed for a variety of applications: 1) stand-replacement in the form of a mimicked wildfire, 2) site-preparation as part of a fell-...

Symptom changes in five dimensions of the Positive and Negative Syndrome Scale in refractory psychosis.

PubMed

Woodward, Todd S; Jung, Kwanghee; Smith, Geoffrey N; Hwang, Heungsun; Barr, Alasdair M; Procyshyn, Ric M; Flynn, Sean W; van der Gaag, Mark; Honer, William G

2014-12-01

Refractory psychosis units currently have little information regarding which symptoms profiles should be expected to respond to treatment. In the current study, we provide this information using structural equation modeling of Positive and Negative Syndrome Scale (PANSS) ratings at admission and discharge on a sample of 610 patients admitted to a treatment refractory psychosis program at a Canadian tertiary care unit between 1990 and 2011. The hypothesized five-dimensional structure of the PANSS fit the data well at both admission and discharge, and the latent variable scores are reported as a function of symptom dimension and diagnostic category. The results suggest that, overall, positive symptoms (POS) responded to treatment better than all other symptoms dimensions, but for the schizoaffective and bipolar groups, greater response on POS was observed relative to the schizophrenia and major depression groups. The major depression group showed the most improvement on negative symptoms and emotional distress, and the bipolar group showed the most improvement on disorganization. Schizophrenia was distinct from schizoaffective disorder in showing reduced treatment response on all symptom dimensions. These results can assist refractory psychosis units by providing information on how PANSS symptom dimensions respond to treatment and how this depends on diagnostic category.

Assessment of Galileo modal test results for mathematical model verification

NASA Technical Reports Server (NTRS)

Trubert, M.

1984-01-01

The modal test program for the Galileo Spacecraft was completed at the Jet Propulsion Laboratory in the summer of 1983. The multiple sine dwell method was used for the baseline test. The Galileo Spacecraft is a rather complex 2433 kg structure made of a central core on which seven major appendages representing 30 percent of the total mass are attached, resulting in a high modal density structure. The test revealed a strong nonlinearity in several major modes. This nonlinearity discovered in the course of the test necessitated running additional tests at the unusually high response levels of up to about 21 g. The high levels of response were required to obtain a model verification valid at the level of loads for which the spacecraft was designed. Because of the high modal density and the nonlinearity, correlation between the dynamic mathematical model and the test results becomes a difficult task. Significant changes in the pre-test analytical model are necessary to establish confidence in the upgraded analytical model used for the final load verification. This verification, using a test verified model, is required by NASA to fly the Galileo Spacecraft on the Shuttle/Centaur launch vehicle in 1986.

Principles and methodology for identification of fragrance allergens in consumer products.

PubMed

Gimenez-Arnau, A; Gimenez-Arnau, E; Serra-Baldrich, E; Lepoittevin, J-P; Camarasa, J G

2002-12-01

Fragrances contain several hundreds of different chemicals, a few major and many minor, which are responsible for the complexity of the odour. Fragrances are a major cause of allergic contact dermatitis. As a diagnostic tool, the current fragrance mix is very useful though not ideal. A 50-year-old woman presented with a pruriginous, erythematous eruption, characterized by papules, vesicles, exudation and crusting over the neck and chest. With the suspicion of fragrance allergy, patch testing was performed. Initially, the only positive reaction observed was with her own eau de toilette named Woman. The TRUE Test fragrance mix patch test was negative. Chemical fractionation of Woman perfume concentrate was combined with a sequenced patch testing procedure and with structure-activity relationship studies. Ingredients supplied by the manufacturer were also included in the study. Benzophenone-2, Lyral, alpha-hexyl cinnamic aldehyde and alpha-damascone were found to be responsible for the patient's contact allergy to the commercial product. These substances contain chemical structural alerts giving them antigenic ability. The common use of new chemicals to manufacture fragrances, and the increased number of patients sensitive to them but with negative fragrance mix reactions, makes it necessary to identify new potential fragrance sensitizers in commercial products.

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

Rasmussen, Søren G.F.; DeVree, Brian T; Zou, Yaozhong

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β 2 adrenergic receptor (β 2AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β 2AR and nucleotide-free Gs heterotrimer. The principal interactions between the βmore » 2AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β 2AR include a 14Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.« less

Structure of Black Male Students Academic Achievement in Science

NASA Astrophysics Data System (ADS)

Rascoe, Barbara

Educational policies and practices have been largely unsuccessful in closing the achievement gap between Black and White students "Schwartz, 2001". This achievement gap is especially problematic for Black students in science "Maton, Hrabrowski, - Schmitt, 2000. Given the fact that the Black-White achievement gap is still an enigma, the purpose of this article is to address the Black female-Black male academic achievement gap in science majors. Addressing barriers that Black male students may experience as college science and engineering majors, this article presents marketing strategies relative to politics, emotional intelligence, and issues with respect to how science teaching, and Black male students' responses to it, are different. Many Black male students may need to experience a paradigm shift, which structures and enhances their science achievement. Paradigm shifts are necessary because exceptional academic ability and motivation are not enough to get Black males from their first year in a science, technology, education, and mathematics "STEM" major to a bachelor's degree in science and engineering. The conclusions focus on the balance of truth-slippery slopes concerning the confluence of science teachers' further ado and Black male students' theories, methods, and values that position their academic achievement in science and engineering majors.

Development of a Novel Method for Determination of Residual Stresses in a Friction Stir Weld

NASA Technical Reports Server (NTRS)

Reynolds, Anthony P.

2001-01-01

Material constitutive properties, which describe the mechanical behavior of a material under loading, are vital to the design and implementation of engineering materials. For homogeneous materials, the standard process for determining these properties is the tensile test, which is used to measure the material stress-strain response. However, a majority of the applications for engineering materials involve the use of heterogeneous materials and structures (i.e. alloys, welded components) that exhibit heterogeneity on a global or local level. Regardless of the scale of heterogeneity, the overall response of the material or structure is dependent on the response of each of the constituents. Therefore, in order to produce materials and structures that perform in the best possible manner, the properties of the constituents that make up the heterogeneous material must be thoroughly examined. When materials exhibit heterogeneity on a local level, such as in alloys or particle/matrix composites, they are often treated as statistically homogenous and the resulting 'effective' properties may be determined through homogenization techniques. In the case of globally heterogeneous materials, such as weldments, the standard tensile test provides the global response but no information on what is Occurring locally within the different constituents. This information is necessary to improve the material processing as well as the end product.

Structural and functional annotation of the porcine immunome

PubMed Central

2013-01-01

Background The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems. Results The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome. Conclusions This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response. PMID:23676093

Terrorism in Bulgaria.

PubMed

Shanduorkov, George

2003-01-01

The Republic of Bulgaria is one of the smallest countries in southeastern Europe and has little experience with terrorist acts. During the past 20 years, only nine terrorism-related events have been recorded in Bulgaria, and no unconventional weapons have been used. Factors contributing to terrorism in Bulgaria have been: (1) Communist Party domination of the government and political process from 1944 to 1989; (2) ethnic and religious conflicts between the Bulgarian Orthodox Christian majority and the Turkish Muslim minority from 1983 to 1987; and (3) the relatively high level of organized crime after the Communist regime ended in 1990. The structure and function of the Disaster Relief System in Bulgaria not only are focused on the prevention of terrorism, but also on preparedness for the emergency response to terrorism-related events. Institutional components of the Disaster Relief System structure responsible for the emergency response to terrorism-related events include: (1) the Government of Bulgaria; (2) the State Agency for Civil Protection with 28 regional directorates; (3) the Ministry of Health with five national hospitals, 28 regional hospitals, and 28 EMS systems; (4) the Ministry of Defense with special military units for response to unconventional terrorist events, including nuclear, biological, and chemical weapons; (5) the Ministry of Internal Affairs with 28 police departments, 28 fire departments, and specialized anti-terrorist units; and (6) the Bulgarian Red Cross. A major future challenge in Bulgaria is the prevention of terrorism through political stability, economic prosperity, ethnic and religious tolerance, and more effective measures against organized criminal activities. A related challenge will be to improve the level of preparedness of all components of Disaster Relief.

Cervical spine injuries, mechanisms, stability and AIS scores from vertical loading applied to military environments.

PubMed

Yoganandan, Narayan; Pintar, Frank A; Humm, John R; Maiman, Dennis J; Voo, Liming; Merkle, Andrew

2016-07-01

The purpose of this study was to determine injuries to osteo-ligamentous structures of cervical column, mechanisms, forces, severities and AIS scores from vertical accelerative loading. Seven human cadaver head-neck complexes (56.9 ± 9.5 years) were aligned based on seated the posture of military soldiers. Army combat helmets were used. Specimens were attached to a vertical accelerator to apply caudo-cephalad g-forces. They were accelerated with increasing insults. Intermittent palpation and radiography were done. A roof structure mimicking military vehicle interior was introduced after a series of tests and experiments were conducted following similar protocols. Upon injury detection, CT and dissection were done. Temporal force responses were extracted, peak forces and times of occurrence were obtained, injury severities were graded, and spine stability was determined. Injuries occurred in tests only when the roof structure was included. Responses were tri-phasic: initial thrust, secondary tensile, tertiary roof contact phases. Peak forces: 1364-4382 N, initial thrust, 165-169 N, secondary tensile, 868-3368 N tertiary helmet-head roof contact phases. Times of attainments: 5.3-9.6, 31.7-42.6, 55.0-70.8 ms. Injuries included fractures and joint disruptions. Multiple injuries occurred in all but one specimen. A majority of injury severities were AIS = 2. Spines were considered unstable in a majority of cases. Spine response was tri-phasic. Injuries occurred in roof contact tests with the helmeted head-neck specimen. Multiplicity and unstable nature of AIS = 2 level injuries, albeit at lower severities, might predispose the spine to long-term accelerated degenerative changes. Clinical protocols should include a careful evaluation of sub-catastrophic injuries in military patients.

The high velocity impact loading on symmetrical and woven hybrid composite laminates

NASA Astrophysics Data System (ADS)

Jin, Martin; Richardson, Mel; Zhang, Zhong Yi

2007-07-01

Space structures use fibre composite materials, due to their lightweight. This paper examines the impact response of symmetrical and hybrid composite laminates. Special attention is given to the stacking sequences used. The experimental study of structures has always provided a major contribution to our understanding. Even with the formidable growth in the use and capacity of computing power the need for experimental measurement is as compelling as ever. The design of hybrid composite structures is complicated by the number of design variables and the interaction of the constituents is the composite system. Since it is desirable to experimentally test the design and it is not practical to test a full scale model, the structural/material similitude concept is used to create a small scale model with a similar structural response. In the current study, experimental investigations were carried out to determine the response of four different combinations of hybrid laminates to low-velocity impact loading using an instrumented impact testing machine. Hybrid laminates were fabricated with twill weave carbon fabric and plain weave S2-glass fabric using vacuum assisted resin molding process with SC-15 epoxy resin system. Response of carbon/epoxy and glass/epoxy laminates was also investigated to compare with that of hybrid samples. Square laminates of size 100 mm and nominal thickness of 3 mm were subjected to low-velocity impact loading at four energy levels of 10, 20, 30 and 40 J. Results of the study indicate that there is considerable improvement in the load carrying capability of hybrid composites as compared to carbon/epoxy laminates with slight reduction in stiffness.

Responses of Baltic Sea Ice and Open-Water Natural Bacterial Communities to Salinity Change

PubMed Central

Kaartokallio, Hermanni; Laamanen, Maria; Sivonen, Kaarina

2005-01-01

To investigate the responses of Baltic Sea wintertime bacterial communities to changing salinity (5 to 26 practical salinity units), an experimental study was conducted. Bacterial communities of Baltic seawater and sea ice from a coastal site in southwest Finland were used in two batch culture experiments run for 17 or 18 days at 0°C. Bacterial abundance, cell volume, and leucine and thymidine incorporation were measured during the experiments. The bacterial community structure was assessed using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified partial 16S rRNA genes with sequencing of DGGE bands from initial communities and communities of day 10 or 13 of the experiment. The sea ice-derived bacterial community was metabolically more active than the open-water community at the start of the experiment. Ice-derived bacterial communities were able to adapt to salinity change with smaller effects on physiology and community structure, whereas in the open-water bacterial communities, the bacterial cell volume evolution, bacterial abundance, and community structure responses indicated the presence of salinity stress. The closest relatives for all eight partial 16S rRNA gene sequences obtained were either organisms found in polar sea ice and other cold habitats or those found in summertime Baltic seawater. All sequences except one were associated with the α- and γ-proteobacteria or the Cytophaga-Flavobacterium-Bacteroides group. The overall physiological and community structure responses were parallel in ice-derived and open-water bacterial assemblages, which points to a linkage between community structure and physiology. These results support previous assumptions of the role of salinity fluctuation as a major selective factor shaping the sea ice bacterial community structure. PMID:16085826

An Investigation into the Postbuckling Response of a Single Blade-Stiffened Composite Panel

NASA Astrophysics Data System (ADS)

Spediacci, Alexander Daniel

The large strength reserves of stiffened composite structures in the postbuckling range appeal to the aerospace industry because of the high strength-to weight-ratio. Design and analysis of these large-scale, complex structures is technical, and requires major computational effort. Using the building-block approach, a smaller, single-stringer panel can be a useful and efficient tool for initial design, and can reveal critical behavior of a larger, multi-stringer panel. A characterization, through finite element modeling, of buckling and postbuckling response of a single blade-stiffened composite panel is proposed. Several factors affecting buckling and postbuckling behavior are investigated, including specimen length, initial imperfections, mode switching, and skin stringer separation. Two specimens are repeatedly tested under quasi- static compression loading well into the postbuckling range, showing no sign of damage. The test data from the specimens are used to compare and validate the nonlinear finite element models, show good correlation with the models. Ultimately, this work will serve to demonstrate the safety of stiffened structures operating in the postbuckling range and allow for thinner, lighter structures, which can increase the overall efficiency of aircraft.

LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

DOE PAGES

Golczak, Marcin; Sears, Avery E.; Kiser, Philip D.; ...

2014-11-10

Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompaniedmore » by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.« less

Insect photoreceptor adaptations to night vision

PubMed Central

Honkanen, Anna; Salmela, Iikka; Weckström, Matti

2017-01-01

Night vision is ultimately about extracting information from a noisy visual input. Several species of nocturnal insects exhibit complex visually guided behaviour in conditions where most animals are practically blind. The compound eyes of nocturnal insects produce strong responses to single photons and process them into meaningful neural signals, which are amplified by specialized neuroanatomical structures. While a lot is known about the light responses and the anatomical structures that promote pooling of responses to increase sensitivity, there is still a dearth of knowledge on the physiology of night vision. Retinal photoreceptors form the first bottleneck for the transfer of visual information. In this review, we cover the basics of what is known about physiological adaptations of insect photoreceptors for low-light vision. We will also discuss major enigmas of some of the functional properties of nocturnal photoreceptors, and describe recent advances in methodologies that may help to solve them and broaden the field of insect vision research to new model animals. This article is part of the themed issue ‘Vision in dim light’. PMID:28193821

Oral Cancer Knowledge, Attitudes, and Practices among Dentists in Khartoum State, Sudan.

PubMed

Ahmed, Nada H M; Naidoo, Sudeshni

2017-11-18

The dental professions hold an important responsibility in the control of oral cancer and the early diagnosis highly depends on their knowledge. The present study was developed to assess the knowledge, attitude, and practice of dentists in Khartoum State regarding oral cancer prevention and early detection. An administered questionnaire was structured and sent to all licensed 130 dentists working in public dental clinics in Khartoum State. Responses to the questionnaire were analyzed using descriptive and analytical statistics. Although the majority of the dentists were knowledgeable about the major risk factors of oral cancer, more than half of the dentists reported they do not carry out any special examination to detect oral cancer in age 40 and above in asymptomatic patients. Dentists indicated their lack of training as the main barrier for conducting a comprehensive oral cancer examination. Interestingly, the vast majority of the dentists express their interest to have further oral cancer educational and training sessions. The findings of the present study suggested strongly that educational and training interventions are necessary to enhance preventive measures which may lead to reduce mortality and morbidity from oral cancer.

Comparative analysis of structural concrete Quality Assurance practices on nine nuclear and three fossil fuel power plant construction projects. Final summary report

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

Willenbrock, J.H.; Thomas, H.R. Jr.; Burati, J.J. Jr.

1978-12-01

A summary of two reports, COO/4120-1 and COO/4120-2, is given. A comparative analysis was made of the Quality Assurance practices related to the structural concrete phase on nine nuclear and three fossil fuel power plant projects which are (or have been) under construction in the United States in the past ten years. For the nuclear projects the analysis identified the response of each Quality Assurance program to the applicable criteria of 10 CFR Part 50, Appendix B as well as to the pertinent regulatory requirements and industry standards. For the fossil projects the analysis identified the response of each Qualitymore » Assurance program to criteria similar to those which were applicable in the nuclear situation. The major emphasis was placed on the construction aspects of the structural concrete phase of each project. The engineering and design aspects were examined whenever they interfaced with the construction aspects.« less

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

Nondestructive evaluation of composite materials - A design philosophy

NASA Technical Reports Server (NTRS)

Duke, J. C., Jr.; Henneke, E. G., II; Stinchcomb, W. W.; Reifsnider, K. L.

1984-01-01

Efficient and reliable structural design utilizing fiber reinforced composite materials may only be accomplished if the materials used may be nondestructively evaluated. There are two major reasons for this requirement: (1) composite materials are formed at the time the structure is fabricated and (2) at practical strain levels damage, changes in the condition of the material, that influence the structure's mechanical performance is present. The fundamental basis of such a nondestructive evaluation capability is presented. A discussion of means of assessing nondestructively the material condition as well as a damage mechanics theory that interprets the material condition in terms of its influence on the mechanical response, stiffness, strength and life is provided.

Coral community response to bleaching on a highly disturbed reef

PubMed Central

Guest, J. R.; Low, J.; Tun, K.; Wilson, B.; Ng, C.; Raingeard, D.; Ulstrup, K. E.; Tanzil, J. T. I.; Todd, P. A.; Toh, T. C.; McDougald, D.; Chou, L. M.; Steinberg, P. D.

2016-01-01

While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress. PMID:26876092

Coral community response to bleaching on a highly disturbed reef.

PubMed

Guest, J R; Low, J; Tun, K; Wilson, B; Ng, C; Raingeard, D; Ulstrup, K E; Tanzil, J T I; Todd, P A; Toh, T C; McDougald, D; Chou, L M; Steinberg, P D

2016-02-15

While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress.

Coral community response to bleaching on a highly disturbed reef

NASA Astrophysics Data System (ADS)

Guest, J. R.; Low, J.; Tun, K.; Wilson, B.; Ng, C.; Raingeard, D.; Ulstrup, K. E.; Tanzil, J. T. I.; Todd, P. A.; Toh, T. C.; McDougald, D.; Chou, L. M.; Steinberg, P. D.

2016-02-01

While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress.

The role of sustained observations and data co-management in Arctic Ocean governance

NASA Astrophysics Data System (ADS)

Eicken, H.; Lee, O. A.; Rupp, S. T.; Trainor, S.; Walsh, J. E.

2015-12-01

Rapid environmental change, a rise in maritime activities and resource development, and increasing engagement by non-Arctic nations are key to major shifts underway in Arctic social-environmental systems (SES). These shifts are triggering responses by policy makers, regulators and a range of other actors in the Arctic Ocean region. Arctic science can play an important role in informing such responses, in particular by (i) providing data from sustained observations to serve as indicators of change and major transitions and to inform regulatory and policy response; (ii) identifying linkages across subsystems of Arctic SES and across regions; (iii) providing predictions or scenarios of future states of Arctic SES; and (iv) informing adaptation action in response to rapid change. Policy responses to a changing Arctic are taking a multi-faceted approach by advancing international agreements through the Arctic Council (e.g., Search and Rescue Agreement), global forums (e.g., IMO Polar Code) or private sector instruments (e.g., ISO code for offshore structures). At the regional level, co-management of marine living resources involving local, indigenous stakeholders has proven effective. All of these approaches rely on scientific data and information for planning and decision-making. Examples from the Pacific Arctic sector illustrate how such relevant data is currently collected through a multitude of different government agencies, universities, and private entities. Its effective use in informing policy, planning and emergency response requires coordinated, sustained acquisition, common standards or best practices, and data sharing agreements - best achieved through data co-management approaches. For projections and scenarios of future states of Arctic SES, knowledge co-production that involves all relevant stakeholders and specifically addresses major sources of uncertainty is of particular relevance in an international context.

Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

PubMed

Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

2017-10-01

In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.

Examining drivers of the emissions embodied in trade

PubMed Central

Wu, Leying; Wang, Zheng

2017-01-01

Emissions embodied in provincial trade (EEPT) have important effects on provinces’ responsibilities for carbon emission reductions. Based on a multi-regional input-output model, we calculated EEPT for China’s 30 provinces in 2002, 2007 and 2010, and we attempted to determine the drivers of EEPT. The results showed that, during this period, the ratio of EEPT to production-based emissions increased over time, reaching 40.24% in 2010. In consideration of its important role in carbon emissions, we analyzed the factors attributable to EEPT through structure decomposition analysis. The decomposition results showed that final demand and carbon emission intensity were two major factors in EEPT, while the final demand in other provinces and the carbon emission intensity in the local province were major factors for Emissions embodied in provincial exports and the final demand in the local province and the carbon emission intensity in other provinces were major factors for Emissions embodied in provincial imports. Regarding the differences among the EEPT of different provinces, changes in the structure of trade were the primary reason. PMID:28426769

Liquid chromatography/mass spectrometry-based plasma metabolic profiling study of escitalopram in subjects with major depressive disorder.

PubMed

Bandu, Raju; Lee, Hyun Jeong; Lee, Hyeong Min; Ha, Tae Hyon; Lee, Heon-Jeong; Kim, Se Joo; Ha, Kyooseob; Kim, Kwang Pyo

2018-05-01

Liquid chromatography-mass spectrometry (LC-MS) method revealed the plasma metabolite profiles in major depressive disorder patients treated with escitalopram (ECTP) (n = 7). Depression severity was assessed according to the 17-item Hamilton Depression Rating Scale. Metabolic profiles were derived from major depressive disorder subject blood samples collected after ECTP treatment. Blood plasma was separated and processed in order to effectively extract metabolites, which were then analyzed using LC-MS. We identified 19 metabolites and elucidated their structures using LC-tandem MS (LC-MS/MS) combined with elemental compositions derived from accurate mass measurements. We further used online H/D exchange experiments to verify the structural elucidations of each metabolite. Identifying molecular metabolites may provide critical insights into the pharmacological and clinical effects of ECTP treatment and may also provide useful information informing the development of new antidepressant treatments. These detailed plasma metabolite analyses may also be used to identify optimal dose concentrations in psychopharmacotherapeutic treatment through drug monitoring, as well as forming the basis for response predictions in depressed subjects. Copyright © 2018 John Wiley & Sons, Ltd.

Ionizing radiation effects on CMOS imagers manufactured in deep submicron process

NASA Astrophysics Data System (ADS)

Goiffon, Vincent; Magnan, Pierre; Bernard, Frédéric; Rolland, Guy; Saint-Pé, Olivier; Huger, Nicolas; Corbière, Franck

2008-02-01

We present here a study on both CMOS sensors and elementary structures (photodiodes and in-pixel MOSFETs) manufactured in a deep submicron process dedicated to imaging. We designed a test chip made of one 128×128-3T-pixel array with 10 μm pitch and more than 120 isolated test structures including photodiodes and MOSFETs with various implants and different sizes. All these devices were exposed to ionizing radiation up to 100 krad and their responses were correlated to identify the CMOS sensor weaknesses. Characterizations in darkness and under illumination demonstrated that dark current increase is the major sensor degradation. Shallow trench isolation was identified to be responsible for this degradation as it increases the number of generation centers in photodiode depletion regions. Consequences on hardness assurance and hardening-by-design are discussed.

The Feasibility of a Cadre Approach to Mobilization

DTIC Science & Technology

1990-05-01

system, legislation was now required to structure and organize the force. Subsequentlythe Militia Act of 1792 was passsed and after being heavily...States was questioned. Thus, several legislative acts were passed between 1903 to 1933, which formulated the National Guard as it is known today, and...have to undergo major legislative revisions regarding the authority over the National Guard, its state versus national responsibilities, and the amount

The Loma Prieta, California, earthquake of October 17, 1989 - Public response: Chapter B in The Loma Prieta, California, earthquake of October 17, 1989: Societal Response (Professional Paper 1553)

USGS Publications Warehouse

Bolton, Patricia A.

1993-01-01

Major earthquakes provide seismologists and engineers an opportunity to examine the performance of the Earth and the man-made structures in response to the forces of the quake. So, too, do they provide social scientists an opportunity to delve into human responses evoked by the ground shaking and its physical consequences. The findings from such research can serve to guide the development and application of programs and practices designed to reduce death, injury, property losses, and social disruption in subsequent earthquakes. This chapter contains findings from studies focused mainly on public response to the Loma Prieta earthquake; that is, on the behavior and perceptions of the general population rather than on the activities of specific organizations or on the impact on procedures or policies. A major feature of several of these studies is that the information was collected from the population throughout the Bay area, not just from persons in the most badly damaged communities or who had suffered the greatest losses. This wide range serves to provide comparisons of behavior for those most directly affected by the earthquake with others who were less directly affected by it but still had to consider it very “close to home.”

Support Tool in the Diagnosis of Major Depressive Disorder

NASA Astrophysics Data System (ADS)

Nunes, Luciano Comin; Pinheiro, Plácido Rogério; Pequeno, Tarcísio Cavalcante; Pinheiro, Mirian Calíope Dantas

Major Depressive Disorder have been responsible for millions of professionals temporary removal, and even permanent, from diverse fields of activities around the world, generating damage to social, financial, productive systems and social security, and especially damage to the image of the individual and his family that these disorders produce in individuals who are patients, characteristics that make them stigmatized and discriminated into their society, making difficult their return to the production system. The lack of early diagnosis has provided reactive and late measures, only when the professional suffering psychological disorder is already showing signs of incapacity for working and social relationships. This article aims to assist in the decision making to establish early diagnosis of these types of psychological disorders. It presents a proposal for a hybrid model composed of expert system structured methodologies for decision support (Multi-Criteria Decision Analysis - MCDA) and representations of knowledge structured in logical rules of production and probabilities (Artificial Intelligence - AI).

Podocalyxin as a major pluripotent marker and novel keratan sulfate proteoglycan in human embryonic and induced pluripotent stem cells.

PubMed

Toyoda, Hidenao; Nagai, Yuko; Kojima, Aya; Kinoshita-Toyoda, Akiko

2017-04-01

Podocalyxin (PC) was first identified as a heavily sialylated transmembrane protein of glomerular podocytes. Recent studies suggest that PC is a remarkable glycoconjugate that acts as a universal glyco-carrier. The glycoforms of PC are responsible for multiple functions in normal tissue, human cancer cells, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). PC is employed as a major pluripotent marker of hESCs and hiPSCs. Among the general antibodies for human PC, TRA-1-60 and TRA-1-81 recognize the keratan sulfate (KS)-related structures. Therefore, It is worthwhile to summarize the outstanding chemical characteristic of PC, including the KS-related structures. Here, we review the glycoforms of PC and discuss the potential of PC as a novel KS proteoglycan in undifferentiated hESCs and hiPSCs.

Gene flow contributes to diversification of the major fungal pathogen Candida albicans.

PubMed

Ropars, Jeanne; Maufrais, Corinne; Diogo, Dorothée; Marcet-Houben, Marina; Perin, Aurélie; Sertour, Natacha; Mosca, Kevin; Permal, Emmanuelle; Laval, Guillaume; Bouchier, Christiane; Ma, Laurence; Schwartz, Katja; Voelz, Kerstin; May, Robin C; Poulain, Julie; Battail, Christophe; Wincker, Patrick; Borman, Andrew M; Chowdhary, Anuradha; Fan, Shangrong; Kim, Soo Hyun; Le Pape, Patrice; Romeo, Orazio; Shin, Jong Hee; Gabaldon, Toni; Sherlock, Gavin; Bougnoux, Marie-Elisabeth; d'Enfert, Christophe

2018-06-08

Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify.

Probabilistic simulation of uncertainties in thermal structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Shiao, Michael

1990-01-01

Development of probabilistic structural analysis methods for hot structures is a major activity at Lewis Research Center. It consists of five program elements: (1) probabilistic loads; (2) probabilistic finite element analysis; (3) probabilistic material behavior; (4) assessment of reliability and risk; and (5) probabilistic structural performance evaluation. Recent progress includes: (1) quantification of the effects of uncertainties for several variables on high pressure fuel turbopump (HPFT) blade temperature, pressure, and torque of the Space Shuttle Main Engine (SSME); (2) the evaluation of the cumulative distribution function for various structural response variables based on assumed uncertainties in primitive structural variables; (3) evaluation of the failure probability; (4) reliability and risk-cost assessment, and (5) an outline of an emerging approach for eventual hot structures certification. Collectively, the results demonstrate that the structural durability/reliability of hot structural components can be effectively evaluated in a formal probabilistic framework. In addition, the approach can be readily extended to computationally simulate certification of hot structures for aerospace environments.

Identification of the major human hepatic and placental enzymes responsible for the biotransformation of glyburide

PubMed Central

Zharikova, Olga L.; Fokina, Valentina M.; Nanovskaya, Tatiana N.; Hill, Ronald A.; Mattison, Donald R.; Hankins, Gary D.V.; Ahmed, Mahmoud S.

2014-01-01

One of the factors affecting the pharmacokinetics (PK) of a drug during pregnancy is the activity of hepatic and placental metabolizing enzymes. Recently, we reported on the biotransformation of glyburide by human hepatic and placental microsomes to six metabolites that are structurally identical between the two tissues. Two of the metabolites, 4-trans- (M1) and 3-cis-hydroxycyclohexyl glyburide (M2b), were previously identified in plasma and urine of patients treated with glyburide and are pharmacologically active. The aim of this investigation was to identify the major human hepatic and placental CYP450 isozymes responsible for the formation of each metabolite of glyburide. This was achieved by the use of chemical inhibitors selective for individual CYP isozymes and antibodies raised against them. The identification was confirmed by the kinetic constants for the biotransformation of glyburide by cDNA-expressed enzymes. The data revealed that the major hepatic isozymes responsible for the formation of each metabolite are as follows: CYP3A4 (ethylene-hydroxylated glyburide (M5), 3-trans-(M3) and 2-trans-(M4) cyclohexyl glyburide); CYP2C9 (M1, M2a( 4-cis-) and M2b); CYP2C8 (M1 and M2b); and CYP2C19 (M2a). Human placental microsomal CYP19/aromatase was the major isozyme responsible for the biotransformation of glyburide to predominantly M5. The formation of significant amounts of M5 by CYP19 in the placenta could render this metabolite more accessible to the fetal circulation. The multiplicity of enzymes biotransforming glyburide and the metabolites formed underscores the potential for its drug interactions in vivo. PMID:19679108

Identification of the major human hepatic and placental enzymes responsible for the biotransformation of glyburide.

PubMed

Zharikova, Olga L; Fokina, Valentina M; Nanovskaya, Tatiana N; Hill, Ronald A; Mattison, Donald R; Hankins, Gary D V; Ahmed, Mahmoud S

2009-12-15

One of the factors affecting the pharmacokinetics (PK) of a drug during pregnancy is the activity of hepatic and placental metabolizing enzymes. Recently, we reported on the biotransformation of glyburide by human hepatic and placental microsomes to six metabolites that are structurally identical between the two tissues. Two of the metabolites, 4-trans-(M1) and 3-cis-hydroxycyclohexyl glyburide (M2b), were previously identified in plasma and urine of patients treated with glyburide and are pharmacologically active. The aim of this investigation was to identify the major human hepatic and placental CYP450 isozymes responsible for the formation of each metabolite of glyburide. This was achieved by the use of chemical inhibitors selective for individual CYP isozymes and antibodies raised against them. The identification was confirmed by the kinetic constants for the biotransformation of glyburide by cDNA-expressed enzymes. The data revealed that the major hepatic isozymes responsible for the formation of each metabolite are as follows: CYP3A4 (ethylene-hydroxylated glyburide (M5), 3-trans-(M3) and 2-trans-(M4) cyclohexyl glyburide); CYP2C9 (M1, M2a (4-cis-) and M2b); CYP2C8 (M1 and M2b); and CYP2C19 (M2a). Human placental microsomal CYP19/aromatase was the major isozyme responsible for the biotransformation of glyburide to predominantly M5. The formation of significant amounts of M5 by CYP19 in the placenta could render this metabolite more accessible to the fetal circulation. The multiplicity of enzymes biotransforming glyburide and the metabolites formed underscores the potential for its drug interactions in vivo.

The development and evaluation of an internal workplace violence risk assessment protocol: one organization's experience.

PubMed

Heitt, Michael C; Tamburo, Melissa Back

2005-01-01

The creation and development of a Risk Assessment Team at a large urban university is presented as a case study, with particular focus on the role the Employee Assistance Program (EAP) plays in the multidisciplinary team. The structure of the team and differing roles and responsibilities of members will be discussed. A specific protocol for addressing incidents will be introduced, along with changes in the team ' response over time. Major lessons learned will be presented, as well as the challenges the team faces today, and discussion of areas for future research and evaluation.

High-resolution structure of infectious prion protein: the final frontier

PubMed Central

Diaz-Espinoza, Rodrigo; Soto, Claudio

2014-01-01

Prions are the proteinaceous infectious agents responsible for the transmission of prion diseases. The main or sole component of prions is the misfolded prion protein (PrPSc), which is able to template the conversion of the host’s natively folded form of the protein (PrPC). The detailed mechanism of prion replication and the high-resolution structure of PrPSc are unknown. The currently available information on PrPSc structure comes mostly from low-resolution biophysical techniques, which have resulted in quite divergent models. Recent advances in the production of infectious prions, using very pure recombinant protein, offer new hope for PrPSc structural studies. This review highlights the importance of, challenges for and recent progress toward elucidating the elusive structure of PrPSc, arguably the major pending milestone to reach in understanding prions. PMID:22472622

Identification and characterization of major cat allergen Fel d 1 mimotopes on filamentous phage carriers.

PubMed

Luzar, Jernej; Molek, Peter; Šilar, Mira; Korošec, Peter; Košnik, Mitja; Štrukelj, Borut; Lunder, Mojca

2016-03-01

Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conceptualizing violence for health and medical geography.

PubMed

DeVerteuil, Geoffrey

2015-05-01

Despite the fact that violence is a major threat to public health, the term itself is rarely considered as a phenomenon unto itself, and rarely figures explicitly in work by health and medical geographers. In response, I propose a definitionally and conceptually more robust approach to violence using a tripartite frame (interpersonal violence, structural violence, mass intentional violence) and suggest critical interventions through which to apply this more explicit and conceptually more robust approach: violence and embodiment via substance abuse in health geography, and structural violence via mental illness in medical geography. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conceptual optimization using genetic algorithms for tube in tube structures

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

Pârv, Bianca Roxana; Hulea, Radu; Mojolic, Cristian

2015-03-10

The purpose of this article is to optimize the tube in tube structural systems for tall buildings under the horizontal wind loads. It is well-known that the horizontal wind loads is the main criteria when choosing the structural system, the types and the dimensions of structural elements in the majority of tall buildings. Thus, the structural response of tall buildings under the horizontal wind loads will be analyzed for 40 story buildings and a total height of 120 meters; the horizontal dimensions will be 30m × 30m for the first two optimization problems and 15m × 15m for the third.more » The optimization problems will have the following as objective function the cross section area, as restrictions the displacement of the building< the admissible displacement (H/500), and as variables the cross section dimensions of the structural elements.« less

Broadly targeted CD8 + T cell responses restricted by major histocompatibility complex E

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

Hansen, Scott G.; Wu, Helen L.; Burwits, Benjamin J.

Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, nonclassical, MHC-Ib molecule with limited polymorphism primarily involved in regulation of NK cell reactivity via interaction with NKG2/CD94 receptors. We found that vaccination of rhesus macaques with Rh157.5/.4 gene-deleted rhesus Cytomegalovirus (RhCMV) vectors uniquely diverts MHC-E function to presentation of highly diverse peptide epitopes to CD8α/β + T cells, approximately 4 distinct epitopes per 100 amino acids, in all tested protein antigens. Computational structural analysis revealed that a relatively stable, open binding groove in MHC-E attains broad peptide binding specificity by imposing a similar backbone configuration on bound peptides withmore » few restrictions based on amino acid side chains. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, MHC-E-restricted CD8 + T cell responses have the potential to exploit pathogen immune evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.« less

Broadly targeted CD8 + T cell responses restricted by major histocompatibility complex E

DOE PAGES

Hansen, Scott G.; Wu, Helen L.; Burwits, Benjamin J.; ...

2016-02-12

Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, nonclassical, MHC-Ib molecule with limited polymorphism primarily involved in regulation of NK cell reactivity via interaction with NKG2/CD94 receptors. We found that vaccination of rhesus macaques with Rh157.5/.4 gene-deleted rhesus Cytomegalovirus (RhCMV) vectors uniquely diverts MHC-E function to presentation of highly diverse peptide epitopes to CD8α/β + T cells, approximately 4 distinct epitopes per 100 amino acids, in all tested protein antigens. Computational structural analysis revealed that a relatively stable, open binding groove in MHC-E attains broad peptide binding specificity by imposing a similar backbone configuration on bound peptides withmore » few restrictions based on amino acid side chains. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, MHC-E-restricted CD8 + T cell responses have the potential to exploit pathogen immune evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.« less

Using Response Surface Methods to Correlate the Modal Test of an Inflatable Test Article

NASA Technical Reports Server (NTRS)

Gupta, Anju

2013-01-01

This paper presents a practical application of response surface methods (RSM) to correlate a finite element model of a structural modal test. The test article is a quasi-cylindrical inflatable structure which primarily consists of a fabric weave, with an internal bladder and metallic bulkheads on either end. To mitigate model size, the fabric weave was simplified by representing it with shell elements. The task at hand is to represent the material behavior of the weave. The success of the model correlation is measured by comparing the four major modal frequencies of the analysis model to the four major modal frequencies of the test article. Given that only individual strap material properties were provided and material properties of the overall weave were not available, defining the material properties of the finite element model became very complex. First it was necessary to determine which material properties (modulus of elasticity in the hoop and longitudinal directions, shear modulus, Poisson's ratio, etc.) affected the modal frequencies. Then a Latin Hypercube of the parameter space was created to form an efficiently distributed finite case set. Each case was then analyzed with the results input into RSM. In the resulting response surface it was possible to see how each material parameter affected the modal frequencies of the analysis model. If the modal frequencies of the analysis model and its corresponding parameters match the test with acceptable accuracy, it can be said that the model correlation is successful.

Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

NASA Astrophysics Data System (ADS)

Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

2017-02-01

It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

Condition assessment of a highly porous limestone fortress: damage categories and structural integrity

NASA Astrophysics Data System (ADS)

Török, Ákos; Czinder, Balázs; Farkas, Orsolya; Görög, Péter; Kopecskó, Katalin; Lógó, János; Rozgonyi-Boissinot, Nikoletta; Vásárhelyi, Balázs

2016-04-01

An emblematic monument the Citadella fortress of Budapest has been studied in details to assess the condition of stone structure. The fortress is a large stone structure of 220 m in length and 60 m in width. The height of the porous limestone walls are in between 12-16 metres. The fortress was completed in 1854 but has been partly rebuilt due to changes in function and war related structural damages. The present paper provides an overview of the lithology, weathering forms and structural condition of the fortress related to a forthcoming restoration-reconstruction project. To assess the condition of stone both on site and laboratory analyses were performed. Lithological varieties were documented. Major identified lithotypes are porous oolitic limestone, less porous bioclastic limestone and fine grained highly porous limestone. To identify wet zones portable moisture meter was applied. Surface strength and weathering grade were also assessed using Schmidt hammer and Duroscop. Decay features were diagnosed and mapped. The most common forms are white weathering crusts, scaling and blistering of crusts as well as granular disintegration. Black weathering crusts were also recognized. Laboratory tests were focused on mechanical properties of stones and on mineralogical and chemical compositional analyses. Small samples of stone were collected and tested by optical microscopy, SEM-EDX, XRD and Thermogravimetric analyses. Laboratory analyses proved that the major salt responsible for the damage of external walls is gypsum, although significant amount of halite and hygroscopic salts were found both on the external walls and in the interior parts of the fortress. During structural analyses displacement of walls, tilting and major amount of cracks were recognized. Loss of material and subsidence also caused problems and at some places unstable wall sections were recognized.

A nonlinear cointegration approach with applications to structural health monitoring

NASA Astrophysics Data System (ADS)

Shi, H.; Worden, K.; Cross, E. J.

2016-09-01

One major obstacle to the implementation of structural health monitoring (SHM) is the effect of operational and environmental variabilities, which may corrupt the signal of structural degradation. Recently, an approach inspired from the community of econometrics, called cointegration, has been employed to eliminate the adverse influence from operational and environmental changes and still maintain sensitivity to structural damage. However, the linear nature of cointegration may limit its application when confronting nonlinear relations between system responses. This paper proposes a nonlinear cointegration method based on Gaussian process regression (GPR); the method is constructed under the Engle-Granger framework, and tests for unit root processes are conducted both before and after the GPR is applied. The proposed approach is examined with real engineering data from the monitoring of the Z24 Bridge.

Role of tectonic inheritance in the instauration of Tunisian Atlassic fold-and-thrust belt: Case of Bouhedma - Boudouaou structures

NASA Astrophysics Data System (ADS)

Ghanmi, Mohamed Abdelhamid; Ghanmi, Mohamed; Aridhi, Sabri; Ben Salem, Mohamed Sadok; Zargouni, Fouad

2016-07-01

Tectonic inversion in the Bouhedma-Boudouaou Mountains was investigated through recent field work and seismic lines interpretation calibrated with petroleum well data. Located to the Central-Southern Atlas of Tunisia, this area signed shortened intra-continental fold-and-thrust belts. Two dissymmetric anticlines characterize Bouhedma - Boudouaou major fold. These structures show a strong virgation respectively from E-W to NNE-SSW as a response to the interference between both tectonic inversion and tectonic inheritance. This complex geometry is driven by Mesozoic rifting, which marked an extensional inherited regime. A set of late Triassic-Early Jurassic E-W and NW-SE normal faults dipping respectively to the North and to the East seems to widely affect the overall geodynamic evolution of this domain. They result in major thickness changes across the hanging wall and the footwall blocks in response with the rifting activity. Tectonic inversion is inferred from convergence between African and European plates since late Cretaceous. During Serravalian - Tortonian event, NW-SE trending paroxysm led to: 1) folding of pre-inversion and syn-inversion strata, 2) reactivation of pre-existing normal faults to reverse ones and 3) orogeny of the main structures with NE-SW and E-W trending. The compressional feature still remains active during Quaternary event (Post-Villafranchian) with N-S trending compression. Contraction during inversion generates folding and internal deformation as well as Fault-Propagation-Fold and folding related strike.

Converting conformational changes to electrostatic energy in molecular motors: The energetics of ATP synthase.

PubMed

Strajbl, Marek; Shurki, Avital; Warshel, Arieh

2003-12-09

F1-ATPase is the catalytic component of the ATP synthase molecular machine responsible for most of the uphill synthesis of ATP in living systems. The enormous advances in biochemical and structural studies of this machine provide an opportunity for detailed understanding of the nature of its rotary mechanism. However, further quantitative progress in this direction requires development of reliable ways of translating the observed structural changes to the corresponding energies. This requirement is particularly challenging because we are dealing with a large system that couples major structural changes with a chemical process. The present work provides such a structure-function correlation by using the linear response approximation to describe the rotary mechanism. This approach allows one to evaluate the energy of transitions between different conformational states by considering only the changes in the corresponding electrostatic energies of the ligands. The relevant energetics are also obtained by calculating the linear response approximation-based free energies of transferring the ligands from water to the different sites of F1-ATPase in their different conformational states. We also use the empirical valence bond approach to evaluate the actual free-energy profile for the ATP synthesis in the different conformational states of the system. Integrating the information from the different approaches provides a semiquantitative structure-function correlation for F1-ATPase. It is found that the conformational changes are converted to changes in the electrostatic interaction between the protein and its ligands, which drives the ATP synthesis.

Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar.

PubMed

Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F Javier

2010-12-01

Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar (Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

PubMed

Kim, Hei Sung; Yosipovitch, Gil

2013-04-01

Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.

Monitoring of wind load and response for cable-supported bridges in Hong Kong

NASA Astrophysics Data System (ADS)

Wong, Kai-yuen; Chan, Wai-Yee K.; Man, King-Leung

2001-08-01

Structural health monitoring for the three cable-supported bridges located in the West of Hong Kong or the Tsing Ma Control Area has been carried out since the opening of these bridges to public traffic. The three cable-supported bridges are referred to as the Tsing Ma (suspension) Bridge, the Kap Shui Mun (cable-stayed) Bridge and the Ting Kau (cable-stayed) Bridge. The structural health monitoring works involved are classified as six monitoring categories, namely, wind load and response, temperature load and response, traffic load and response, geometrical configuration monitoring, strains and stresses/forces monitoring and global dynamic characteristics monitoring. As wind loads and responses had been a major concern in the design and construction stages, this paper therefore outlines the work of wind load and response monitoring on Tsing Ma, Kap Shui Mun and Ting Kau Bridges. The paper starts with a brief description of the sensory systems. The description includes the layout and performance requirements of sensory systems for wind load and responses monitoring. Typical results of wind load and response monitoring in graphical forms are then presented. These graphical forms include the plots of wind rose diagrams, wind incidences vs wind speeds, wind turbulence intensities, wind power spectra, gust wind factors, coefficient of terrain roughness, extreme wind analyses, deck deflections/rotations vs wind speeds, acceleration spectra, acceleration/displacement contours, and stress demand ratios. Finally conclusions on wind load and response monitoring on the three cable-supported bridges are drawn.

Genome-wide identification, expression analysis of auxin-responsive GH3 family genes in maize (Zea mays L.) under abiotic stresses.

PubMed

Feng, Shangguo; Yue, Runqing; Tao, Sun; Yang, Yanjun; Zhang, Lei; Xu, Mingfeng; Wang, Huizhong; Shen, Chenjia

2015-09-01

Auxin is involved in different aspects of plant growth and development by regulating the expression of auxin-responsive family genes. As one of the three major auxin-responsive families, GH3 (Gretchen Hagen3) genes participate in auxin homeostasis by catalyzing auxin conjugation and bounding free indole-3-acetic acid (IAA) to amino acids. However, how GH3 genes function in responses to abiotic stresses and various hormones in maize is largely unknown. Here, the latest updated maize (Zea mays L.) reference genome sequence was used to characterize and analyze the ZmGH3 family genes from maize. The results showed that 13 ZmGH3 genes were mapped on five maize chromosomes (total 10 chromosomes). Highly diversified gene structures and tissue-specific expression patterns suggested the possibility of function diversification for these genes in response to environmental stresses and hormone stimuli. The expression patterns of ZmGH3 genes are responsive to several abiotic stresses (salt, drought and cadmium) and major stress-related hormones (abscisic acid, salicylic acid and jasmonic acid). Various environmental factors suppress auxin free IAA contents in maize roots suggesting that these abiotic stresses and hormones might alter GH3-mediated auxin levels. The responsiveness of ZmGH3 genes to a wide range of abiotic stresses and stress-related hormones suggested that ZmGH3s are involved in maize tolerance to environmental stresses. © 2014 Institute of Botany, Chinese Academy of Sciences.

Electrodynamic response of the type-II Weyl semimetal YbMnBi 2

DOE PAGES

Chinotti, M.; Pal, A.; Ren, W. J.; ...

2016-12-01

Weyl fermions play a major role in quantum field theory but have been quite elusive as fundamental particles. These quasi-two-dimensional bismuth layers based materials were recently designed and provide an arena for studying the interplay between anisotropic Dirac fermions, magnetism, and structural changes, allowing the formation of Weyl fermions in condensed matter. We perform an optical investigation of YbMnBi 2 , a representative type-II Weyl semimetal, and contrast its excitation spectrum with the optical response of the more conventional semimetal EuMnBi 2 . This comparative study allows us to disentangle the optical fingerprints of type-II Weyl fermions, but also challengesmore » the present theoretical understanding of their electrodynamic response.« less

Anomalous Anticipatory Responses in Networked Random Data

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

Nelson, Roger D.; Bancel, Peter A.

2006-10-16

We examine an 8-year archive of synchronized, parallel time series of random data from a world spanning network of physical random event generators (REGs). The archive is a publicly accessible matrix of normally distributed 200-bit sums recorded at 1 Hz which extends from August 1998 to the present. The primary question is whether these data show non-random structure associated with major events such as natural or man-made disasters, terrible accidents, or grand celebrations. Secondarily, we examine the time course of apparently correlated responses. Statistical analyses of the data reveal consistent evidence that events which strongly affect people engender small butmore » significant effects. These include suggestions of anticipatory responses in some cases, leading to a series of specialized analyses to assess possible non-random structure preceding precisely timed events. A focused examination of data collected around the time of earthquakes with Richter magnitude 6 and greater reveals non-random structure with a number of intriguing, potentially important features. Anomalous effects in the REG data are seen only when the corresponding earthquakes occur in populated areas. No structure is found if they occur in the oceans. We infer that an important contributor to the effect is the relevance of the earthquake to humans. Epoch averaging reveals evidence for changes in the data some hours prior to the main temblor, suggestive of reverse causation.« less

Mass spectrometry based structural analysis and systems immunoproteomics strategies for deciphering the host response to endotoxin.

PubMed

Khan, Mohd M; Ernst, Orna; Sun, Jing; Fraser, Iain D C; Ernst, Robert K; Goodlett, David R; Nita-Lazar, Aleksandra

2018-06-24

One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4 (TLR4)/myeloid differentiation factor-2 (MD2) complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress, and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry (MS)-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, MS-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications (PTMs). Copyright © 2018. Published by Elsevier Ltd.

2S Albumin Storage Proteins: What Makes them Food Allergens?

PubMed

Moreno, F Javier; Clemente, Alfonso

2008-01-01

2S albumin storage proteins are becoming of increasing interest in nutritional and clinical studies as they have been reported as major food allergens in seeds of many mono- and di-cotyledonous plants. This review describes the main biochemical, structural and functional properties of these proteins thought to play a role in determining their potential allergenicity. 2S albumins are considered to sensitize directly via the gastrointestinal tract (GIT). The high stability of their intrinsic protein structure, dominated by a well-conserved skeleton of cysteine residues, to the harsh conditions present in the GIT suggests that these proteins are able to cross the gut mucosal barrier to sensitize the mucosal immune system and/or elicit an allergic response. The flexible and solvent-exposed hypervariable region of these proteins is immunodominant and has the ability to bind IgE from allergic patients sera. Several linear IgE-binding epitopes of 2S albumins spanning this region have been described to play a major role in allergenicity; the role of conformational epitopes of these proteins in food allergy is far from being understood and need to be investigated. Finally, the interaction of these proteins with other components of the food matrix might influence the absorption rates of immunologically reactive 2S albumins but also in their immune response.

2S Albumin Storage Proteins: What Makes them Food Allergens?

PubMed Central

Moreno, F. Javier; Clemente, Alfonso

2008-01-01

2S albumin storage proteins are becoming of increasing interest in nutritional and clinical studies as they have been reported as major food allergens in seeds of many mono- and di-cotyledonous plants. This review describes the main biochemical, structural and functional properties of these proteins thought to play a role in determining their potential allergenicity. 2S albumins are considered to sensitize directly via the gastrointestinal tract (GIT). The high stability of their intrinsic protein structure, dominated by a well-conserved skeleton of cysteine residues, to the harsh conditions present in the GIT suggests that these proteins are able to cross the gut mucosal barrier to sensitize the mucosal immune system and/or elicit an allergic response. The flexible and solvent-exposed hypervariable region of these proteins is immunodominant and has the ability to bind IgE from allergic patients´ sera. Several linear IgE-binding epitopes of 2S albumins spanning this region have been described to play a major role in allergenicity; the role of conformational epitopes of these proteins in food allergy is far from being understood and need to be investigated. Finally, the interaction of these proteins with other components of the food matrix might influence the absorption rates of immunologically reactive 2S albumins but also in their immune response. PMID:18949071

Plant growth in elevated CO2 alters mitochondrial number and chloroplast fine structure

PubMed Central

Griffin, Kevin L.; Anderson, O. Roger; Gastrich, Mary D.; Lewis, James D.; Lin, Guanghui; Schuster, William; Seemann, Jeffrey R.; Tissue, David T.; Turnbull, Matthew H.; Whitehead, David

2001-01-01

With increasing interest in the effects of elevated atmospheric CO2 on plant growth and the global carbon balance, there is a need for greater understanding of how plants respond to variations in atmospheric partial pressure of CO2. Our research shows that elevated CO2 produces significant fine structural changes in major cellular organelles that appear to be an important component of the metabolic responses of plants to this global change. Nine species (representing seven plant families) in several experimental facilities with different CO2-dosing technologies were examined. Growth in elevated CO2 increased numbers of mitochondria per unit cell area by 1.3–2.4 times the number in control plants grown in lower CO2 and produced a statistically significant increase in the amount of chloroplast stroma (nonappressed) thylakoid membranes compared with those in lower CO2 treatments. There was no observable change in size of the mitochondria. However, in contrast to the CO2 effect on mitochondrial number, elevated CO2 promoted a decrease in the rate of mass-based dark respiration. These changes may reflect a major shift in plant metabolism and energy balance that may help to explain enhanced plant productivity in response to elevated atmospheric CO2 concentrations. PMID:11226263

Advances in Campylobacter biology and implications for biotechnological applications.

PubMed

Jeon, Byeonghwa; Muraoka, Wayne T; Zhang, Qijing

2010-05-01

Campylobacter jejuni is a major foodborne pathogen of animal origin and a leading cause of bacterial gastroenteritis in humans. During the past decade, especially since the publication of the first C. jejuni genome sequence, major advances have been made in understanding the pathobiology and physiology of this organism. It is apparent that C. jejuni utilizes sophisticated mechanisms for effective colonization of the intestinal tracts in various animal species. Although Campylobacter is fragile in the environment and requires fastidious growth conditions, it exhibits great flexibility in the adaptation to various habitats including the gastrointestinal tract. This high adaptability is attributable to its genetically, metabolically and phenotypically diverse population structure and its ability to change in response to various challenges. Unlike other enteric pathogens, such as Escherichia coli and Salmonella, Campylobacter is unable to utilize exogenous glucose and mainly depends on the catabolism of amino acids as a carbon source. Campylobacter proves highly mutable in response to antibiotic treatments and possesses eukaryote-like dual protein glycosylation systems, which modify flagella and other surface proteins with specific sugar structures. In this review we will summarize the distinct biological traits of Campylobacter and discuss the potential biotechnological approaches that can be developed to control this enteric pathogen. © 2009 The Authors. Journal compilation © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

Wood production response to climate change will depend critically on forest composition and structure.

PubMed

Coomes, David A; Flores, Olivier; Holdaway, Robert; Jucker, Tommaso; Lines, Emily R; Vanderwel, Mark C

2014-12-01

Established forests currently function as a major carbon sink, sequestering as woody biomass about 26% of global fossil fuel emissions. Whether forests continue to act as a global sink will depend on many factors, including the response of aboveground wood production (AWP; MgC ha(-1 ) yr(-1) ) to climate change. Here, we explore how AWP in New Zealand's natural forests is likely to change. We start by statistically modelling the present-day growth of 97 199 individual trees within 1070 permanently marked inventory plots as a function of tree size, competitive neighbourhood and climate. We then use these growth models to identify the factors that most influence present-day AWP and to predict responses to medium-term climate change under different assumptions. We find that if the composition and structure of New Zealand's forests were to remain unchanged over the next 30 years, then AWP would increase by 6-23%, primarily as a result of physiological responses to warmer temperatures (with no appreciable effect of changing rainfall). However, if warmth-requiring trees were able to migrate into currently cooler areas and if denser canopies were able to form, then a different AWP response is likely: forests growing in the cool mountain environments would show a 30% increase in AWP, while those in the lowland would hardly respond (on average, -3% when mean annual temperature exceeds 8.0 °C). We conclude that response of wood production to anthropogenic climate change is not only dependent on the physiological responses of individual trees, but is highly contingent on whether forests adjust in composition and structure. © 2014 John Wiley & Sons Ltd.

The impact of additional cytogenetic abnormalities at diagnosis and during therapy with tyrosine kinase inhibitors in Chronic Myeloid Leukaemia.

PubMed

Crisan, A M; Coriu, D; Arion, C; Colita, A; Jardan, C

2015-01-01

Chronic Myeloid Leukemia's (CML) treatment was optimized since the development of tyrosine kinase inhibitors (TKI) and an increased overall survival during TKI was noticed. During the TKI era, protocols for assessing response and resistance to treatment were developed. Additional chromosomal abnormalities (ACAs) are strongly associated with disease progression but their prognostic impact and influence on treatment response are yet to be defined. The aim of this study was to analyze the impact of ACAs on time to achieve complete cytogenetic response (CCyR), treatment and overall survival. Since 2005 until 2013, the data from the Hematology and Bone Marrow Transplantation Department of Fundeni Clinical Institute was collected. In this observational retrospective single centre study, 28 CML patients with ACAs at diagnosis and during TKI treatment were included. From ACAs at diagnosis group, the most frequent major route ACAs were trisomy 8, trisomy 19 and second Philadelphia (Ph) chromosome and the most frequent minor route ACAs were monosomies and structural abnormalities (inversions and translocations). From the ACAs during the TKI group, the most frequent major route cytogenetic abnormalities in Ph positive and negative cells were trisomy 8, trisomy 19 and second Ph chromosome and the most frequent minor route cytogenetic abnormalities in Ph positive and negative cells were marker chromosomes and structural abnormalities (inversions, translocations and dicentric chromosomes). In both groups, the time to CCyR was longer and long-term results were inferior in comparison with standard patients but the differences were not significant and in accordance to published data. The 12 months follow-up after the study's end showed that 26 patients were alive and in long-term CCyR and 2 deaths were reported. CML = Chronic Myeloid Leukemia, BCR-ABL1 = Break Cluster Region - Abelson gene, TKI = tyrosine kinase inhibitor treatment, ACAs = additional cytogenetic abnormalities, CCyR = complete cytogenetic response, PCyR = partial cytogenetic response, mCyR = minor cytogenetic response, MMR = major molecular response, HSCT = hematopoietic stem cell transplant, HLA = human leukocyte antigens, CP = chronic phase, AP = accelerated phase, BP = blast phase, OS = overall survival, CBA = chromosome banding analysis, +8 = trisomy 8, i(17q) = isochromosome (17q), +Ph = second Philadelphia chromosome, -7 = monosomy 7, -17 = monosomy 17, +17 = trisomy 17, -21 = monosomy 21, +21 = trisomy 21, -Y = loss of Y chromosome, ELN = European LeukemiaNet, IMA600 = Imatinib 600 mg daily, IMA400 = Imatinib 400 mg daily, NILO600 = Nilotinib 600 mg daily, DASA100 = Dasatinib 100mg daily, DASA140 = Dasatinib 140 mg daily.

Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain

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

Tan, Kemin; Deatherage Kaiser, Brooke L.; Wu, Ruiying

S. Typhimurium can induce both humoral and cell-mediated responses when establishing itself in the host. These responses are primarily stimulated against the lipopolysaccharide and major outer membrane (OM) proteins of the bacterium. OmpA is one of these major OM proteins. It comprises a N-terminal eight-stranded -barrel membrane domain and a C-terminal so-called OmpA C-terminal domain (OmpACTD). The OmpACTD and its homologs are believed to bind to peptidoglycan (PG) within the periplasm, maintaining bacterial osmotic homeostasis and modulating the permeability and integrity of the outer membrane. Here we present the structures of two forms of the OmpACTD of S. Typhimurium (STOmpACTD)more » and one structure of the less-studied OmpACTD of Borrelia burgdorferi (BbOmpACTD). In the open form of STOmpACTD, an aspartic acid residue from a long 2-3 loop points into the binding pocket, suggesting that an anion group such as a carboxylate group from PG is favored at the binding site. In the closed form of STOmpACTD and in the structure of BbOmpACTD, a sulfate group from the crystallization buffer is tightly bound at the equivalent site. The differences between the closed and open forms of STOmpACTD, suggest a large conformational change that includes an extension of 3 helix by ordering a part of 2-3 loop. We suggest that the sulfate anion observed in these structures mimics the carboxylate group of PG when bound to STOmpACTD. In addition, the binding of PG or a ligand mimic may enhance dimerization of STOmpACTD, or possibly that of full length STOmpA.« less

Similar local order in disordered fluorite and aperiodic pyrochlore structures

DOE PAGES

Shamblin, Jacob; Tracy, Cameron; Palomares, Raul; ...

2017-10-01

A major challenge to understanding the response of materials to extreme environments (e.g., nuclear fuels/waste forms and fusion materials) is to unravel the processes by which a material can incorporate atomic-scale disorder, and at the same time, remain crystalline. While it has long been known that all condensed matter, even liquids and glasses, possess short-range order, the relation between fully-ordered, disordered, and aperiodic structures over multiple length scales is not well understood. For example, when defects are introduced (via pressure or irradiation) into materials adopting the pyrochlore structure, these complex oxides either disorder over specific crystallographic sites, remaining crystalline, ormore » become aperiodic. Here we present neutron total scattering results characterizing the irradiation response of two pyrochlores, one that is known to disorder (Er2Sn2O7) and the other to amorphize (Dy2Sn2O7) under ion irradiation. The results demonstrate that in both cases, the local pyrochlore structure is transformed into similar short range configurations that are best fit by the orthorhombic weberite structure, even though the two compositions have distinctly different structures, aperiodic vs. disordered-crystalline, at longer length scales. Thus, a material's resistance to amorphization may not depend primarily on local defect formation energies, but rather on the structure's compatibility with meso-scale modulations of the local order in a way that maintains long-range periodicity.« less

Rise of CC398 Lineage of Staphylococcus aureus among Infective Endocarditis Isolates Revealed by Two Consecutive Population-Based Studies in France

PubMed Central

Tristan, Anne; Rasigade, Jean-Philippe; Ruizendaal, Esmée; Laurent, Frédéric; Bes, Michèle; Meugnier, Hélène; Lina, Gérard; Etienne, Jerome; Celard, Marie; Tattevin, Pierre; Monecke, Stefan; Le Moing, Vincent; Vandenesch, François

2012-01-01

Staphylococcus aureus isolates from two prospective studies on infective endocarditis (IE) conducted in 1999 and 2008 and isolated from non-IE bacteremia collected in 2006 were spa-typed and their virulence factors were analyzed with a microarray. Both populations were genetically diverse, with no virulence factors or genotypes significantly more associated with the IE isolates compared with the non-IE isolates. The population structure of the IE isolates did not change much between 1999 and 2008, with the exception of the appearance of CC398 methicillin-susceptible Staphylococcus aureus (MSSA) isolates responsible for 5.6% of all cases in 2008. In 1999, this lineage was responsible for no cases. The increasing prevalence of S. aureus in IE is apparently not the result of a major change in staphylococcal population structure over time, with the exception of the emerging CC398 MSSA lineage. PMID:23272091

Structure and Function of the 26S Proteasome.

PubMed

Bard, Jared A M; Goodall, Ellen A; Greene, Eric R; Jonsson, Erik; Dong, Ken C; Martin, Andreas

2018-06-20

As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.

Bacterial Iron–Sulfur Regulatory Proteins As Biological Sensor-Switches

PubMed Central

Crack, Jason C.; Green, Jeffrey; Hutchings, Matthew I.; Thomson, Andrew J.

2012-01-01

Abstract Significance: In recent years, bacterial iron–sulfur cluster proteins that function as regulators of gene transcription have emerged as a major new group. In all cases, the cluster acts as a sensor of the environment and enables the organism to adapt to the prevailing conditions. This can range from mounting a response to oxidative or nitrosative stress to switching between anaerobic and aerobic respiratory pathways. The sensitivity of these ancient cofactors to small molecule reactive oxygen and nitrogen species, in particular, makes them ideally suited to function as sensors. Recent Advances: An important challenge is to obtain mechanistic and structural information about how these regulators function and, in particular, how the chemistry occurring at the cluster drives the subsequent regulatory response. For several regulators, including FNR, SoxR, NsrR, IscR, and Wbl proteins, major advances in understanding have been gained recently and these are reviewed here. Critical Issues: A common theme emerging from these studies is that the sensitivity and specificity of the cluster of each regulatory protein must be exquisitely controlled by the protein environment of the cluster. Future Directions: A major future challenge is to determine, for a range of regulators, the key factors for achieving control of sensitivity/specificity. Such information will lead, eventually, to a system understanding of stress response, which often involves more than one regulator. Antioxid. Redox Signal. 17, 1215–1231. PMID:22239203

Responsibility and burden from the perspective of seniors' family caregivers: a qualitative study in Shanghai, China.

PubMed

Zeng, Li; Zhu, Xiaoping; Meng, Xianmei; Mao, Yafen; Wu, Qian; Shi, Yan; Zhou, Lanshu

2014-01-01

This study aimed to explore the experience of seniors' family caregivers with regarding the responsibility, burden and support needs during caregiving in Shanghai, China. An exploratory, descriptive, qualitative design was used and a semi-structure interview was conducted. A convenience sample of 11 participants in two community service centers in Shanghai was recruited. Data saturation guided the size of the sample. The Colaizzi method of empirical phenomenology was used for interviewing and analyzing data obtained from 11 caregivers. Three major themes were found: It is a hard work; It is my responsibility; Social support is not enough. The findings of the study are practical and helpful for health care providers to develop appropriate caregiver support services, to balance the responsibility and burden of caregivers, and to consider the factors influencing the utility of support services.

Social Variations in Perceived Parenting Styles among Norwegian Adolescents.

PubMed

Elstad, Jon Ivar; Stefansen, Kari

2014-01-01

Previous research has documented the associations between parenting and parenting styles and child and adolescent outcomes. Little is known, however, about the social structuring of parenting in contemporary Nordic welfare states. A possible hypothesis is that socioeconomic variations in parenting styles in present-day Norway will be small because of material affluence, limited income inequality, and an active welfare state. This study examines social variations in parenting as perceived by Norwegian adolescents ( N  = 1362), with a focus on four parenting style dimensions: responsiveness, demandingness, neglecting, and intrusive. Responsiveness seems to capture major divisions in parenting. Adolescents in families with fewer economic resources experienced their parents as somewhat less responsive, but responsiveness was not related to parents' education. Low parental education was on the other hand associated with perceptions of parents as neglecting and intrusive. Viewing parents as demanding did neither vary with parental education nor with family economy. Substantial variations in parenting styles persist in present-day Norway, and these variations correspond moderately with the families' placement in the social structure. Indicators of parenting and parenting styles may be useful indicators of some aspects of child and adolescent well-being.

Association analysis of SIGMAR1 with major depressive disorder and SSRI response.

PubMed

Kishi, Taro; Yoshimura, Reiji; Okochi, Tomo; Fukuo, Yasuhisa; Kitajima, Tsuyoshi; Okumura, Takenori; Tsunoka, Tomoko; Kawashima, Kunihiro; Yamanouchi, Yoshio; Kinoshita, Yoko; Umene-Nakano, Wakako; Naitoh, Hiroshi; Nakamura, Jun; Ozaki, Norio; Iwata, Nakao

2010-06-01

Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results. (c) 2010. Published by Elsevier Ltd. All rights reserved.

Free-decay time-domain modal identification for large space structures

NASA Technical Reports Server (NTRS)

Kim, Hyoung M.; Vanhorn, David A.; Doiron, Harold H.

1992-01-01

Concept definition studies for the Modal Identification Experiment (MIE), a proposed space flight experiment for the Space Station Freedom (SSF), have demonstrated advantages and compatibility of free-decay time-domain modal identification techniques with the on-orbit operational constraints of large space structures. Since practical experience with modal identification using actual free-decay responses of large space structures is very limited, several numerical and test data reduction studies were conducted. Major issues and solutions were addressed, including closely-spaced modes, wide frequency range of interest, data acquisition errors, sampling delay, excitation limitations, nonlinearities, and unknown disturbances during free-decay data acquisition. The data processing strategies developed in these studies were applied to numerical simulations of the MIE, test data from a deployable truss, and launch vehicle flight data. Results of these studies indicate free-decay time-domain modal identification methods can provide accurate modal parameters necessary to characterize the structural dynamics of large space structures.

Consequences of extinction in tropical peat-forming vegetation of the Middle to Late Pennsylvanian (Westphalian-Stephanian)

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

DiMichele, W.A.; Phillips, T.L.

1992-01-01

Peat-forming environments (coals) were major landscape elements of the Pennsylvanian tropics. Mires reached a pantropical zenith during the 9 Ma of the Westphalian when long intervals of similar vegetation were separated by short intervals of rapid change. Differences between successive vegetation types primarily reflect different proportions of several major habitat-specific subfloras within which species turnover occurred. A hierarchy of organizational levels is suggested in which biotic interactions helped structure and constrain patterns of species replacement. Lycopsids were the framework trees of nearly all Westphalian mires; tree ferns and pteridosperm were important subdominants by the late Westphalian. Environmental changes, largely climatic,more » during the Westphalian-Stephanian transition resulted in extinction of most mire species, particularly trees. Tree ferns dominated Stephanian mires following a short transitional period of small-lycopsid and fern abundance. Tree ferns were cheaply constructed opportunists and their rise in abundance coincided with an increase in species numbers throughout tropical lowlands. Within mires there was an increase in physical size of plants from several major lineages. The structure and dynamics of Stephanian mires differed from the Westphalian; previously sharp distinctions between mires and other lowland floras diminished. The Westphalian to Stephanian vegetational changes suggest that ecosystems can display a brittle'' response to environmental change. Such threshold responses are a likely consequences of levels of extinction high enough to disrupt ecosystem fabric. The success of opportunistic lineages following loss of indigenous mire vegetation constitutes a secondary replacement, with establishment of a new equilibrium within hundreds of thousands of years.« less

Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection

PubMed Central

Farnell, Edward J.; Tyagi, Nidhi; Ryan, Stephanie; Chalmers, Iain W.; Pinot de Moira, Angela; Jones, Frances M.; Wawrzyniak, Jakub; Fitzsimmons, Colin M.; Tukahebwa, Edridah M.; Furnham, Nicholas; Maizels, Rick M.; Dunne, David W.

2015-01-01

The IgE response has been associated with both allergic reactions and immunity to metazoan parasites. Recently, we hypothesized that all environmental allergens bear structural homology to IgE-binding antigens from metazoan parasites and that this homology defines the relatively small number of protein families containing allergenic targets. In this study, known allergen structures (Pfam domains) from major environmental allergen families were used to predict allergen-like (SmProfilin, SmVAL-6, SmLipocalin, SmHSP20, Sm triosephosphate isomerase, SmThioredoxin, Sm superoxide dismutase, SmCyclophilin, and Sm phosphoglycerate kinase) and non-allergen-like [Sm dynein light chain (SmDLC), SmAldolase SmAK, SmUbiquitin, and Sm14-3-3] proteins in Schistosoma mansoni. Recombinant antigens were produced in Escherichia coli and IgG1, IgG4, and IgE responses against them measured in a cohort of people (n = 222) infected with S. mansoni. All allergen-like antigens were targeted by IgE responses in infected subjects, whilst IgE responses to the non-allergen-like antigens, SmAK, SmUbiquitin, and Sm14-3-3 were essentially absent being of both low prevalence and magnitude. Two new IgE-binding Pfam domain families, not previously described in allergen family databases, were also found, with prevalent IgE responses against SmDLC (PF01221) and SmAldolase (PF00274). Finally, it was demonstrated that immunoregulatory serological processes typically associated with allergens also occurred in responses to allergen-like proteins in S. mansoni infections, including the production of IgG4 in people responding with IgE and the down-regulation of IgE in response to increased antigen exposure from S. mansoni eggs. This study establishes that structures of known allergens can be used to predict IgE responses against homologous parasite allergen-like molecules (parallergens) and that serological responses with IgE/IgG4 to parallergens mirror those seen against allergens, supporting our hypothesis that allergenicity is rooted in expression of certain protein domain families in metazoan parasites. PMID:25691884

Evolutionary conservatism explains increasing relatedness of plant communities along a flooding gradient.

PubMed

Tanentzap, Andrew J; Lee, William G

2017-01-01

Abiotic filters have been found either to increase or reduce evolutionary relatedness in plant communities, making it difficult to generalize responses of this major feature of biodiversity to future environmental change. Here, we hypothesized that the responses of phylogenetic structure to environmental change ultimately depend on how species have evolved traits for tolerating the resulting abiotic changes. Working within ephemeral wetlands, we tested whether species were increasingly related as flooding duration intensified. We also identified the mechanisms underlying increased relatedness by measuring root aerenchyma volume (RAV), a trait which promotes waterlogging tolerance. We found that species-specific responses to flooding explained most of the variation in occurrence for 63 vascular plant species across 5170 plots. For a subset of 22 species, we attributed these responses to variation in RAV. Large RAV specifically increased occurrence when flooding lasted for longer time periods, because large RAV reduced above-ground biomass loss. As large RAV was evolutionarily conserved within obligate wetland species, communities were more phylogenetically related as flooding increased. Our study shows how reconstructing the evolutionary history of traits that influence the responses of species to environmental change can help to predict future patterns in phylogenetic structure. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Whither vaccines?

PubMed

Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A

2017-06-01

Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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

Chinotti, M.; Pal, A.; Ren, W. J.

Weyl fermions play a major role in quantum field theory but have been quite elusive as fundamental particles. These quasi-two-dimensional bismuth layers based materials were recently designed and provide an arena for studying the interplay between anisotropic Dirac fermions, magnetism, and structural changes, allowing the formation of Weyl fermions in condensed matter. We perform an optical investigation of YbMnBi 2 , a representative type-II Weyl semimetal, and contrast its excitation spectrum with the optical response of the more conventional semimetal EuMnBi 2 . This comparative study allows us to disentangle the optical fingerprints of type-II Weyl fermions, but also challengesmore » the present theoretical understanding of their electrodynamic response.« less

Structural health monitoring to detect the presence, location and magnitude of structural damage in cadaveric porcine spines.

PubMed

Kawchuk, Gregory Neil; Decker, Colleen; Dolan, Ryan; Carey, Jason

2009-01-19

Structural health monitoring has been used successfully to identify defects in civil infrastructure and aerospace applications. Given that the majority of low back pain is thought to be mechanical in nature, our objective was to determine if structural health monitoring techniques could be employed successfully to identify the presence, location and magnitude of structural alterations within the spine. In six eviscerated cadaveric pigs, bone screws were drilled into the anterior bodies of L1-L5 and tri-axial accelerometers fixed to each spinous process. Vibration was then applied to the L3 spinous and frequency response functions obtained from each sensor axis before and after specific alterations of spinal structure. These alterations were produced at four unique locations and included (1) use of a cable tie to link anterior bone pins together and (2) progressive disc sectioning. Eighty percent of all data were used to train a neural network while the remaining data were used to test the network's ability to distinguish between structural states. The presence, location and magnitude of structural change within the spine was identified correctly in 5030/5040 possible neural network decisions. The diagnostic sensitivity and specificity of this technique ranged from 0.994 to 1.000. These results indicate that there is sufficient information embedded in frequency response data to identify the presence, location and magnitude of specific structural changes in the spine. If these techniques can be evolved for human use, structural health monitoring may provide a new approach toward understanding the underlying relations between spinal structure and function.

Acceptance and utilisation of the Incident Command System in first response and allied disciplines: an Ohio study.

PubMed

Decker, Russell J

2011-10-01

In response to the terrorist attacks of September 11th, 2001, an effort was made to establish a common and uniform command structure for use by the nation's first responder organisations, as well as those disciplines generally expected to assist first responders during a major incident or disaster. The result was the issuance of the National Incident Management System1 or NIMS by the US Department of Homeland Security in 2004. Included in the NIMS document was an embracing of the Incident Command System or ICS, long utilised in the fire service for the effective management of emergency response. The NIMS doctrine also identified certain allied disciplines that needed to adopt this new system for responding to major events. Some of these disciplines included specialised first response units, such as, bomb squads and hazardous materials teams. Other partner disciplines not usually associated with emergency response to include public health and public works were also included. This study will attempt to look at a single component of NIMS, specifically the Incident Command System, and measure its acceptance and utilisation by first responder organisations and selected allied disciplines in the state of Ohio. This is particularly important at this time since the US government is being forced to reduce budgets significantly and determine which laudable policies and programmes will be cut.

Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

PubMed

Yang, Xin-hua; Huang, Jia; Lan, Yong; Zhu, Cui-ying; Liu, Xiao-qun; Wang, Ye-fei; Cheung, Eric F C; Xie, Guang-rong; Chan, Raymond C K

2016-01-04

Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD. We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making. Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls. These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiant energy during infrared neural stimulation at the target structure

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Rajguru, Suhrud; Stafford, Ryan; Stock, Stuart R.

2013-03-01

Infrared neural stimulation (INS) describes a method, by which an infrared laser is used to stimulate neurons. The major benefit of INS over stimulating neurons with electrical current is its spatial selectivity. To translate the technique into a clinical application it is important to know the energy required to stimulate the neural structure. With this study we provide measurements of the radiant exposure, at the target structure that is required to stimulate the auditory neurons. Flat polished fibers were inserted into scala tympani so that the spiral ganglion was in front of the optical fiber. Angle polished fibers were inserted along scala tympani, and rotating the beveled surface of the fiber allowed the radiation beam to be directed perpendicular to the spiral ganglion. The radiant exposure for stimulation at the modiolus for flat and angle polished fibers averaged 6.78+/-2.15 mJ/cm2. With the angle polished fibers, a 90º change in the orientation of the optical beam from an orientation that resulted in an INS-evoked maximum response, resulted in a 50% drop in the response amplitude. When the orientation of the beam was changed by 180º, such that it was directed opposite to the orientation with the maxima, minimum response amplitude was observed.

WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System

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

Herrou, Julien; Czyż, Daniel M.; Willett, Jonathan W.

ABSTRACT The general stress response (GSR) system of the intracellular pathogenBrucella abortuscontrols the transcription of approximately 100 genes in response to a range of stress cues. The core genetic regulatory components of the GSR are required forB. abortussurvival under nonoptimal growth conditionsin vitroand for maintenance of chronic infection in anin vivomouse model. The functions of the majority of the genes in the GSR transcriptional regulon remain undefined.bab1_1070is among the most highly regulated genes in this regulon: its transcription is activated 20- to 30-fold by the GSR system under oxidative conditionsin vitro. We have solved crystal structures of Bab1_1070 and demonstratemore » that it forms a homotetrameric complex that resembles those of WrbA-type NADH:quinone oxidoreductases, which are members of the flavodoxin protein family. However,B. abortusWrbA-relatedprotein (WrpA) does not bind flavin cofactors with a high affinity and does not function as an NADH:quinone oxidoreductasein vitro. Soaking crystals with flavin mononucleotide (FMN) revealed a likely low-affinity binding site adjacent to the canonical WrbA flavin binding site. Deletion ofwrpA(ΔwrpA) does not compromise cell survival under acute oxidative stressin vitroor attenuate infection in cell-based or mouse models. However, a ΔwrpAstrain does elicit increased splenomegaly in a mouse model, suggesting that WrpA modulatesB. abortusinteraction with its mammalian host. Despite high structural homology with canonical WrbA proteins, we propose thatB. abortusWrpA represents a functionally distinct member of the diverse flavodoxin family. IMPORTANCEBrucella abortusis an etiological agent of brucellosis, which is among the most common zoonotic diseases worldwide. The general stress response (GSR) regulatory system ofB. abortuscontrols the transcription of approximately 100 genes and is required for maintenance of chronic infection in a murine model; the majority of GSR-regulated genes remain uncharacterized. We presentin vitroandin vivofunctional and structural analyses of WrpA, whose expression is strongly induced by GSR under oxidative conditions. Though WrpA is structurally related to NADH:quinone oxidoreductases, it does not bind redox cofactors in solution, nor does it exhibit oxidoreductase activityin vitro. However, WrpA does affect spleen inflammation in a murine infection model. Our data provide evidence that WrpA forms a new functional class of WrbA/flavodoxin family proteins.« less

Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

PubMed

Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

2016-06-01

Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure of bacterial lipopolysaccharides.

PubMed

Caroff, Martine; Karibian, Doris

2003-11-14

Bacterial lipopolysaccharides are the major components of the outer surface of Gram-negative bacteria They are often of interest in medicine for their immunomodulatory properties. In small amounts they can be beneficial, but in larger amounts they may cause endotoxic shock. Although they share a common architecture, their structural details exert a strong influence on their activity. These molecules comprise: a lipid moiety, called lipid A, which is considered to be the endotoxic component, a glycosidic part consisting of a core of approximately 10 monosaccharides and, in "smooth-type" lipopolysaccharides, a third region, named O-chain, consisting of repetitive subunits of one to eight monosaccharides responsible for much of the immunospecificity of the bacterial cell.

Study on the Weak Stress in Flexural MEMS Cantilever

NASA Astrophysics Data System (ADS)

Ge, Yuetao; Ren, Yan

2018-03-01

In order to design a better piezoresistive MEMS cantilever beam, especially for cantilever beams that will detect weak forces or will be subjected to weak forces, this paper uses study on the weak stress in flexural MEMS cantilever. The sensor design structure, divided into protective layer, piezoresistive layer, support layer. The protective layer is responsible for protecting the piezoresistive layer so that the varistor is insulated from the outside; the piezoresistive layer is used to make the varistor; the support layer forms the main part of the cantilever beam, the majority of the cantilever beam. This paper has some value for cantilever multilayer structure design and cantilever beam size design.

Satellite radars for geologic mapping in tropical regions

NASA Technical Reports Server (NTRS)

Ford, J. P.; Sabins, F. F.

1987-01-01

This paper presents interpretations of the satellite radar images of cloud-covered portions of Indonesia and Amazonia obtained from NASA's Shuttle imaging radar experiments in 1981 (SIR-A) and 1984 (SIR-B). It was found that different terrain categories observed from distinctive image textures correlate well with major lithologic associations. The images show geologic structures at regional and local scales. The SIR-B images of East Kalimantan, Indonesia, reveal structural features and terrain distributions that had been overlooked or not perceived in previous surface mapping. Variability in radar response from the vegetation cover is interpretable only in coastal areas or alluvial areas that are relatively level.

Thigmo Responses: The Fungal Sense of Touch.

PubMed

Almeida, Mariana Cruz; Brand, Alexandra C

2017-04-01

The growth and development of most fungi take place on a two-dimensional surface or within a three-dimensional matrix. The fungal sense of touch is therefore critical for fungi in the interpretation of their environment and often signals the switch to a new developmental state. Contact sensing, or thigmo-based responses, include thigmo differentiation, such as the induction of invasion structures by plant pathogens in response to topography; thigmonasty, where contact with a motile prey rapidly triggers its capture; and thigmotropism, where the direction of hyphal growth is guided by physical features in the environment. Like plants and some bacteria, fungi grow as walled cells. Despite the well-demonstrated importance of thigmo responses in numerous stages of fungal growth and development, it is not known how fungal cells sense contact through the relatively rigid structure of the cell wall. However, while sensing mechanisms at the molecular level are not entirely understood, the downstream signaling pathways that are activated by contact sensing are being elucidated. In the majority of cases, the response to contact is complemented by chemical cues and both are required, either sequentially or simultaneously, to elicit normal developmental responses. The importance of a sense of touch in the lifestyles and development of diverse fungi is highlighted in this review, and the candidate molecular mechanisms that may be involved in fungal contact sensing are discussed.

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

Gross, P.M.; Kadekaro, M.; Andrews, D.W.

The subfornical organ is a major receptor area for one of the principal stimuli of thirst, the octapeptide, angiotensin II. In conscious water-sated rats, the authors examined the effects of intravenous infusion of angiotensin II on the rate of glucose utilization in the subfornical organ and in structures anatomically and functionally connected with it. Angiotensin II produced pressor and drinking responses and increased glucose utilization selectively in the subfornical organ and pituitary neural lobe and in no other brain structure. Treatment with the angiotensin II antagonist, sar1-leu8-angiotensin II, before intravenous administration of angiotensin II prevented metabolic stimulation of the subfornicalmore » organ and neural lobe. Captopril, an inhibitor of angiotensin-converting enzyme, reduced subfornical organ glucose metabolism to a level similar to that found in control animals. These results demonstrate that peripheral angiotensin II stimulates glucose metabolism in the subfornical organ under conditions in which it provokes drinking and pressor responses. The findings suggest that circulating angiotensin II is responsible for the high rate of glucose utilization observed in the subfornical organ of Brattleboro rats homozygous for diabetes insipidus.« less

Insect photoreceptor adaptations to night vision.

PubMed

Honkanen, Anna; Immonen, Esa-Ville; Salmela, Iikka; Heimonen, Kyösti; Weckström, Matti

2017-04-05

Night vision is ultimately about extracting information from a noisy visual input. Several species of nocturnal insects exhibit complex visually guided behaviour in conditions where most animals are practically blind. The compound eyes of nocturnal insects produce strong responses to single photons and process them into meaningful neural signals, which are amplified by specialized neuroanatomical structures. While a lot is known about the light responses and the anatomical structures that promote pooling of responses to increase sensitivity, there is still a dearth of knowledge on the physiology of night vision. Retinal photoreceptors form the first bottleneck for the transfer of visual information. In this review, we cover the basics of what is known about physiological adaptations of insect photoreceptors for low-light vision. We will also discuss major enigmas of some of the functional properties of nocturnal photoreceptors, and describe recent advances in methodologies that may help to solve them and broaden the field of insect vision research to new model animals.This article is part of the themed issue 'Vision in dim light'. © 2017 The Author(s).

Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

PubMed

Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

2016-08-08

The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

Resveratrol in peanuts.

PubMed

Sales, Jocelyn M; Resurreccion, Anna V A

2014-01-01

Peanuts are important dietary food source of resveratrol with potent antioxidant properties implicated in reducing risk of cancer, cardiovascular and Alzheimer's disease, and delaying aging. Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound produced in response to a variety of biotic and abiotic stresses. This paper is a review of trans-resveratrol and related stilbenes from peanuts--their chemical structures, mechanisms for their biosynthesis, and concentrations in comparison with other major food sources. It will also discuss trans-resveratrol's absorption, bioavailability, and major health benefits; processes to enhance their biosynthesis in peanuts by biotic and abiotic stresses; process optimization for enhanced levels in peanuts and their potential food applications; and methods used for its extraction and analysis.

Effect of Ground Motion Characteristics on the Seismic Response of a Monumental Concrete Arch Bridge

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

Caglayan, B. Ozden; Ozakgul, Kadir; Tezer, Ovunc

2008-07-08

Railway network in Turkey dates back to more than a hundred years ago and according to official records, there are approximately 18,000 railway bridges with spans varying between 50 cm up to 150 meters. One of them is a monumental concrete arch bridge with a total length of 210 meters having three major spans of 30 meters and a height of 65 meters, located in an earthquake-prone region in southern part of the country. Three-dimensional finite element model of the bridge was generated using a commercially available general finite element analysis software and based on the outcomes of a seriesmore » of in-depth acceleration measurements that were conducted on-site, the model was refined. Types of ground motion records were used to investigate the seismic response and vulnerability of this massive structure in order to provide information regarding (i) damage-susceptible regions of the structure for monitoring purposes, and, (ii) seismic loads to be taken into account during evaluation and possible strengthening phases for this type of structures.« less

The proteome of the wool cuticle.

PubMed

Koehn, Henning; Clerens, Stefan; Deb-Choudhury, Santanu; Morton, James D; Dyer, Jolon M; Plowman, Jeffrey E

2010-06-04

The cuticle is responsible for important wool fiber characteristics such as handle and abrasion resistance, which impact on the fiber's performance in both interior and apparel textiles. The cuticle proteome, however, is not well understood due to the difficulty in isolating pure wool cuticle and its significant resistance to protein extraction, which is attributed to the presence of extensive disulfide and isopeptide cross-linking. We investigated the proteome of highly pure Merino wool cuticle using a combined strategy of chemical and enzymatic digestion and identified 108 proteins, including proteins responsible for a variety of cellular processes. The majority of identified proteins belonged to keratin and nonkeratin protein families known to play an important role in molecular assembly and cellular structure. Keratin-associated, intermediate filament and cytoskeletal keratin proteins were identified as the most prominent keratinous cuticular constituents, while histones, tubulins, and desmosomes were the key nonkeratin structural proteins. We conclude that a variety of proteins contribute to cuticle structure and fiber characteristics, and that the keratinous protein families of IFPs and KAPs represent the most important cuticular constituents.

Molecular, mesoscopic and microscopic structure evolution during amylase digestion of maize starch granules.

PubMed

Shrestha, Ashok K; Blazek, Jaroslav; Flanagan, Bernadine M; Dhital, Sushil; Larroque, Oscar; Morell, Matthew K; Gilbert, Elliot P; Gidley, Michael J

2012-09-01

Cereal starch granules with high (>50%) amylose content are a promising source of nutritionally desirable resistant starch, i.e. starch that escapes digestion in the small intestine, but the structural features responsible are not fully understood. We report the effects of partial enzyme digestion of maize starch granules on amylopectin branch length profiles, double and single helix contents, gelatinisation properties, crystallinity and lamellar periodicity. Comparing results for three maize starches (27, 57, and 84% amylose) that differ in both structural features and amylase-sensitivity allows conclusions to be drawn concerning the rate-determining features operating under the digestion conditions used. All starches are found to be digested by a side-by-side mechanism in which there is no major preference during enzyme attack for amylopectin branch lengths, helix form, crystallinity or lamellar organisation. We conclude that the major factor controlling enzyme susceptibility is granule architecture, with shorter length scales not playing a major role as inferred from the largely invariant nature of numerous structural measures during the digestion process (XRD, NMR, SAXS, DSC, FACE). Results are consistent with digestion rates being controlled by restricted diffusion of enzymes within densely packed granular structures, with an effective surface area for enzyme attack determined by external dimensions (57 or 84% amylose - relatively slow) or internal channels and pores (27% amylose - relatively fast). Although the process of granule digestion is to a first approximation non-discriminatory with respect to structure at molecular and mesoscopic length scales, secondary effects noted include (i) partial crystallisation of V-type helices during digestion of 27% amylose starch, (ii) preferential hydrolysis of long amylopectin branches during the early stage hydrolysis of 27% and 57% but not 84% amylose starches, linked with disruption of lamellar repeating structure and (iii) partial B-type recrystallisation after prolonged enzyme incubation for 57% and 84% amylose starches but not 27% amylose starch. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mapping the Structural and Dynamical Features of Multiple p53 DNA Binding Domains: Insights into Loop 1 Intrinsic Dynamics

PubMed Central

Lukman, Suryani; Lane, David P.; Verma, Chandra S.

2013-01-01

The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD). In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs). Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3). Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart). Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1) a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2) possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site. PMID:24324553

Structure-based design of broadly protective group a streptococcal M protein-based vaccines.

PubMed

Dale, James B; Smeesters, Pierre R; Courtney, Harry S; Penfound, Thomas A; Hohn, Claudia M; Smith, Jeremy C; Baudry, Jerome Y

2017-01-03

A major obstacle to the development of broadly protective M protein-based group A streptococcal (GAS) vaccines is the variability within the N-terminal epitopes that evoke potent bactericidal antibodies. The concept of M type-specific protective immune responses has recently been challenged based on the observation that multivalent M protein vaccines elicited cross-reactive bactericidal antibodies against a number of non-vaccine M types of GAS. Additionally, a new "cluster-based" typing system of 175M proteins identified a limited number of clusters containing closely related M proteins. In the current study, we used the emm cluster typing system, in combination with computational structure-based peptide modeling, as a novel approach to the design of potentially broadly protective M protein-based vaccines. M protein sequences (AA 16-50) from the E4 cluster containing 17 emm types of GAS were analyzed using de novo 3-D structure prediction tools and the resulting structures subjected to chemical diversity analysis to identify sequences that were the most representative of the 3-D physicochemical properties of the M peptides in the cluster. Five peptides that spanned the range of physicochemical attributes of all 17 peptides were used to formulate synthetic and recombinant vaccines. Rabbit antisera were assayed for antibodies that cross-reacted with E4 peptides and whole bacteria by ELISA and for bactericidal activity against all E4GAS. The synthetic vaccine rabbit antisera reacted with all 17 E4M peptides and demonstrated bactericidal activity against 15/17 E4GAS. A recombinant hybrid vaccine containing the same E4 peptides also elicited antibodies that cross-reacted with all E4M peptides. Comprehensive studies using structure-based design may result in a broadly protective M peptide vaccine that will elicit cluster-specific and emm type-specific antibody responses against the majority of clinically relevant emm types of GAS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Major Histocompatibility Complex I Expression by Motor Neurons and Its Implication in Amyotrophic Lateral Sclerosis

PubMed Central

Nardo, Giovanni; Trolese, Maria Chiara; Bendotti, Caterina

2016-01-01

Neuronal expression of major histocompatibility complex I (MHCI)-related molecules in adults and during CNS diseases is involved in the synaptic plasticity and axonal regeneration with mechanisms either dependent or independent of their immune functions. Motor neurons are highly responsive in triggering the expression of MHCI molecules during normal aging or following insults and diseases, and this has implications in the synaptic controls, axonal regeneration, and neuromuscular junction stability of these neurons. We recently reported that MHCI and immunoproteasome are strongly activated in spinal motor neurons and their peripheral motor axon in a mouse model of familial amyotrophic lateral sclerosis (ALS) during the course of the disease. This response was prominent in ALS mice with slower disease progression in which the axonal structure and function was better preserved than in fast-progressing mice. This review summarizes and discusses our observations in the light of knowledge about the possible role of MHCI in motor neurons providing additional insight into the pathophysiology of ALS. PMID:27379008

Social responsibilities of a physician: reflections of Major General S L Bhatia (1891-1981).

PubMed

Hegde, Radhika; Vaz, Mario

2017-01-01

This paper examines various documents written by Major General SL Bhatia CIE, MC, IMS from the 1920s to the1960s on the "Social Responsibilities of a Physician". His reflections are of historical significance, since they provide us with an insight into the challenges confronting the people who attempted to rebuild a nation plagued by poverty resulting from fractured agricultural growth, a feudalistic social structure and the regional inequalities that accompany it, and prolonged imperial rule, among other things. Bhatia's thoughts, especially on medical education and the condition of rural health and sanitation, enable us to understand India's present health concerns through the prism of the past. The writings of Bhatia, who lived during a period of transition in India, reflect an understanding of health issues from the perspectives both of an administrator and a physician struggling to meet the challenges of a nascent nation. He insisted on rooting his medical teachings in the principles of the humanities and ethics.

Protein Delivery into Plant Cells: Toward In vivo Structural Biology

PubMed Central

Cedeño, Cesyen; Pauwels, Kris; Tompa, Peter

2017-01-01

Understanding the biologically relevant structural and functional behavior of proteins inside living plant cells is only possible through the combination of structural biology and cell biology. The state-of-the-art structural biology techniques are typically applied to molecules that are isolated from their native context. Although most experimental conditions can be easily controlled while dealing with an isolated, purified protein, a serious shortcoming of such in vitro work is that we cannot mimic the extremely complex intracellular environment in which the protein exists and functions. Therefore, it is highly desirable to investigate proteins in their natural habitat, i.e., within live cells. This is the major ambition of in-cell NMR, which aims to approach structure-function relationship under true in vivo conditions following delivery of labeled proteins into cells under physiological conditions. With a multidisciplinary approach that includes recombinant protein production, confocal fluorescence microscopy, nuclear magnetic resonance (NMR) spectroscopy and different intracellular protein delivery strategies, we explore the possibility to develop in-cell NMR studies in living plant cells. While we provide a comprehensive framework to set-up in-cell NMR, we identified the efficient intracellular introduction of isotope-labeled proteins as the major bottleneck. Based on experiments with the paradigmatic intrinsically disordered proteins (IDPs) Early Response to Dehydration protein 10 and 14, we also established the subcellular localization of ERD14 under abiotic stress. PMID:28469623

Relationships between nonlinear normal modes and response to random inputs

NASA Astrophysics Data System (ADS)

Schoneman, Joseph D.; Allen, Matthew S.; Kuether, Robert J.

2017-02-01

The ability to model nonlinear structures subject to random excitation is of key importance in designing hypersonic aircraft and other advanced aerospace vehicles. When a structure is linear, superposition can be used to construct its response to a known spectrum in terms of its linear modes. Superposition does not hold for a nonlinear system, but several works have shown that a system's dynamics can still be understood qualitatively in terms of its nonlinear normal modes (NNMs). This work investigates the connection between a structure's undamped nonlinear normal modes and the spectrum of its response to high amplitude random forcing. Two examples are investigated: a spring-mass system and a clamped-clamped beam modeled within a geometrically nonlinear finite element package. In both cases, an intimate connection is observed between the smeared peaks in the response spectrum and the frequency-energy dependence of the nonlinear normal modes. In order to understand the role of coupling between the underlying linear modes, reduced order models with and without modal coupling terms are used to separate the effect of each NNM's backbone from the nonlinear couplings that give rise to internal resonances. In the cases shown here, uncoupled, single-degree-of-freedom nonlinear models are found to predict major features in the response with reasonable accuracy; a highly inexpensive approximation such as this could be useful in design and optimization studies. More importantly, the results show that a reduced order model can be expected to give accurate results only if it is also capable of accurately predicting the frequency-energy dependence of the nonlinear modes that are excited.

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes

PubMed Central

Castoe, Todd A.; de Koning, A. P. Jason; Hall, Kathryn T.; Card, Daren C.; Schield, Drew R.; Fujita, Matthew K.; Ruggiero, Robert P.; Degner, Jack F.; Daza, Juan M.; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J.; Castoe, Jill M.; Fox, Samuel E.; Poole, Alex W.; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W.; Li, Qing; Schott, Ryan K.; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A.; Hoffmann, Federico G.; Bogden, Robert; Smith, Eric N.; Chang, Belinda S. W.; Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Richardson, Michael K.; Mackessy, Stephen P.; Bronikowski, Anne M.; Yandell, Mark; Warren, Wesley C.; Secor, Stephen M.; Pollock, David D.

2013-01-01

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome. PMID:24297902

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.

PubMed

Castoe, Todd A; de Koning, A P Jason; Hall, Kathryn T; Card, Daren C; Schield, Drew R; Fujita, Matthew K; Ruggiero, Robert P; Degner, Jack F; Daza, Juan M; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J; Castoe, Jill M; Fox, Samuel E; Poole, Alex W; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W; Li, Qing; Schott, Ryan K; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A; Hoffmann, Federico G; Bogden, Robert; Smith, Eric N; Chang, Belinda S W; Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Richardson, Michael K; Mackessy, Stephen P; Bronikowski, Anne M; Bronikowsi, Anne M; Yandell, Mark; Warren, Wesley C; Secor, Stephen M; Pollock, David D

2013-12-17

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

Identification of linear B-cell epitopes on goose parvovirus non-structural protein.

PubMed

Yu, Tian-Fei; Ma, Bo; Wang, Jun-Wei

2016-10-15

Goose parvovirus (GPV) infection can cause a highly contagious and lethal disease in goslings and muscovy ducklings which is widespread in all major goose (Anser anser) and Muscovy duck (Cairina moschata) farming countries, leading to a huge economic loss. Humoral immune responses play a major role in GPV immune protection during GPV infection. However, it is still unknown for the localization and immunological characteristics of B-cell epitopes on GPV non-structural protein (NSP). Therefore, in this study, the epitopes on the NSP of GPV were identified by means of overlapping peptides expressed in Escherichia coli in combination with Western blot. The results showed that the antigenic epitopes on the GPV NSP were predominantly localized in the C-terminal (aa 485-627), and especially, the fragment NS (498-532) was strongly positive. These results may facilitate future investigations on the function of NSP of GPV and the development of immunoassays for the diagnosis of GPV infection. Copyright © 2016. Published by Elsevier B.V.

Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their metabolites.

PubMed

Liu, Zhongfa; Chan, Kenneth K; Wang, Jeffrey J

2005-01-01

A detailed multi-stage (MSn) fragmentation study of cyclophosphamide (CP), ifosfamide (IF) and their major metabolites, using an ion-trap mass spectrometer and a Q-TOF mass spectrometer, was performed with the aid of specifically deuterium-labeled analogs. The analytes showed good responses in positive-ion electrospray mass spectrometry as [MH]+ ions. Tandem mass spectra revealed a wealth of structurally specific ions, allowing characterization of the fragmentation pathways of these analytes. The major fragmentation pathways of the protonated CP and IF are elimination of ethylene from C5 and C6 of 1,3,2-oxazaphosphorine-2-oxide via a McLafferty rearrangement, and cleavage of the P-N bond. However, their activated 4-OOH and 4-OH metabolites primarily underwent hydrogen peroxide elimination and dehydration, respectively, followed by fragmentation pathways similar to those of CP and IF. These results should prove useful in structural elucidation of future analogs of CP and IF, and/or of their metabolites. Copyright (c) 2005 John Wiley & Sons, Ltd.

Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

PubMed Central

Safe, S

1993-01-01

Polychlorinated biphenyls (PCBs) are industrial compounds that have been detected as contaminants in almost every component of the global ecosystem including the air, water, sediments, fish, and wildlife and human adipose tissue, milk, and serum. PCBs in commercial products and environmental extracts are complex mixtures of isomers and congeners that can now be analyzed on a congener-specific basis using high-resolution gas chromatographic analysis. PCBs are metabolized primarily via mixed-function oxidases into a broad spectrum of metabolites. The results indicate that metabolic activation is not required for PCB toxicity, and the parent hydrocarbons are responsible for most of the biochemical and toxic responses elicited by these compounds. Some of these responses include developmental and reproductive toxicity, dermal toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the induction of diverse phase I and phase II drug-metabolizing enzymes. Many of the effects observed for the commercial PCBs are similar to those reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Structure-function relationships for PCB congeners have identified two major structural classes of PCBs that elicit "TCDD-like" responses, namely, the coplanar PCBs (e.g., 3,3',4,4'-tetraCB, 3,3'4,4',5-pentaCB and 3,3',4,4',5,5'-hexaCB) and their mono-ortho coplanar derivatives. These compounds competitively bind to the TCDD or aryl hydrocarbon (Ah) receptor and exhibit Ah receptor agonist activity. In addition, other structural classes of PCBs elicit biochemical and toxic responses that are not mediated through the Ah receptor. The shor-term effects of PCBs on occupationally exposed humans appear to be reversible, and no consistent changes in overall mortality and cancer mortality have been reported. Recent studies have demonstrated that some developmental deficits in infants and children correlated with in utero exposure to PCBs; however, the etiologic agent(s) or structural class of PCBs responsible for these effects have not been delineated. In contrast, based on a toxic equivalency factor approach, the reproductive and developmental problems in certain wildlife populations appear to be related to the TCDD-like PCB congeners. PMID:8354174

Multisensory integration in the basal ganglia.

PubMed

Nagy, Attila; Eördegh, Gabriella; Paróczy, Zsuzsanna; Márkus, Zita; Benedek, György

2006-08-01

Sensorimotor co-ordination in mammals is achieved predominantly via the activity of the basal ganglia. To investigate the underlying multisensory information processing, we recorded the neuronal responses in the caudate nucleus (CN) and substantia nigra (SN) of anaesthetized cats to visual, auditory or somatosensory stimulation alone and also to their combinations, i.e. multisensory stimuli. The main goal of the study was to ascertain whether multisensory information provides more information to the neurons than do the individual sensory components. A majority of the investigated SN and CN multisensory units exhibited significant cross-modal interactions. The multisensory response enhancements were either additive or superadditive; multisensory response depressions were also detected. CN and SN cells with facilitatory and inhibitory interactions were found in each multisensory combination. The strengths of the multisensory interactions did not differ in the two structures. A significant inverse correlation was found between the strengths of the best unimodal responses and the magnitudes of the multisensory response enhancements, i.e. the neurons with the weakest net unimodal responses exhibited the strongest enhancement effects. The onset latencies of the responses of the integrative CN and SN neurons to the multisensory stimuli were significantly shorter than those to the unimodal stimuli. These results provide evidence that the multisensory CN and SN neurons, similarly to those in the superior colliculus and related structures, have the ability to integrate multisensory information. Multisensory integration may help in the effective processing of sensory events and the changes in the environment during motor actions controlled by the basal ganglia.

Biochemical factors modulating female genital sexual arousal physiology.

PubMed

Traish, Abdulmaged M; Botchevar, Ella; Kim, Noel N

2010-09-01

Female genital sexual arousal responses are complex neurophysiological processes consisting of central and peripheral components that occur following sexual stimulation. The peripheral responses in sexual arousal include genital vasocongestion, engorgement and lubrication resulting from a surge of vaginal and clitoral blood flow. These hemodynamic events are mediated by a host of neurotransmitters and vasoactive agents. To discuss the role of various biochemical factors modulating female genital sexual arousal responses. A comprehensive literature review was conducted using the PubMed database and citations were selected, based on topical relevance, and examined for study methodology and major findings. Data from peer-reviewed publications. Adrenergic as well as non-adrenergic non-cholinergic neurotransmitters play an important role in regulating genital physiological responses by mediating vascular and non-vascular smooth muscle contractility. Vasoactive peptides and neuropeptides also modulate genital sexual responses by regulating vascular and non-vascular smooth muscle cells and epithelial function. The endocrine milieu, particularly sex steroid hormones, is critical in the maintenance of tissue structure and function. Reduced levels of estrogens and androgen are associated with dramatic alterations in genital tissue structure, including the nerve network, as well as the response to physiological modulators. Furthermore, estrogen and androgen deficiency is associated with reduced expression of sex steroid receptors and most importantly with attenuated genital blood flow and lubrication in response to pelvic nerve stimulation. This article provides an integrated framework describing the physiological and molecular basis of various pathophysiological conditions associated with female genital sexual arousal dysfunction. © 2010 International Society for Sexual Medicine.

Federal charters for energy corporations: selected materials. Prepared at the request of Henry M. Jackson, Chairman, Committee on Interior and Insular Affairs, United States Senate, Ninety-Third Congress, Second Session, pursuant to S. Res. 45, a national fuels and energy policy study

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

None

1974-01-01

The requirement of Federal charters for large energy corporations, coupled with the appointment of public directors to serve on their boards, would make these corporations more responsive to the public interest. The large oil companies wield economic power greater than many governments by running vast production and refinery complexes, operating large tanker fleets, investing billions in resource development, and lastly, controlling the prices consumers pay for energy. Other alternatives for making the companies more responsive to public interest are to nationalize segments of the oil industry; create new federally owned oil companies; break major oil companies into functional components and/ormore » regional components; bring major oil companies under a Federal regulatory structure that treats the corporation as public utilities, regulates rates on a cost of service basis, and makes them subject to control; or improve corporate accountability and responsibility by revising the hundreds of Federal statutes that now affect various aspects of corporate practice. A collection of relevant papers are included. (MCW)« less

Mechanical Anisotropy of Rat Aortic Smooth Muscle Cells Decreases with Their Contraction

NASA Astrophysics Data System (ADS)

Nagayama, Kazuaki; Matsumoto, Takeo

Tensile properties of smooth muscle cells freshly isolated from rat thoracic aortas (FSMCs) in their major and minor axes were measured using a laboratory-made micro tensile tester. The relationship between the tension applied to a cell and its elongation was obtained in untreated cells and those treated with 10-5M serotonin to induce contraction. An initial stiffness of untreated FSMCs, normalized by their initial cross-sectional area perpendicular to the stretch direction, was significantly higher in the major axis (14.8±4.3kPa, mean±SEM, n=5) than the minor axis (2.8±1.0kPa, n=5). The stiffness increased significantly in response to the contraction, but the increase was much higher in the minor axis (59.0±9.4kPa, n=4) than in the major (88.1±13.3kPa, n=4). The difference between the two directions was insignificant in the contracted state. Observations of the morphology of actin filaments with a confocal laser scanning microscope in untreated FSMCs revealed that they were long fibers running almost parallel to the major axis, while those in contracted cells showed an aggregated structure without a preferential direction. These results may indicate that anisotropy in untreated FSMCs is caused by the anisotropic alignment of their actin filaments, and that such anisotropy disappears in response to actin filament reorganization caused by the contraction.

Crystal structure of the human glucose transporter GLUT1

NASA Astrophysics Data System (ADS)

Deng, Dong; Xu, Chao; Sun, Pengcheng; Wu, Jianping; Yan, Chuangye; Hu, Mingxu; Yan, Nieng

2014-06-01

The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 Å resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.

A single molecule study of G-quadruplex and short duplex DNA structures

NASA Astrophysics Data System (ADS)

Roy, William A., Jr.

Given that certain conditions are met, a single stranded DNA/RNA (ssDNA/RNA) structure called G-quadruplex (GQ) can form in regions throughout the genome, including at the telomeres and internal regions of the chromosomes. These structures serve various functions depending on the region in which they form which include protecting the chromosome ends, interfering with telomere elongation in cancer cells, and regulating transcription and translation level gene expression. Due to their high stability, various cellular mechanisms, such as GQ destabilizing proteins, are employed to unfold these structures during DNA replication or repair. Yet, their distinct layered structure has made GQs an attractive drug target in cancer treatment as GQ stabilizing molecules could inhibit telomerase dependent telomere elongation, a mechanism occurring in the majority of cancer cells to avoid senescence and apoptosis. However, proteins or small molecules interact with GQ that is under the influence of various cellular tension mechanisms, including the tension applied by other nearby molecules or the tension due to DNA structure within the chromatin context. Therefore, it is important to characterize the stability of various GQs and their response to interacting molecules when subjected to a tensile force. We employed a novel DNA-based nano tension generator that utilizes the elastic properties of circularized short double-stranded DNA (dsDNA) oligonucleotides to apply tension on the GQ. Since this is a completely new approach, the majority of this thesis was dedicated to proof-of-principle studies that demonstrated the feasibility and functionality of the method.

Psychotherapy for Major Depressive Disorder and Generalized Anxiety Disorder: A Health Technology Assessment.

PubMed

2017-01-01

Major depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in Canada; both are associated with a high societal and economic burden. Treatment for major depressive disorder and generalized anxiety disorder consists of pharmacological and psychological interventions. Three commonly used psychological interventions are cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The objectives of this report were to assess the effectiveness and safety of these types of therapy for the treatment of adults with major depressive disorder and/or generalized anxiety disorder, to assess the cost-effectiveness of structured psychotherapy (CBT or interpersonal therapy), to calculate the budget impact of publicly funding structured psychotherapy, and to gain a greater understanding of the experiences of people with major depressive disorder and/or generalized anxiety disorder. We performed a literature search on October 27, 2016, for systematic reviews that compared CBT, interpersonal therapy, or supportive therapy with usual care, waitlist control, or pharmacotherapy in adult outpatients with major depressive disorder and/or generalized anxiety disorder. We developed an individual-level state-transition probabilistic model for a cohort of adult outpatients aged 18 to 75 years with a primary diagnosis of major depressive disorder to determine the cost-effectiveness of individual or group CBT (as a representative form of structured psychotherapy) versus usual care. We also estimated the 5-year budget impact of publicly funding structured psychotherapy in Ontario. Finally, we interviewed people with major depressive disorder and/or generalized anxiety disorder to better understand the impact of their condition on their daily lives and their experience with different treatment options, including psychotherapy. Interpersonal therapy compared with usual care reduced posttreatment major depressive disorder scores (standardized mean difference [SMD]: 0.24, 95% confidence interval [CI]: -0.47 to -0.02) and reduced relapse/recurrence in patients with major depressive disorder (relative risk [RR]: 0.41, 95% CI: 0.27-0.63). Supportive therapy compared with usual care improved major depressive disorder scores (SMD: 0.58, 95% CI: 0.45-0.72) and increased posttreatment recovery (odds ratio [OR]: 2.71, 95% CI: 1.19-6.16) in patients with major depressive disorder. CBT compared with usual care increased response (OR: 1.58, 95% CI: 1.11-2.26) and recovery (OR: 3.42, 95% CI: 1.98-5.93) in patients with major depressive disorder and decreased relapse/recurrence (RR: 0.68, 95% CI: 0.65-0.87]). For patients with generalized anxiety disorder, CBT improved symptoms posttreatment (SMD: 0.80, 95% CI: 0.67-0.93), improved clinical response posttreatment (RR: 0.64, 95% CI: 0.55-0.74), and improved quality-of-life scores (SMD: 0.44, 95% CI: 0.06-0.82). There was a significant difference in posttreatment recovery (OR: 1.98, 95% CI: 1.11-3.54) and mean major depressive disorder symptom scores (weighted mean difference: -3.07, 95% CI: -4.69 to -1.45) for patients who received individual versus group CBT. Details about the providers of psychotherapy were rarely reported in the systematic reviews we examined.In the base case probabilistic cost-utility analysis, compared with usual care, both group and individual CBT were associated with increased survival: 0.11 quality-adjusted life-years (QALYs) (95% credible interval [CrI]: 0.03-0.22) and 0.12 QALYs (95% CrI: 0.03-0.25), respectively.Group CBT provided by nonphysicians was associated with the smallest increase in discounted costs: $401 (95% CrI: $1,177 to 1,665). Group CBT provided by physicians, individual CBT provided by nonphysicians, and individual CBT provided by physicians were associated with the incremental costs of $1,805 (95% CrI: 65-3,516), $3,168 (95% CrI: 889-5,624), and $5,311 (95% CrI: 2,539-8,938), respectively. The corresponding incremental cost-effectiveness ratio (ICER) was lowest for group CBT provided by nonphysicians ($3,715/QALY gained) and highest for individual CBT provided by physicians ($43,443/QALY gained). In the analysis that ranked best strategies, individual CBT versus group CBT provided by nonphysicians yielded an ICER of $192,618 per QALY. The probability of group CBT provided by nonphysicians being cost-effective versus usual care was greater than 95% for all willingness-to-pay thresholds over $20,000 per QALY and was around 88% for individual CBT provided by physicians at a threshold of $100,000 per QALY.We estimated that adding structured psychotherapy to usual care over the next 5 years would result in a net budget impact of $68 million to $529 million, depending on a range of factors. We also estimated that to provide structured psychotherapy to all adults with major depressive disorder (alone or combined with generalized anxiety disorder) in Ontario by 2021, an estimated 500 therapists would be needed to provide group therapy, and 2,934 therapists would be needed to provide individual therapy.People with major depressive disorder and/or generalized anxiety disorder with whom we spoke reported finding psychotherapy effective, but they also reported experiencing a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. Participants reported wanting more freedom to choose the type of psychotherapy they received. Compared with usual care, treatment with CBT, interpersonal therapy, or supportive therapy significantly reduces depression symptoms posttreatment. CBT significantly reduces anxiety symptoms posttreatment in patients with generalized anxiety disorder.Compared with usual care, treatment with structured psychotherapy (CBT or interpersonal therapy) represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder. The most affordable option is group structured psychotherapy provided by nonphysicians, with the selective use of individual structured psychotherapy provided by nonphysicians or physicians for those who would benefit most from it (i.e., patients who are not engaging well with or adhering to group therapy).

Autoimmunity-Basics and link with periodontal disease.

PubMed

Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali

2017-01-01

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Responsibility and burden from the perspective of seniors’ family caregivers: a qualitative study in Shanghai, China

PubMed Central

Zeng, Li; Zhu, Xiaoping; Meng, Xianmei; Mao, Yafen; Wu, Qian; Shi, Yan; Zhou, Lanshu

2014-01-01

Objectives: This study aimed to explore the experience of seniors’ family caregivers with regarding the responsibility, burden and support needs during caregiving in Shanghai, China. Materials and methods: An exploratory, descriptive, qualitative design was used and a semi-structure interview was conducted. A convenience sample of 11 participants in two community service centers in Shanghai was recruited. Data saturation guided the size of the sample. The Colaizzi method of empirical phenomenology was used for interviewing and analyzing data obtained from 11 caregivers. Results: Three major themes were found: It is a hard work; It is my responsibility; Social support is not enough. Conclusion: The findings of the study are practical and helpful for health care providers to develop appropriate caregiver support services, to balance the responsibility and burden of caregivers, and to consider the factors influencing the utility of support services. PMID:25126186

Stratigraphic and structural evolution of the Selenga Delta Accommodation Zone, Lake Baikal Rift, Siberia

NASA Astrophysics Data System (ADS)

Scholz, C. A.; Hutchinson, D. R.

Seismic reflection profiles from the Lake Baikal Rift reveal extensive details about the sediment thickness, structural geometry and history of extensional deformation and syn-rift sedimentation in this classic continental rift. The Selenga River is the largest single source of terrigenous input into Lake Baikal, and its large delta sits astride the major accommodation zone between the Central and South basins of the lake. Incorporating one of the world's largest lacustrine deltas, this depositional system is a classic example of the influence of rift basin structural segmentation on a major continental drainage. More than 3700km of deep basin-scale multi-channel seismic reflection (MCS) data were acquired during the 1989 Russian and the 1992 Russian-American field programs. The seismic data image most of the sedimentary section, including pre-rift basement in several localities. The MCS data reveal that the broad bathymetric saddle between these two major half-graben basins is underlain by a complex of severely deformed basement blocks, and is not simply a consequence of long-term deltaic deposition. Maximum sediment thickness is estimated to be more than 9km in some areas around the Selenga Delta. Detailed stratigraphic analyses of the Selenga area MCS data suggest that modes of deposition have shifted markedly during the history of the delta. The present mode of gravity- and mass-flow sedimentation that dominates the northern and southern parts of the modern delta, as well as the pronounced bathymetric relief in the area, are relatively recent developments in the history of the Lake Baikal Rift. Several episodes of major delta progradation, each extending far across the modern rift, can be documented in the MCS data. The stratigraphic framework defined by these prograding deltaic sequences can be used to constrain the structural as well as depositional evolution of this part of the Baikal Rift. An age model has been established for this stratigraphy, by tying the delta sequences to the site of the Baikal Drilling Project 1993 Drill Hole. Although the drill hole is only 100m deep, and the base of the cores is only 670ka in age, ages were extrapolated to deeper stratigraphic intervals using the Reflection-Seismic-Radiocarbon method of Cohen et al. (1993). The deep prograding delta sequences now observed in the MCS data probably formed in response to major fluctuations in sediment supply, rather than in response to shifts in lake level. This stratigraphic framework and age model suggest that the deep delta packages developed at intervals of approximately 400ka and may have formed as a consequence of climate changes affiliated with the northern hemisphere glaciations. The stratigraphic analysis also suggests that the Selenga Basin and Syncline developed as a distinct depocentre only during the past 2-3Ma.

Realized niches explain spatial gradients in seasonal abundance of phytoplankton groups in the South China Sea

NASA Astrophysics Data System (ADS)

Xiao, Wupeng; Wang, Lei; Laws, Edward; Xie, Yuyuan; Chen, Jixin; Liu, Xin; Chen, Bingzhang; Huang, Bangqin

2018-03-01

A basic albeit elusive goal of ocean science is to predict the structure of biological communities from the multitude of environmental conditions they experience. Estimates of the realized niche-based traits (realized traits) of phytoplankton species or functional groups in temperate seas have shown that response traits can help reveal the mechanisms responsible for structuring phytoplankton communities, but such approaches have not been tested in tropical and subtropical marginal seas. Here, we used decadal-scale studies of pigment-based phytoplankton groups and environmental conditions in the South China Sea to test whether realized traits could explain the biogeographic patterns of phytoplankton variability. We estimated the mean and breadth of the phytoplankton realized niches based on responses of the group-specific phytoplankton composition to key environmental factors, and we showed that variations of major phytoplankton groups in this system can be explained by different adaptive trade-offs to constraints imposed by temperature, irradiance, and nutrient concentrations. Differences in the patterns of trade-offs clearly separated the dominant groups from one another and generated four sets of realized traits that mirrored the observed biogeographic distribution patterns. The phytoplankton realized niches and their associated traits that we characterized in the present study could help to predict responses of phytoplankton to changes in environmental conditions in the South China Sea and could be incorporated into global biogeochemical models to anticipate shifts in community structure under future climate scenarios.

Predicting climate-driven regime shifts versus rebound potential in coral reefs.

PubMed

Graham, Nicholas A J; Jennings, Simon; MacNeil, M Aaron; Mouillot, David; Wilson, Shaun K

2015-02-05

Climate-induced coral bleaching is among the greatest current threats to coral reefs, causing widespread loss of live coral cover. Conditions under which reefs bounce back from bleaching events or shift from coral to algal dominance are unknown, making it difficult to predict and plan for differing reef responses under climate change. Here we document and predict long-term reef responses to a major climate-induced coral bleaching event that caused unprecedented region-wide mortality of Indo-Pacific corals. Following loss of >90% live coral cover, 12 of 21 reefs recovered towards pre-disturbance live coral states, while nine reefs underwent regime shifts to fleshy macroalgae. Functional diversity of associated reef fish communities shifted substantially following bleaching, returning towards pre-disturbance structure on recovering reefs, while becoming progressively altered on regime shifting reefs. We identified threshold values for a range of factors that accurately predicted ecosystem response to the bleaching event. Recovery was favoured when reefs were structurally complex and in deeper water, when density of juvenile corals and herbivorous fishes was relatively high and when nutrient loads were low. Whether reefs were inside no-take marine reserves had no bearing on ecosystem trajectory. Although conditions governing regime shift or recovery dynamics were diverse, pre-disturbance quantification of simple factors such as structural complexity and water depth accurately predicted ecosystem trajectories. These findings foreshadow the likely divergent but predictable outcomes for reef ecosystems in response to climate change, thus guiding improved management and adaptation.

Ion-Neutral Coupling in Solar Prominence

NASA Technical Reports Server (NTRS)

Gilbert, H.; DeVore, C. R.; Karpen, J.; Kucera, T.; Antiochos, S.; Kawashima, R.

2011-01-01

Coupling between ions and neutrals in magnetized plasmas is fundamentally important to many aspects of heliophysics, including our ionosphere, the solar chromosphere, the solar wind interaction with planetary atmospheres, and the interface between the heliosphere and the interstellar medium. Ion-neutral coupling also plays a major role in the physics of solar prominences. By combining theory, modeling, and observations we are working toward a better understanding of the structure and dynamics of partially ionized prominence plasma. Two key questions are addressed in the present work: 1) what physical mechanism(s) sets the cross-field scale of prominence threads? 2) Are ion-neutral interactions responsible for the vertical flows and structure in prominences? We present initial results from a study investigating what role ion-neutral interactions play in prominence dynamics and structure. This research was supported by NASA.

Differential regulation of polysaccharide-specific antibody responses to isolated polysaccharides, conjugate vaccines, and intact Gram-positive versus Gram-negative extracellular bacteria.

PubMed

Snapper, Clifford M

2016-06-24

Bacterial capsular polysaccharides are major virulence factors and are key targets in a number of licensed anti-bacterial vaccines. Their major characteristics are their large molecular weight and expression of repeating antigenic epitopes that mediate multivalent B cell receptor cross-linking. In addition, since the majority of these antigens cannot associate with MHC-II they fail to recruit CD4+ T cell help and are referred to as T cell-independent antigens. In this review I will discuss a series of studies from my laboratory that have underscored the importance of understanding polysaccharide-specific antibody responses within the context in which the PS is expressed (i.e. in isolation, as a component of conjugate vaccines, and expressed naturally by intact bacteria). We have shown that multivalent B cell receptor crosslinking, as mediated by polysaccharides, uniquely determines the qualitative response of the B cell to subsequent stimuli, but by itself is insufficient to induce antibody secretion or class switching. For these latter events to occur, second signals must act in concert with primary signals derived from the B cell receptor. The co-expression of polysaccharide and protein within intact bacteria promotes recruitment of CD4+ T cell help for the associated PS-specific IgG response, in contrast to isolated polysaccharides. Further, the particulate nature of extracellular bacteria confers properties to the polysaccharide-specific IgG response that makes it distinct immunologically from soluble conjugate vaccines. Finally, the underlying biochemical and/or structural differences that distinguish Gram-positive and Gram-negative bacteria appear to play critical roles in differentially regulating the associated polysaccharide-specific IgG responses to these groups of pathogens. These studies have a number of implications for the understanding and future design of polysaccharide-based vaccines. Published by Elsevier Ltd.

Ecosystem size structure response to 21st century climate projection: large fish abundance decreases in the central North Pacific and increases in the California Current.

PubMed

Woodworth-Jefcoats, Phoebe A; Polovina, Jeffrey J; Dunne, John P; Blanchard, Julia L

2013-03-01

Output from an earth system model is paired with a size-based food web model to investigate the effects of climate change on the abundance of large fish over the 21st century. The earth system model, forced by the Intergovernmental Panel on Climate Change (IPCC) Special report on emission scenario A2, combines a coupled climate model with a biogeochemical model including major nutrients, three phytoplankton functional groups, and zooplankton grazing. The size-based food web model includes linkages between two size-structured pelagic communities: primary producers and consumers. Our investigation focuses on seven sites in the North Pacific, each highlighting a specific aspect of projected climate change, and includes top-down ecosystem depletion through fishing. We project declines in large fish abundance ranging from 0 to 75.8% in the central North Pacific and increases of up to 43.0% in the California Current (CC) region over the 21st century in response to change in phytoplankton size structure and direct physiological effects. We find that fish abundance is especially sensitive to projected changes in large phytoplankton density and our model projects changes in the abundance of large fish being of the same order of magnitude as changes in the abundance of large phytoplankton. Thus, studies that address only climate-induced impacts to primary production without including changes to phytoplankton size structure may not adequately project ecosystem responses. © 2012 Blackwell Publishing Ltd.

Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design

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

Miao, Yi; Tenor, Jennifer L.; Toffaletti, Dena L.

ABSTRACT The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in complex with substrates or substrate analogues. The overall structures of Tps1 fromCandida albicansandAspergillus fumigatusare essentially identical and reveal N- and C-terminal Rossmann fold domains that form the glucose-6-phosphate and UDP-glucose substrate binding sites, respectively. These Tps1 structures with substrates or substrate analogues reveal key residues involved in recognition and catalysis. Disruption of these key residues severely impaired Tps1 enzymatic activity. Subsequent cellularmore » analyses also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha transition, and biofilm development. These results suggest that Tps1 enzymatic functionality is essential for the fungal stress response and virulence. Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor, validoxylamine A, visualize the transition state and support an internal return-like catalytic mechanism that is generalizable to other GT-B-fold retaining glycosyltransferases. Collectively, our results depict key Tps1-substrate interactions, unveil the enzymatic mechanism of these fungal proteins, and pave the way for high-throughput inhibitor screening buttressed and guided by the current structures and those of high-affinity ligand-Tps1 complexes. IMPORTANCEInvasive fungal diseases have emerged as major threats, resulting in more than 1.5 million deaths annually worldwide. This epidemic has been further complicated by increasing resistance to all major classes of antifungal drugs in the clinic. Trehalose biosynthesis is essential for the fungal stress response and virulence. Critically, this biosynthetic pathway is absent in mammals, and thus, the two enzymes that carry out trehalose biosynthesis, namely, trehalose-6-phosphate synthase (Tps1) and trehalose-6-phosphate phosphatase (Tps2), are prominent targets for antifungal intervention. Here, we report the first eukaryotic Tps1 structures from the pathogenic fungiCandida albicansandAspergillus fumigatusin complex with substrates, substrate analogues, and inhibitors. These structures reveal key protein-substrate interactions, providing atomic-level scaffolds for structure-guided drug design of novel antifungals that target Tps1.« less

Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design.

PubMed

Miao, Yi; Tenor, Jennifer L; Toffaletti, Dena L; Maskarinec, Stacey A; Liu, Jiuyu; Lee, Richard E; Perfect, John R; Brennan, Richard G

2017-07-25

The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in complex with substrates or substrate analogues. The overall structures of Tps1 from Candida albicans and Aspergillus fumigatus are essentially identical and reveal N- and C-terminal Rossmann fold domains that form the glucose-6-phosphate and UDP-glucose substrate binding sites, respectively. These Tps1 structures with substrates or substrate analogues reveal key residues involved in recognition and catalysis. Disruption of these key residues severely impaired Tps1 enzymatic activity. Subsequent cellular analyses also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha transition, and biofilm development. These results suggest that Tps1 enzymatic functionality is essential for the fungal stress response and virulence. Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor, validoxylamine A, visualize the transition state and support an internal return-like catalytic mechanism that is generalizable to other GT-B-fold retaining glycosyltransferases. Collectively, our results depict key Tps1-substrate interactions, unveil the enzymatic mechanism of these fungal proteins, and pave the way for high-throughput inhibitor screening buttressed and guided by the current structures and those of high-affinity ligand-Tps1 complexes. IMPORTANCE Invasive fungal diseases have emerged as major threats, resulting in more than 1.5 million deaths annually worldwide. This epidemic has been further complicated by increasing resistance to all major classes of antifungal drugs in the clinic. Trehalose biosynthesis is essential for the fungal stress response and virulence. Critically, this biosynthetic pathway is absent in mammals, and thus, the two enzymes that carry out trehalose biosynthesis, namely, trehalose-6-phosphate synthase (Tps1) and trehalose-6-phosphate phosphatase (Tps2), are prominent targets for antifungal intervention. Here, we report the first eukaryotic Tps1 structures from the pathogenic fungi Candida albicans and Aspergillus fumigatus in complex with substrates, substrate analogues, and inhibitors. These structures reveal key protein-substrate interactions, providing atomic-level scaffolds for structure-guided drug design of novel antifungals that target Tps1. Copyright © 2017 Miao et al.

Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function.

PubMed

Oltedal, Leif; Kessler, Ute; Ersland, Lars; Grüner, Renate; Andreassen, Ole A; Haavik, Jan; Hoff, Per Ivar; Hammar, Åsa; Dale, Anders M; Hugdahl, Kenneth; Oedegaard, Ketil J

2015-05-01

Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented. The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT. n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months. The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

The chaos of hospitalisation for patients with Critical Limb Ischaemia approaching major amputation.

PubMed

Monaro, Susan; West, Sandra; Pinkova, Jana; Gullick, Janice

2018-05-18

To illuminate the hospital experience for patients and families when major amputation has been advised for critical limb ischaemia (CLI). CLI creates significant burden to the health system and the family, particularly as the person with CLI approaches amputation. Major amputation is often offered as a late intervention for CLI in response to the marked deterioration of an ischaemic limb, and functional decline from reduced mobility, intractable pain, infection and/or toxaemia. While a wealth of clinical outcome data on CLI and amputation exists internationally, little is known about the patient/ family-centred experience of hospitalisation to inform preservation of personhood and patient-centred care-planning. Longitudinal qualitative study using Heideggerian Phenomenology. 14 patients and 13 family carers provided a semi-structured interview after advice for major amputation. Where amputation followed, a second interview (6-months post-procedure) was provided by eight patients and seven family carers. Forty-two semi-structured interviews were audio-recorded and transcribed verbatim. Hermeneutic phenomenological analysis followed. Hospitalisation for CLI, with or without amputation, created a sense of chaos, characterised by being fragile and needing more time for care (fragile body and fragile mind, nurse busyness, and carer hyper-vigilance), being adrift within uncontrollable spaces (noise, unreliable space, precarious accommodation and unpredictable scheduling), and being confused by missed and mixed messages (multiple stakeholders, information overload, and cultural/linguistic diversity). Patients and families need a range of strategies to assist mindful decision-making in preparation for amputation in what for them is a chaotic process occurring within a chaotic environment. Cognitive deficits increase the care complexity and burden of family advocacy. A co-ordinated, interprofessional response should improve systems for communication, family engagement, operation scheduling and discharge-planning to support preparation, adjustment and allow a sense of safety to develop. Formal peer-support for patients and caregivers should be actively facilitated. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Isolation and characterization of major histocompatibility complex class IIB genes from the nurse shark.

PubMed

Bartl, S; Weissman, I L

1994-01-04

The major histocompatibility complex (MHC) contains a set of linked genes which encode cell surface proteins involved in the binding of small peptide antigens for their subsequent recognition by T lymphocytes. MHC proteins share structural features and the presence and location of polymorphic residues which play a role in the binding of antigens. In order to compare the structure of these molecules and gain insights into their evolution, we have isolated two MHC class IIB genes from the nurse shark, Ginglymostoma cirratum. Two clones, most probably alleles, encode proteins which differ by 13 amino acids located in the putative antigen-binding cleft. The protein structure and the location of polymorphic residues are similar to their mammalian counterparts. Although these genes appear to encode a typical MHC protein, no T-cell-mediated responses have been demonstrated in cartilaginous fish. The nurse shark represents the most phylogenetically primitive organism in which both class IIA [Kasahara, M., Vazquez, M., Sato, K., McKinney, E.C. & Flajnik, M.F. (1992) Proc. Natl. Acad. Sci USA 89, 6688-6692] and class IIB genes, presumably encoding the alpha/beta heterodimer, have been isolated.

GlycomeDB – integration of open-access carbohydrate structure databases

PubMed Central

Ranzinger, René; Herget, Stephan; Wetter, Thomas; von der Lieth, Claus-Wilhelm

2008-01-01

Background Although carbohydrates are the third major class of biological macromolecules, after proteins and DNA, there is neither a comprehensive database for carbohydrate structures nor an established universal structure encoding scheme for computational purposes. Funding for further development of the Complex Carbohydrate Structure Database (CCSD or CarbBank) ceased in 1997, and since then several initiatives have developed independent databases with partially overlapping foci. For each database, different encoding schemes for residues and sequence topology were designed. Therefore, it is virtually impossible to obtain an overview of all deposited structures or to compare the contents of the various databases. Results We have implemented procedures which download the structures contained in the seven major databases, e.g. GLYCOSCIENCES.de, the Consortium for Functional Glycomics (CFG), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Bacterial Carbohydrate Structure Database (BCSDB). We have created a new database called GlycomeDB, containing all structures, their taxonomic annotations and references (IDs) for the original databases. More than 100000 datasets were imported, resulting in more than 33000 unique sequences now encoded in GlycomeDB using the universal format GlycoCT. Inconsistencies were found in all public databases, which were discussed and corrected in multiple feedback rounds with the responsible curators. Conclusion GlycomeDB is a new, publicly available database for carbohydrate sequences with a unified, all-encompassing structure encoding format and NCBI taxonomic referencing. The database is updated weekly and can be downloaded free of charge. The JAVA application GlycoUpdateDB is also available for establishing and updating a local installation of GlycomeDB. With the advent of GlycomeDB, the distributed islands of knowledge in glycomics are now bridged to form a single resource. PMID:18803830

A Comparison of Aircraft Maintenance Organizational Structures

DTIC Science & Technology

1992-09-01

Outputs ... ...................... 85 Appendix E : Double Cross-Validation ........... 117 Appendix F: Exchange of Independent Variables...splits into three major production branches (6). See Figure 8. 26 Aircraf t Interm ia•’ e Maintenance Off icerzI A ssistantAIKO I 1|A/ant a A Traiing...responsible for all aircraft maintenance activities, see Figure 9 (4:3). rdor ! E •; e Techn•1i Se~rvices Wff oE r I f .1 Bass Airaraf t Iaintenanoc E

A preliminary study of the tropical water cycle and its sensitivity to surface warming

NASA Technical Reports Server (NTRS)

Lau, K. M.; Sui, C. H.; Tao, W. K.

1993-01-01

The Goddard Cumulus Ensemble Model (GCEM) has been used to demonstrate that cumulus-scale dynamics and microphysics play a major role in determining the vertical distribution of water vapor and clouds in the tropical atmosphere. The GCEM is described and is the basic structure of cumulus convection. The long-term equilibrium response to tropical convection to surface warming is examined. A picture of the water cycle within tropical cumulus clusters is developed.

Comparative Analysis of Immediate Response by National Disaster Management Systems of the U.S., Pakistan, and Turkey

DTIC Science & Technology

2014-06-01

incremental increase in contamination and pollution, construction of unsafe structures in flood-prone areas, adverse effects of income gap and poverty...them claim that climate change, contamination , ozone depletion, and biodiversity loss are major factors, others believe that the real causes for the...the international arena, as well as the host country, while the second one has very little physical protection and is often faced with food , water

The Fpg/Nei family of DNA glycosylases: substrates, structures, and search for damage.

PubMed

Prakash, Aishwarya; Doublié, Sylvie; Wallace, Susan S

2012-01-01

During the initial stages of the base excision DNA repair pathway, DNA glycosylases are responsible for locating and removing the majority of endogenous oxidative base lesions. The bifunctional formamidopyrimidine DNA glycosylase (Fpg) and endonuclease VIII (Nei) are members of the Fpg/Nei family, one of the two families of glycosylases that recognize oxidized DNA bases, the other being the HhH/GPD (or Nth) superfamily. Structural and biochemical developments over the past decades have led to novel insights into the mechanism of damage recognition by the Fpg/Nei family of enzymes. Despite the overall structural similarity among members of this family, these enzymes exhibit distinct features that make them unique. This review summarizes the current structural knowledge of the Fpg/Nei family members, emphasizes their substrate specificities, and describes how these enzymes search for lesions. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling and Simulation of Offshore Wind Power Platform for 5 MW Baseline NREL Turbine.

PubMed

Roni Sahroni, Taufik

2015-01-01

This paper presents the modeling and simulation of offshore wind power platform for oil and gas companies. Wind energy has become the fastest growing renewable energy in the world and major gains in terms of energy generation are achievable when turbines are moved offshore. The objective of this project is to propose new design of an offshore wind power platform. Offshore wind turbine (OWT) is composed of three main structures comprising the rotor/blades, the tower nacelle, and the supporting structure. The modeling analysis was focused on the nacelle and supporting structure. The completed final design was analyzed using finite element modeling tool ANSYS to obtain the structure's response towards loading conditions and to ensure it complies with guidelines laid out by classification authority Det Norske Veritas. As a result, a new model of the offshore wind power platform for 5 MW Baseline NREL turbine was proposed.

Modeling and Simulation of Offshore Wind Power Platform for 5 MW Baseline NREL Turbine

PubMed Central

Roni Sahroni, Taufik

2015-01-01

This paper presents the modeling and simulation of offshore wind power platform for oil and gas companies. Wind energy has become the fastest growing renewable energy in the world and major gains in terms of energy generation are achievable when turbines are moved offshore. The objective of this project is to propose new design of an offshore wind power platform. Offshore wind turbine (OWT) is composed of three main structures comprising the rotor/blades, the tower nacelle, and the supporting structure. The modeling analysis was focused on the nacelle and supporting structure. The completed final design was analyzed using finite element modeling tool ANSYS to obtain the structure's response towards loading conditions and to ensure it complies with guidelines laid out by classification authority Det Norske Veritas. As a result, a new model of the offshore wind power platform for 5 MW Baseline NREL turbine was proposed. PMID:26550605

Atomic resolution structure of the E. coli YajR transporter YAM domain.

PubMed

Jiang, Daohua; Zhao, Yan; Fan, Junping; Liu, Xuehui; Wu, Yan; Feng, Wei; Zhang, Xuejun C

2014-07-25

YajR is an Escherichia coli transporter that belongs to the major facilitator superfamily. Unlike most MFS transporters, YajR contains a carboxyl terminal, cytosolic domain of 67 amino acid residues termed YAM domain. Although it is speculated that the function of this small soluble domain is to regulate the conformational change of the 12-helix transmembrane domain, its precise regulatory role remains unclear. Here, we report the crystal structure of the YAM domain at 1.07-Å resolution, along with its structure determined using nuclear magnetic resonance. Detailed analysis of the high resolution structure revealed a symmetrical dimer in which a belt of well-ordered poly-pentagonal water molecules is embedded. A mutagenesis experiment and a thermal stability assay were used to analyze the putative role of this dimerization in response to changes in halogen concentration. Copyright © 2014 Elsevier Inc. All rights reserved.

Biochemical Effects of six Ti02 and four Ce02 Nanomaterials ...

EPA Pesticide Factsheets

Abstract The potential mammalian hepatotoxicity of nanomaterials were explored in dose-response and structure-activity studies with human hepatic HepG2 cells exposed to between 10 and 1000 ug/ml of six different TiO2 and four CeO2 nanomaterials for 3 days. Various biochemical parameters were then evaluated to study cytotoxicity, cell growth, hepatic function and oxidative stress. Few indications of cytotoxicity were observed between 10 and 100 ug/ml. In the 300 to 1000 ug/ml exposure range a moderate to substantial degree of cytotoxicity was observed. The percent of lactic dehydrogenase released from cells was the most sensitive cytotoxicity parameter. There were four major biochemical effects observed. By far decreased activities of glucose 6-phosphate dehydrogenase was the major finding of this enzymatic study with some significant decreases observed at 10 ug/ml. In the range of 100 to 1000 ug/ml, the activities of superoxide dismutase, glutathione reductase and glutathione peroxidase were decreased by many nanomaterials. There are six factors that contribute to substantial oxidative stress in cultured hepatocytes (decreased GSH content, and reduced G6PDH, GRD, GPX, SOD and altered catalase activities). Cytotoxicity per se did not seem to fully explain the patterns of biological responses observed. With respect to structure-activity, nanomaterials of CeO2 were more effective than TiO2 in reducing glutathione reductase and SOD activ

Impact of the variation in dynamic vehicle load on flexible pavement responses

NASA Astrophysics Data System (ADS)

Ahsanuzzaman, Md

The purpose of this research was to evaluate the dynamic variation in asphalt pavement critical responses due to dynamic tire load variations. An attempt was also made to develop generalized regression equations to predict the dynamic response variation in flexible pavement under various dynamic load conditions. The study used an extensive database of computed pavement response histories for five different types of sites (smooth, rough, medium rough, very rough and severely rough), two different asphalt pavement structures (thin and thick) at two temperatures (70 °F and 104 °F), subjected to a tandem axle dual tire at three speeds 25, 37 and 50 mph (40, 60 and 80 km/h). All pavement responses were determined using the 3D-Move Analysis program (Version 1.2) developed by University of Nevada, Reno. A new term called Dynamic Response Coefficient (DRC) was introduced in this study to address the variation in critical pavement responses due to dynamic loads as traditionally measured by the Dynamic Load Coefficient (DLC). While DLC represents the additional varying component of the tire load, DRC represents the additional varying component of the response value (standard deviation divided by mean response). In this study, DRC was compared with DLC for five different sites based on the roughness condition of the sites. Previous studies showed that DLC varies with vehicle speed and suspension types, and assumes a constant value for the whole pavement structure (lateral and vertical directions). On the other hand, in this study, DRC was found to be significantly varied with the asphalt pavement and function of pavement structure, road roughness conditions, temperatures, vehicle speeds, suspension types, and locations of the point of interest in the pavement. A major contribution of the study is that the variation of pavement responses due to dynamic load in a flexible pavement system can be predicted with generalized regression equations. Fitting parameters (R2) in the rage of 0.60 to 0.87 were observed the DRC predictive equations. In addition, verification of those generalized equations was evaluated using different sets of asphalt pavement structures and pavement materials. The differences between calculated and predicted values were found to be within +/-20% for the maximum tensile strain and +/-30% for the maximum compressive strain in the asphalt layer.

The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

PubMed Central

Renault, Ilana Zalcberg; Scholl, Vanesa; Hassan, Rocio; Capelleti, Paola; de Lima, Marcos; Cortes, Jorge

2011-01-01

Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging. PMID:23049363

Optically-based Sensor System for Critical Nuclear Facilities Post-Event Seismic Structural Assessment

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

McCallen, David; Petrone, Floriana; Buckle, Ian

The U.S. Department of Energy (DOE) has ownership and operational responsibility for a large enterprise of nuclear facilities that provide essential functions to DOE missions ranging from national security to discovery science and energy research. These facilities support a number of DOE programs and offices including the National Nuclear Security Administration, Office of Science, and Office of Environmental Management. With many unique and “one of a kind” functions, these facilities represent a tremendous national investment, and assuring their safety and integrity is fundamental to the success of a breadth of DOE programs. Many DOE critical facilities are located in regionsmore » with significant natural phenomenon hazards including major earthquakes and DOE has been a leader in developing standards for the seismic analysis of nuclear facilities. Attaining and sustaining excellence in nuclear facility design and management must be a core competency of the DOE. An important part of nuclear facility management is the ability to monitor facilities and rapidly assess the response and integrity of the facilities after any major upset event. Experience in the western U.S. has shown that understanding facility integrity after a major earthquake is a significant challenge which, lacking key data, can require extensive effort and significant time. In the work described in the attached report, a transformational approach to earthquake monitoring of facilities is described and demonstrated. An entirely new type of optically-based sensor that can directly and accurately measure the earthquake-induced deformations of a critical facility has been developed and tested. This report summarizes large-scale shake table testing of the sensor concept on a representative steel frame building structure, and provides quantitative data on the accuracy of the sensor measurements.« less

Non-governmental organizational health operations in humanitarian crises: the case for technical support units.

PubMed

Greenough, P Gregg; Nazerali, Rahim; Fink, Sheri; VanRooyen, Michael J

2007-01-01

As the humanitarian health response industry grows, there is a need for technical health expertise that can build an evidence base around outcome measures and raise the quality and accountability of the health relief response. We propose the formation of technical support units (TSUs), entities of health expertise institutionalized within humanitarian non-governmental organizations (NGOs), which will bridge the gap between the demand for evidence-based, humanitarian programming and the field capacity to accomplish it. With the input of major humanitarian NGOs and donors, this paper discusses the attributes and capacities ofTSUs; and the mechanisms for creating and enhancing TSUs within the NGO management structure.

How an active-learning class influences physics self-efficacy in pre-service teachers

NASA Astrophysics Data System (ADS)

Gaffney, Jon D. H.; Housley Gaffney, Amy L.; Usher, Ellen L.; Mamaril, Natasha A.

2013-01-01

Education majors in an inquiry-based physics content course were asked to reflect on the ways the course affected their self-efficacy for completing physics tasks, such as creating a circuit. Responses were coded according to the contributor of the influence and whether that influence was positive or negative. The group learning structure, hands-on activities in the class, and the constructed repertoire of science knowledge, processes, and activities, were all reported to be positive influences on self-efficacy, whereas the influence of the instructor was mixed. Overall, students' responses indicated both a desire for more guidance and lecture and an appreciation for their ability to construct their own understanding through the class activities.

Molecular responses in root-associative rhizospheric bacteria to variations in plant exudates

NASA Astrophysics Data System (ADS)

Abdoun, Hamid; McMillan, Mary; Pereg, Lily

2015-04-01

Plant exudates are a major factor in the interface of plant-soil-microbe interactions and it is well documented that the microbial community structure in the rhizosphere is largely influenced by the particular exudates excreted by various plants. Azospirillum brasilense is a plant growth promoting rhizobacterium that is known to interact with a large number of plants, including important food crops. The regulatory gene flcA has an important role in this interaction as it controls morphological differentiation of the bacterium that is essential for attachment to root surfaces. Being a response regulatory gene, flcA mediates the response of the bacterial cell to signals from the surrounding rhizosphere. This makes this regulatory gene a good candidate for analysis of the response of bacteria to rhizospheric alterations, in this case, variations in root exudates. We will report on our studies on the response of Azospirillum, an ecologically, scientifically and agriculturally important bacterial genus, to variations in the rhizosphere.

Iranian nurses' perceptions of social responsibility: a qualitative study.

PubMed

Faseleh-Jahromi, Mohsen; Moattari, Marzieh; Peyrovi, Hamid

2014-05-01

Social responsibility is intertwined with nursing; however, perceptions of Iranian nurses about social responsibility has not been explored yet. This study, as part of a larger qualitative grounded theory approach study, aims to explore Iranian nurses' perception of social responsibility. The study participants included 10 nurses with different job levels. The study data were generated through semi-structured interviews. The participants were selected through purposeful sampling approach, which was then followed by theoretical sampling until reaching the point of data saturation. All the interviews were recorded, transcribed, and analyzed through constant comparative analysis. Positive human characteristics, professional competencies, professional values, solution-focused nursing care, and deployment of professional performance are five categories obtained from the study. The participants believed socially responsible nurses to have positive personality characteristics as well as the necessary skills to do their duties accurately. Such nurses also respect the values, observe the professional principles, and take major steps toward promotion and deployment of the nursing profession in the society.

Assessment of source of information for polio supplementary immunization activities in 2014 and 2015, Somali, Ethiopia.

PubMed

Bedada, Selamawit Yilma; Gallagher, Kathleen; Aregay, Aron Kassahun; Mohammed, Bashir; Maalin, Mohammed Adem; Hassen, Hassen Abdisemed; Ali, Yusuf Mohammed; Braka, Fiona; Kilebou, Pierre M'pele

2017-01-01

Communication is key for the successful implementation of polio vaccination campaigns. The purpose of this study is to review and analyse the sources of information utilized by caregivers during polio supplementary immunization activities (SIAs) in Somali, Ethiopia in 2014 and 2015. Data on sources of information about the polio campaign were collected post campaign from caregivers by trained data collectors as part of house to house independent monitoring. The sources of information analysed in this paper include town criers (via megaphones), health workers, religious leaders, kebele leaders (Kebele is the lowest administrative structure in Ethiopia), radio, television, text message and others. The repetition of these sources of information was analysed across years and zones for trends. Polio vaccination campaign coverage was also reviewed by year and zones within the Somali region in parallel with the major sources of information used in the respective year and zones. 57,745 responses were used for this analysis but the responses were received from < or = 57,745 individuals since some of them may provide more than one response. Moreover, because sampling of households is conducted independently during each round of independent monitoring, the same household may have been included more than once in our analysis. The methodology used for independent monitoring does not allow for the calculation of response rates. Monitors go from house to house until information from 20 households is received. From the total 57,745 responses reviewed, over 37% of respondents reported that town criers were their source for information about the 2014 and 2015 polio SIAs. Zonal trends in using town criers as a major source of information in both study years remained consistent except in two zones. 87.5% of zones that reported at least 90% coverage during both study years had utilized town criers as a major source of information while the rest (12.5%) used health workers. We found that town criers were consistently the major source of information about the polio campaigns for Somali region parents and caregivers during polio immunization days held in 2014 and 2015. Health workers and kebele leaders were also important sources of information about the polio campaign for parents.

Physicians' Migration: Perceptions of Pakistani Medical Students.

PubMed

Hossain, Nazli; Shah, Nusrat; Shah, Tahira; Lateef, Sidra Binte

2016-08-01

To study the perceptions of medical students about factors responsible for physicians'migration. Cross-sectional survey. Dow Medical College and Civil Hospital, Karachi, from April to May 2015. Aself-administered structured questionnaire was used including demographic details, attitudes about push and pull factors of migration, and reasons for migrating or not migrating abroad. Final year students and interns were included. Likert scale from 1 to 4 (1=strongly disagree to 4=strongly agree) was used to assess attitudes. Data was analyzed by SPSS version 16. Atotal of 240 medical students, mostly females (n=181, 75%) (60% final year and 40% interns), participated in the study. Majority wished to go abroad (n=127; 54%) with United States being the favourite destination (n=80; 66.1%) and internal medicine fields being the preferred choice for specialization (n=126; 54%). The major pull factors were better quality of postgraduate education abroad (n=110; 48.2%) and economic prospects (80; 35.2%); while the push factors were a weak healthcare system (n=219; 94.3%), inadequate salary structure (n=205; 88.3%), insecurity (n=219; 93.9%) and increasing religious intolerance in Pakistan (n=183; 78.5%). This survey highlights the continuing trend of physician migration from Pakistan owing to an interplay of various push and pull factors. Majority of our medical students wish to migrate, mainly due to low salaries, poor job structure, and insecurity. Urgent interventions are required to reverse this trend of medical brain-drain.

When a natural disaster occurs: lessons learned in meeting students' needs.

PubMed

Watson, Pamela G; Loffredo, Vincent J; McKee, John C

2011-01-01

Across the nation, weather-related natural disasters-tropical storms, floods, tornadoes, and earthquakes-struck even areas where weather concerns are not paramount on the minds of most people. These natural disasters heightened awareness that all geographic areas are susceptible to aberrant weather conditions. The purpose of this article was to relate the lessons learned by one academic health center in meeting students' emergency preparedness and disaster recovery needs following a major hurricane in fall 2008. To gauge students' storm-related needs, a Hurricane Needs Survey (HNS) was conducted in spring 2009, 7 months after the hurricane. Students responded to 26 structured response items and 3 open-ended questions. Five hundred fifteen surveys were completed, constituting a response rate of 37.2%. Data were analyzed by creating frequencies to profile students' hurricane experiences. Results indicated that all students left the island under mandatory evacuation orders; most stayed with their families, and most experienced moderate material losses. For some students, the evacuation process and life after the storm contributed to ongoing problems, worries, and academic performance issues. Qualitative content analysis was used to derive themes from the students' narrative responses to the HNS open-ended questions about their perceptions of the extent to which the University of Texas Medical Branch met their needs. When students' hurricane response comments were analyzed, three major themes emerged: being prepared, needing to be connected, and returning to normalcy. The major lessons learned are that the emergency preparation of students requires greater specificity and that discussion about poststorm recovery expectations is essential. Following a natural disaster, students experience more distress than may be readily apparent. Copyright © 2011 Elsevier Inc. All rights reserved.

ISAC - A tool for aeroservoelastic modeling and analysis. [Interaction of Structures, Aerodynamics, and Control

NASA Technical Reports Server (NTRS)

Adams, William M., Jr.; Hoadley, Sherwood T.

1993-01-01

This paper discusses the capabilities of the Interaction of Structures, Aerodynamics, and Controls (ISAC) system of program modules. The major modeling, analysis, and data management components of ISAC are identified. Equations of motion are displayed for a Laplace-domain representation of the unsteady aerodynamic forces. Options for approximating a frequency-domain representation of unsteady aerodynamic forces with rational functions of the Laplace variable are shown. Linear time invariant state-space equations of motion that result are discussed. Model generation and analyses of stability and dynamic response characteristics are shown for an aeroelastic vehicle which illustrate some of the capabilities of ISAC as a modeling and analysis tool for aeroelastic applications.

Rhyme generation by deaf adults.

PubMed

Hanson, V L; McGarr, N S

1989-03-01

Congenitally deaf college students were asked to generate rhymes to 50 target words. Results of the investigation indicate that it is possible for deaf individuals to develop the sensitivity to the phonologic structure of the words necessary for rhyming: Approximately half of the responses generated correct rhymes. Of these correct rhymes, the majority were orthographically similar to their target (c.g., BLUE-glue and TIE-lie), although 30% were orthographically dissimilar to their targets (e.g., BLUE-through and TIE-sky), indicating an ability to generate rhymes independent of orthographic structure. Errors were analyzed in an attempt to determine the basis on which the subjects generated rhymes. Evidence of both orthographic and speech-related strategies were obtained.

Is Cycloxygenase-2 (COX-2) a Major Component of the Mechanism Responsible for Microvascular Remodeling in the Brain?

NASA Astrophysics Data System (ADS)

LaManna, Joseph C.; Sun, Xiaoyan; Ivy, Andre D.; Ward, Nicole L.

We have used a relatively simple model of hypoxia that triggers adaptive structural changes in the cerebral microvasculature to study the process of physiological angiogenesis. This model can be used to obtain mechanistic data for the processes that probably underlie the dynamic structural changes that occur in learning and the control of oxygen availability to the neurovascular unit. These mechanisms are broadly involved in a wide variety of pathophysiological processes. This is the vascular component to CNS functional plasticity, supporting learning and adaptation. The angiogenic process may wane with age, contributing to the decreasing ability to survive metabolic stress and the diminution of neuronal plasticity.

The EMS system and disaster planning: some observations.

PubMed

Holloway, R D; Steliga, J F; Ryan, C T

1978-02-01

Disaster planning, one of the 15 essential components of the Emergency Medical Service System Act of 1973, should be the culmination of the establishment of other components. Regions have gone to varying lengths to describe disaster plans but how realistic the plans are is questionable. New York has planned for multiple casualty incidents (MCI) to care for victims of fires, explosions, structural collapses and major transportation incidents. The irrational emotional response in mass disasters conflicts with the rational disaster plans written by health planners. Drills of disaster plans are not realistic. One solution is to designate the next serious incident, such as a fire or traffic accident, a major MCI. The ability to handle an MCI is probably the best measure of an EMS system's effectiveness.

The FlyBase database of the Drosophila genome projects and community literature

PubMed Central

2003-01-01

FlyBase (http://flybase.bio.indiana.edu/) provides an integrated view of the fundamental genomic and genetic data on the major genetic model Drosophila melanogaster and related species. FlyBase has primary responsibility for the continual reannotation of the D. melanogaster genome. The ultimate goal of the reannotation effort is to decorate the euchromatic sequence of the genome with as much biological information as is available from the community and from the major genome project centers. A complete revision of the annotations of the now-finished euchromatic genomic sequence has been completed. There are many points of entry to the genome within FlyBase, most notably through maps, gene products and ontologies, structured phenotypic and gene expression data, and anatomy. PMID:12519974

Recent findings in cardiovascular physiology with space travel.

PubMed

Hughson, Richard L

2009-10-01

The cardiovascular system undergoes major changes in stress with space flight primarily related to the elimination of the head-to-foot gravitational force. A major observation has been that the central venous pressure is not elevated early in space flight yet stroke volume is increased at least early in flight. Recent observations demonstrate that heart rate remains lower during the normal daily activities of space flight compared to Earth-based conditions. Structural and functional adaptations occur in the vascular system that could result in impaired response with demands of physical exertion and return to Earth. Cardiac muscle mass is reduced after flight and contractile function may be altered. Regular and specific countermeasures are essential to maintain cardiovascular health during long-duration space flight.

Investigation of Quasi-Static Indentation Response of Inkjet Printed Sandwich Structures under Various Indenter Geometries

PubMed Central

Dikshit, Vishwesh; Nagalingam, Arun Prasanth; Yap, Yee Ling; Sing, Swee Leong; Yeong, Wai Yee; Wei, Jun

2017-01-01

The objective of this investigation was to determine the quasi-static indentation response and failure mode in three-dimensional (3D) printed trapezoidal core structures, and to characterize the energy absorbed by the structures. In this work, the trapezoidal sandwich structure was designed in the following two ways. Firstly, the trapezoidal core along with its facesheet was 3D printed as a single element comprising a single material for both core and facesheet (type A); Secondly, the trapezoidal core along with facesheet was 3D printed, but with variation in facesheet materials (type B). Quasi-static indentation was carried out using three different indenters, namely standard hemispherical, conical, and flat indenters. Acoustic emission (AE) technique was used to capture brittle cracking in the specimens during indentation. The major failure modes were found to be brittle failure and quasi-brittle fractures. The measured indentation energy was at a maximum when using a conical indenter at 9.40 J and 9.66 J and was at a minimum when using a hemispherical indenter at 6.87 J and 8.82 J for type A and type B series specimens respectively. The observed maximum indenter displacements at failure were the effect of material variations and composite configurations in the facesheet. PMID:28772649

Investigation of Quasi-Static Indentation Response of Inkjet Printed Sandwich Structures under Various Indenter Geometries.

PubMed

Dikshit, Vishwesh; Nagalingam, Arun Prasanth; Yap, Yee Ling; Sing, Swee Leong; Yeong, Wai Yee; Wei, Jun

2017-03-14

The objective of this investigation was to determine the quasi-static indentation response and failure mode in three-dimensional (3D) printed trapezoidal core structures, and to characterize the energy absorbed by the structures. In this work, the trapezoidal sandwich structure was designed in the following two ways. Firstly, the trapezoidal core along with its facesheet was 3D printed as a single element comprising a single material for both core and facesheet (type A); Secondly, the trapezoidal core along with facesheet was 3D printed, but with variation in facesheet materials (type B). Quasi-static indentation was carried out using three different indenters, namely standard hemispherical, conical, and flat indenters. Acoustic emission (AE) technique was used to capture brittle cracking in the specimens during indentation. The major failure modes were found to be brittle failure and quasi-brittle fractures. The measured indentation energy was at a maximum when using a conical indenter at 9.40 J and 9.66 J and was at a minimum when using a hemispherical indenter at 6.87 J and 8.82 J for type A and type B series specimens respectively. The observed maximum indenter displacements at failure were the effect of material variations and composite configurations in the facesheet.

Physics and evolution of thermophilic adaptation.

PubMed

Berezovsky, Igor N; Shakhnovich, Eugene I

2005-09-06

Analysis of structures and sequences of several hyperthermostable proteins from various sources reveals two major physical mechanisms of their thermostabilization. The first mechanism is "structure-based," whereby some hyperthermostable proteins are significantly more compact than their mesophilic homologues, while no particular interaction type appears to cause stabilization; rather, a sheer number of interactions is responsible for thermostability. Other hyperthermostable proteins employ an alternative, "sequence-based" mechanism of their thermal stabilization. They do not show pronounced structural differences from mesophilic homologues. Rather, a small number of apparently strong interactions is responsible for high thermal stability of these proteins. High-throughput comparative analysis of structures and complete genomes of several hyperthermophilic archaea and bacteria revealed that organisms develop diverse strategies of thermophilic adaptation by using, to a varying degree, two fundamental physical mechanisms of thermostability. The choice of a particular strategy depends on the evolutionary history of an organism. Proteins from organisms that originated in an extreme environment, such as hyperthermophilic archaea (Pyrococcus furiosus), are significantly more compact and more hydrophobic than their mesophilic counterparts. Alternatively, organisms that evolved as mesophiles but later recolonized a hot environment (Thermotoga maritima) relied in their evolutionary strategy of thermophilic adaptation on "sequence-based" mechanism of thermostability. We propose an evolutionary explanation of these differences based on physical concepts of protein designability.

Using block pulse functions for seismic vibration semi-active control of structures with MR dampers

NASA Astrophysics Data System (ADS)

Rahimi Gendeshmin, Saeed; Davarnia, Daniel

2018-03-01

This article applied the idea of block pulse functions in the semi-active control of structures. The BP functions give effective tools to approximate complex problems. The applied control algorithm has a major effect on the performance of the controlled system and the requirements of the control devices. In control problems, it is important to devise an accurate analytical technique with less computational cost. It is proved that the BP functions are fundamental tools in approximation problems which have been applied in disparate areas in last decades. This study focuses on the employment of BP functions in control algorithm concerning reduction the computational cost. Magneto-rheological (MR) dampers are one of the well-known semi-active tools that can be used to control the response of civil Structures during earthquake. For validation purposes, numerical simulations of a 5-story shear building frame with MR dampers are presented. The results of suggested method were compared with results obtained by controlling the frame by the optimal control method based on linear quadratic regulator theory. It can be seen from simulation results that the suggested method can be helpful in reducing seismic structural responses. Besides, this method has acceptable accuracy and is in agreement with optimal control method with less computational costs.

Hydro-dynamic damping theory in flowing water

NASA Astrophysics Data System (ADS)

Monette, C.; Nennemann, B.; Seeley, C.; Coutu, A.; Marmont, H.

2014-03-01

Fluid-structure interaction (FSI) has a major impact on the dynamic response of the structural components of hydroelectric turbines. On mid-head to high-head Francis runners, the rotor-stator interaction (RSI) phenomenon always has to be considered carefully during the design phase to avoid operational issues later on. The RSI dynamic response amplitudes are driven by three main factors: (1) pressure forcing amplitudes, (2) excitation frequencies in relation to natural frequencies and (3) damping. The prediction of the two first factors has been largely documented in the literature. However, the prediction of fluid damping has received less attention in spite of being critical when the runner is close to resonance. Experimental damping measurements in flowing water on hydrofoils were presented previously. Those results showed that the hydro-dynamic damping increased linearly with the flow. This paper presents development and validation of a mathematical model, based on momentum exchange, to predict damping due to fluid structure interaction in flowing water. The model is implemented as an analytical procedure for simple structures, such as cantilever beams, but is also implemented in more general ways using three different approaches for more complex structures such as runner blades: a finite element procedure, a CFD modal work based approach and a CFD 1DOF approach. The mathematical model and all three implementation approaches are shown to agree well with experimental results.

Replication Protein A Presents Canonical Functions and Is Also Involved in the Differentiation Capacity of Trypanosoma cruzi.

PubMed

Pavani, Raphael Souza; da Silva, Marcelo Santos; Fernandes, Carlos Alexandre Henrique; Morini, Flavia Souza; Araujo, Christiane Bezerra; Fontes, Marcos Roberto de Mattos; Sant'Anna, Osvaldo Augusto; Machado, Carlos Renato; Cano, Maria Isabel; Fragoso, Stenio Perdigão; Elias, Maria Carolina

2016-12-01

Replication Protein A (RPA), the major single stranded DNA binding protein in eukaryotes, is composed of three subunits and is a fundamental player in DNA metabolism, participating in replication, transcription, repair, and the DNA damage response. In human pathogenic trypanosomatids, only limited studies have been performed on RPA-1 from Leishmania. Here, we performed in silico, in vitro and in vivo analysis of Trypanosoma cruzi RPA-1 and RPA-2 subunits. Although computational analysis suggests similarities in DNA binding and Ob-fold structures of RPA from T. cruzi compared with mammalian and fungi RPA, the predicted tridimensional structures of T. cruzi RPA-1 and RPA-2 indicated that these molecules present a more flexible tertiary structure, suggesting that T. cruzi RPA could be involved in additional responses. Here, we demonstrate experimentally that the T. cruzi RPA complex interacts with DNA via RPA-1 and is directly related to canonical functions, such as DNA replication and DNA damage response. Accordingly, a reduction of TcRPA-2 expression by generating heterozygous knockout cells impaired cell growth, slowing down S-phase progression. Moreover, heterozygous knockout cells presented a better efficiency in differentiation from epimastigote to metacyclic trypomastigote forms and metacyclic trypomastigote infection. Taken together, these findings indicate the involvement of TcRPA in the metacyclogenesis process and suggest that a delay in cell cycle progression could be linked with differentiation in T. cruzi.

Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation

PubMed Central

Le Dily, François; Baù, Davide; Pohl, Andy; Vicent, Guillermo P.; Serra, François; Soronellas, Daniel; Castellano, Giancarlo; Wright, Roni H.G.; Ballare, Cecilia; Filion, Guillaume; Marti-Renom, Marc A.

2014-01-01

The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known. Here we describe the distribution of progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing), Hi-C (chromosome capture followed by high-throughput sequencing), and three-dimensional (3D) modeling techniques, we found that the borders of the ∼2000 TADs in these cells are largely maintained after hormone treatment and that up to 20% of the TADs could be considered as discrete regulatory units where the majority of the genes are either transcriptionally activated or repressed in a coordinated fashion. The epigenetic signatures of the TADs are homogeneously modified by hormones in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodeling are accompanied by differential structural changes for activated and repressed TADs, as reflected by specific and opposite changes in the strength of intra-TAD interactions within responsive TADs. Indeed, 3D modeling of the Hi-C data suggested that the structure of TADs was modified upon treatment. The differential responses of TADs to progestins and estrogens suggest that TADs could function as “regulons” to enable spatially proximal genes to be coordinately transcribed in response to hormones. PMID:25274727

Beyond Faith-Based Organizations: Using Comparative Institutional Ethnography to Understand Religious Responses to HIV and AIDS in Brazil

PubMed Central

Murray, Laura; Wittlin, Natalie; Garcia, Jonathan; Terto Jr, Veriano; Parker, Richard G.

2011-01-01

Religious institutions, which contribute to understanding of and mobilization in response to illness, play a major role in structuring social, political, and cultural responses to HIV and AIDS. We used institutional ethnography to explore how religious traditions—Catholic, Evangelical, and Afro-Brazilian—in Brazil have influenced HIV prevention, treatment, and care at the local and national levels over time. We present a typology of Brazil's division of labor and uncover overlapping foci grounded in religious ideology and tradition: care of people living with HIV among Catholics and Afro-Brazilians, abstinence education among Catholics and Evangelicals, prevention within marginalized communities among Evangelicals and Afro-Brazilians, and access to treatment among all traditions. We conclude that institutional ethnography, which allows for multilevel and interlevel analysis, is a useful methodology. PMID:21493944

pH-Responsive Mesoporous Silica and Carbon Nanoparticles for Drug Delivery

PubMed Central

Gisbert-Garzarán, Miguel; Manzano, Miguel; Vallet-Regí, María

2017-01-01

The application of nanotechnology to medicine constitutes a major field of research nowadays. In particular, the use of mesoporous silica and carbon nanoparticles has attracted the attention of numerous researchers due to their unique properties, especially when applied to cancer treatment. Many strategies based on stimuli-responsive nanocarriers have been developed to control the drug release and avoid premature release. Here, we focus on the use of the subtle changes of pH between healthy and diseased areas along the body to trigger the release of the cargo. In this review, different approximations of pH-responsive systems are considered: those based on the use of the host-guest interactions between the nanocarriers and the drugs, those based on the hydrolysis of acid-labile bonds and those based on supramolecular structures acting as pore capping agents. PMID:28952481

Beyond faith-based organizations: using comparative institutional ethnography to understand religious responses to HIV and AIDS in Brazil.

PubMed

Muñoz-Laboy, Miguel A; Murray, Laura; Wittlin, Natalie; Garcia, Jonathan; Terto, Veriano; Parker, Richard G

2011-06-01

Religious institutions, which contribute to understanding of and mobilization in response to illness, play a major role in structuring social, political, and cultural responses to HIV and AIDS. We used institutional ethnography to explore how religious traditions--Catholic, Evangelical, and Afro-Brazilian--in Brazil have influenced HIV prevention, treatment, and care at the local and national levels over time. We present a typology of Brazil's division of labor and uncover overlapping foci grounded in religious ideology and tradition: care of people living with HIV among Catholics and Afro-Brazilians, abstinence education among Catholics and Evangelicals, prevention within marginalized communities among Evangelicals and Afro-Brazilians, and access to treatment among all traditions. We conclude that institutional ethnography, which allows for multilevel and interlevel analysis, is a useful methodology.

Magnitude and nature of carbohydrate-aromatic interactions in fucose-phenol and fucose-indole complexes: CCSD(T) level interaction energy calculations.

PubMed

Tsuzuki, Seiji; Uchimaru, Tadafumi; Mikami, Masuhiro

2011-10-20

The CH/π contact structures of the fucose-phenol and fucose-indole complexes and the stabilization energies by formation of the complexes (E(form)) were studied by ab initio molecular orbital calculations. The three types of interactions (CH/π and OH/π interactions and OH/O hydrogen bonds) were compared and evaluated in a single molecular system and at the same level of theory. The E(form) calculated for the most stable CH/π contact structure of the fucose-phenol complex at the CCSD(T) level (-4.9 kcal/mol) is close to that for the most stable CH/π contact structure of the fucose-benzene complex (-4.5 kcal/mol). On the other hand the most stable CH/π contact structure of the fucose-indole complex has substantially larger E(form) (-6.5 kcal/mol). The dispersion interaction is the major source of the attraction in the CH/π contact structures of the fucose-phenol and fucose-indole complexes as in the case of the fucose-benzene complex. The electrostatic interactions in the CH/π contact structures are small (less than 1.5 kcal/mol). The nature of the interactions between the nonpolar surface of the carbohydrate and aromatic rings is completely different from that of the conventional hydrogen bonds where the electrostatic interaction is the major source of the attraction. The distributed multipole analysis and DFT-SATP analysis show that the dispersion interactions in the CH/π contact structure of fucose-indole complex are substantially larger than those in the CH/π contact structures of fucose-benzene and fucose-phenol complexes. The large dispersion interactions are responsible for the large E(form) for the fucose-indole complex.

Structural and biochemical changes in dermis of sea cucumber (Stichopus japonicus) during autolysis in response to cutting the body wall.

PubMed

Liu, Yu-Xin; Zhou, Da-Yong; Liu, Zi-Qiang; Lu, Ting; Song, Liang; Li, Dong-Mei; Dong, Xiu-Ping; Qi, Hang; Zhu, Bei-Wei; Shahidi, Fereidoon

2018-02-01

The autolysis of sea cucumber body wall is caused by endogenous proteolysis of its structural elements. However, changes in collagen fibrils, collagen fibres and microfibrils, the major structural elements in sea cucumber body wall during autolysis are less clear. Autolysis of sea cucumber (S. japonicus) was induced by cutting the body wall, and the structural and biochemical changes in its dermis were investigated using electron microscopy, differential scanning calorimetry, infrared spectroscopy, electrophoresis, and chemical analysis. During autolysis, both collagen fibres and microfibrils gradually degraded. In contrast, damage to microfibrils was more pronounced. Upon massive autolysis, collagen fibres disaggregated into collagen fibril bundles and individual fibrils due to the fracture of interfibrillar bridges. Meanwhile, excessive unfolding of collagen fibrils occurred. However, there was only slight damage to collagen monomers. Therefore, structural damage in collagen fibres, collagen fibrils and microfibrils rather than monomeric collagen accounts for autolysis of S. japonicus dermis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using intersectionality responsibly: Toward critical epistemology, structural analysis, and social justice activism.

PubMed

Moradi, Bonnie; Grzanka, Patrick R

2017-10-01

The increasing popularity of the concept of intersectionality in the social sciences, including in psychology, represents an opportunity to reflect on the state of stewardship of this concept, its roots, and its promise. In this context, the authors aim to promote responsible stewardship of intersectionality and to tip the momentum of intersectionality's flourishing toward fuller use and engagement of its roots and promise for understanding and challenging dynamics of power, privilege, and oppression. To this end, this article provides a set of guidelines for reflection and action. The authors organize these guidelines along 3 major formulations of intersectionality: intersectionality as a field of study, as analytic strategy or disposition, and as critical praxis for social justice. Ultimately, the authors call for expanding the use of intersectionality toward fuller engagement with its roots in Black feminist thought, its current interdisciplinary richness and potential, and its central aims to challenge and transform structures and systems of power, privilege, and oppression. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A Brief Review of West Nile Virus Biology.

PubMed

Londono-Renteria, Berlin; Colpitts, Tonya M

2016-01-01

West Nile virus (WNV) is an arbovirus with increased global incidence in the last decade. It is also a major cause of human encephalitis in the USA. WNV is an arthropod-transmitted virus that mainly affects birds but humans become infected as incidental dead-end hosts which can cause outbreaks in naïve populations. The main vectors of WNV are mosquitoes of the genus Culex, which preferentially feed on birds. As in many other arboviruses, the characteristics that allow Flaviviruses like WNV to replicate and transmit to different hosts are encrypted in their genome, which also contains information for the production of structural and nonstructural proteins needed for host cell infection. WNV and other Flaviviruses have developed different strategies to establish infection, replication, and successful transmission. Most of these strategies include the diversion of the host's immune responses away from the virus. In this review, we describe the molecular structure and protein function of WNV with emphasis on protein involvement in the modulation of antiviral immune responses.

Structural basis for glucose-6-phosphate activation of glycogen synthase

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

Baskaran, Sulochanadevi; Roach, Peter J.; DePaoli-Roach, Anna A.

2010-11-22

Regulation of the storage of glycogen, one of the major energy reserves, is of utmost metabolic importance. In eukaryotes, this regulation is accomplished through glucose-6-phosphate levels and protein phosphorylation. Glycogen synthase homologs in bacteria and archaea lack regulation, while the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and glucose-6-phosphate binding. We determined the crystal structures corresponding to the basal activity state and glucose-6-phosphate activated state of yeast glycogen synthase-2. The enzyme is assembled into an unusual tetramer by an insertion unique to the eukaryotic enzymes, and this subunit interface is rearranged by themore » binding of glucose-6-phosphate, which frees the active site cleft and facilitates catalysis. Using both mutagenesis and intein-mediated phospho-peptide ligation experiments, we demonstrate that the enzyme's response to glucose-6-phosphate is controlled by Arg583 and Arg587, while four additional arginine residues present within the same regulatory helix regulate the response to phosphorylation.« less

Approaches to the induction of HIV broadly neutralizing antibodies.

PubMed

Moore, Penny L; Williamson, Carolyn

2016-11-01

A vaccine that elicits antibody responses that can neutralize the diversity of HIV clades has not yet been achieved, and is a major focus of HIV vaccine research. Here, we provide an update on the barriers to eliciting such antibodies, and how advances in immunogen design may circumvent these roadblocks, focusing on data published in the last year. Studies of how broadly neutralizing antibodies (bNAbs) develop in HIV-infected donors continue to produce key insights, suggesting that for some viral targets there are common pathways to developing breadth. Germline-targeting strategies, that aim to recruit rare precursors of bNAbs, have shown promise in immunogenicity studies, and structural biology has led to advances in immunogen design. Mapping of strain-specific tier 2 vaccine responses has highlighted the challenges that remain in driving antibodies toward breadth. Elucidation of the HIV envelope structure, together with an understanding of how bNAbs emerge in vivo has guided the design of new immunogens and vaccine strategies that show promise for eliciting protective antibodies.

Recent advances in metamaterial split-ring-resonator circuits as biosensors and therapeutic agents.

PubMed

RoyChoudhury, Sohini; Rawat, Vaishali; Jalal, Ahmed Hasnain; Kale, S N; Bhansali, Shekhar

2016-12-15

Potential applications of thin film metamaterials are diverse and their realization to offer miniaturized waveguides, antennas and shielding patterns are on anvil. These artificially engineered structures can produce astonishing electromagnetic responses because of their constituents being engineered at much smaller dimensions than the wavelength of the incident electromagnetic wave, hence behaving as artificial materials. Such micro-nano dimensions of thin film metamaterial structures can be customized for various applications due to their exclusive responses to not only electromagnetic, but also to acoustic and thermal waves that surpass the natural materials' properties. In this paper, the recent major advancements in the emerging fields of diagnostics (sensors) and therapeutics involving thin film metamaterials have been reviewed and underlined; discussing their edge over conventional counterpart techniques; concentrating on their design considerations and feasible ways of achieving them. Challenges faced in sensitivity, precision, accuracy and factors that interfere with the degree of performance of the sensors are also dealt with, herein. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of Electronic Journals in Astronomy and Astrophysics Libraries and Information Centres in India: A Librarians' Perspective

NASA Astrophysics Data System (ADS)

Pathak, S. K.; Deshpande, N. J.; Rai, V.

2010-10-01

The objectives of this study were to find out whether librarians are satisfied with the present infrastructure for electronic journals and also to find out whether librarians are taking advantage of consortia. A structured questionnaire for librarians was divided into eight parts which were further sub-divided and designed to get information on various aspects of library infrastructure and usage of electronic journals. The goal was to find out the basic minimum infrastructure needed to provide access to electronic journals to a community of users and to facilitate communication in all major astronomy & astrophysics organizations in India. The study aims to highlight key insights from responses of librarians who are responsible for managing astronomy & astrophysics libraries in India and to identify the information needs of the users. Each community and discipline will have its own specific legacy of journal structure, reading, publishing, and researching practices, and time will show which kinds of e-journals are most effective and useful.

Relationships between nonlinear normal modes and response to random inputs

DOE PAGES

Schoneman, Joseph D.; Allen, Matthew S.; Kuether, Robert J.

2016-07-25

The ability to model nonlinear structures subject to random excitation is of key importance in designing hypersonic aircraft and other advanced aerospace vehicles. When a structure is linear, superposition can be used to construct its response to a known spectrum in terms of its linear modes. Superposition does not hold for a nonlinear system, but several works have shown that a system's dynamics can still be understood qualitatively in terms of its nonlinear normal modes (NNMs). Here, this work investigates the connection between a structure's undamped nonlinear normal modes and the spectrum of its response to high amplitude random forcing.more » Two examples are investigated: a spring-mass system and a clamped-clamped beam modeled within a geometrically nonlinear finite element package. In both cases, an intimate connection is observed between the smeared peaks in the response spectrum and the frequency-energy dependence of the nonlinear normal modes. In order to understand the role of coupling between the underlying linear modes, reduced order models with and without modal coupling terms are used to separate the effect of each NNM's backbone from the nonlinear couplings that give rise to internal resonances. In the cases shown here, uncoupled, single-degree-of-freedom nonlinear models are found to predict major features in the response with reasonable accuracy; a highly inexpensive approximation such as this could be useful in design and optimization studies. More importantly, the results show that a reduced order model can be expected to give accurate results only if it is also capable of accurately predicting the frequency-energy dependence of the nonlinear modes that are excited.« less

Analysis of the international and US response to the Haiti earthquake: recommendations for change.

PubMed

Kirsch, Thomas; Sauer, Lauren; Guha Sapir, Debarati

2012-10-01

The 2010 earthquake in Haiti was unprecedented in its impact. The dual loss of the Haitian government and United Nations (UN) leadership led to an atypical disaster response driven by the US government and military. Although the response was massive, the leadership and logistical support were initially insufficient, and the UN cluster system struggled with the overwhelming influx of nontraditional agencies and individuals, which complicated the health care response. Moreover, the provision of care was beyond the country's health care standards. The management of the US government resembled a whole-of-government domestic response, combined with a massive military presence that went beyond logistical support. Among the most important lessons learned were the management of the response and how it could be strengthened by adapting a structure such as the domestic National Response Framework. Also, mechanisms were needed to increase the limited personnel to surge in a major response. One obvious pool has been the military, but the military needs to increase integration with the humanitarian community and improve its own humanitarian response expertise. In addition, information management needs standardized tools and analysis to improve its use of independent agencies.

Developmental plasticity and stability in the tracheal networks supplying Drosophila flight muscle in response to rearing oxygen level.

PubMed

Harrison, Jon F; Waters, James S; Biddulph, Taylor A; Kovacevic, Aleksandra; Klok, C Jaco; Socha, John J

2018-04-01

While it is clear that the insect tracheal system can respond in a compensatory manner to both hypoxia and hyperoxia, there is substantial variation in how different parts of the system respond. However, the response of tracheal structures, from the tracheoles to the largest tracheal trunks, have not been studied within one species. In this study, we examined the effect of larval/pupal rearing in hypoxia, normoxia, and hyperoxia (10, 21 or 40kPa oxygen) on body size and the tracheal supply to the flight muscles of Drosophila melanogaster, using synchrotron radiation micro-computed tomography (SR-µCT) to assess flight muscle volumes and the major tracheal trunks, and confocal microscopy to assess the tracheoles. Hypoxic rearing decreased thorax length whereas hyperoxic-rearing decreased flight muscle volumes, suggestive of negative effects of both extremes. Tomography at the broad organismal scale revealed no evidence for enlargement of the major tracheae in response to lower rearing oxygen levels, although tracheal size scaled with muscle volume. However, using confocal imaging, we found a strong inverse relationship between tracheole density within the flight muscles and rearing oxygen level, and shorter tracheolar branch lengths in hypoxic-reared animals. Although prior studies of larger tracheae in other insects indicate that axial diffusing capacity should be constant with sequential generations of branching, this pattern was not found in the fine tracheolar networks, perhaps due to the increasing importance of radial diffusion in this regime. Overall, D. melanogaster responded to rearing oxygen level with compensatory morphological changes in the small tracheae and tracheoles, but retained stability in most of the other structural components of the tracheal supply to the flight muscles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alternate Reading Frame Protein (F Protein) of Hepatitis C Virus: Paradoxical Effects of Activation and Apoptosis on Human Dendritic Cells Lead to Stimulation of T Cells

PubMed Central

Samrat, Subodh Kumar; Li, Wen; Singh, Shakti; Kumar, Rakesh; Agrawal, Babita

2014-01-01

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected individuals due to lack, failure, or inefficiency of generated adaptive immune responses. In a minority of patients, acute infection is followed by viral clearance. The immune correlates of viral clearance are not clear yet but have been extensively investigated, suggesting that multispecific and multifunctional cellular immunity is involved. The generation of cellular immunity is highly dependent upon how antigen presenting cells (APCs) process and present various viral antigens. Various structural and non-structural HCV proteins derived from the open reading frame (ORF) have been implicated in modulation of dendritic cells (DCs) and APCs. Besides the major ORF proteins, the HCV core region also encodes an alternate reading frame protein (ARFP or F), whose function in viral pathogenesis is not clear. In the current studies, we sought to determine the role of HCV-derived ARFP in modulating dendritic cells and stimulation of T cell responses. Recombinant adenovirus vectors containing F or core protein derived from HCV (genotype 1a) were prepared and used to endogenously express these proteins in dendritic cells. We made an intriguing observation that endogenous expression of F protein in human DCs leads to contrasting effects on activation and apoptosis of DCs, allowing activated DCs to efficiently internalize apoptotic DCs. These in turn result in efficient ability of DCs to process and present antigen and to prime and stimulate F protein derived peptide-specific T cells from HCV-naive individuals. Taken together, our findings suggest important aspects of F protein in modulating DC function and stimulating T cell responses in humans. PMID:24475147

Predicting the Naturalistic Course of Major Depressive Disorder Using Clinical and Multimodal Neuroimaging Information: A Multivariate Pattern Recognition Study.

PubMed

Schmaal, Lianne; Marquand, Andre F; Rhebergen, Didi; van Tol, Marie-José; Ruhé, Henricus G; van der Wee, Nic J A; Veltman, Dick J; Penninx, Brenda W J H

2015-08-15

A chronic course of major depressive disorder (MDD) is associated with profound alterations in brain volumes and emotional and cognitive processing. However, no neurobiological markers have been identified that prospectively predict MDD course trajectories. This study evaluated the prognostic value of different neuroimaging modalities, clinical characteristics, and their combination to classify MDD course trajectories. One hundred eighteen MDD patients underwent structural and functional magnetic resonance imaging (MRI) (emotional facial expressions and executive functioning) and were clinically followed-up at 2 years. Three MDD trajectories (chronic n = 23, gradual improving n = 36, and fast remission n = 59) were identified based on Life Chart Interview measuring the presence of symptoms each month. Gaussian process classifiers were employed to evaluate prognostic value of neuroimaging data and clinical characteristics (including baseline severity, duration, and comorbidity). Chronic patients could be discriminated from patients with more favorable trajectories from neural responses to various emotional faces (up to 73% accuracy) but not from structural MRI and functional MRI related to executive functioning. Chronic patients could also be discriminated from remitted patients based on clinical characteristics (accuracy 69%) but not when age differences between the groups were taken into account. Combining different task contrasts or data sources increased prediction accuracies in some but not all cases. Our findings provide evidence that the prediction of naturalistic course of depression over 2 years is improved by considering neuroimaging data especially derived from neural responses to emotional facial expressions. Neural responses to emotional salient faces more accurately predicted outcome than clinical data. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Water table and species identity outweigh carbon and nitrogen availability in a softwater plant community

NASA Astrophysics Data System (ADS)

Vanderhaeghe, Floris; Smolders, Alfons J. P.; Roelofs, Jan G. M.; Hoffmann, Maurice

2013-02-01

Performance of aquatic macrophytes is driven by many environmental factors, and a major challenge is to understand how aquatic macrophyte communities are structured in various environments. In softwater lakes in Western Europe, hydrological state (submersed/emersed), carbon dioxide and ammonium levels and species interactions are considered as driving forces in structuring amphibious plant communities. In this study we aimed at evaluating the relative importance of these factors for four species in a competitive neighbourhood. Softwater lake habitat was simulated during one growing season in laboratory conditions, mimicking water level fluctuation, photoperiod and temperature. Artificial communities consisted of small populations of four softwater macrophyte species: Luronium natans, Baldellia ranunculoides ssp. repens, Eleocharis multicaulis and Hydrocotyle vulgaris. These communities were subjected to two levels of carbon dioxide and ammonium. Additionally, monocultures of Baldellia and Eleocharis were grown at a higher nutrient level combination in order to measure their competitive response in a community. Time (hydrological state) and species identity turned out to be the only consistently significant factors determining community composition. Plant performance was clearly species-dependent, while carbon dioxide and ammonium did not have major effects. The competitive response was significant in both Eleocharis and Baldellia. Competition intensity was highest in the emersed state. Carbon dioxide had a supplementary effect on the within-species performance in Luronium, Baldellia and Eleocharis, with high carbon dioxide level mainly resulting in more flowers and more stolons. Community outcomes and competitive responses in aquatic macrophytes appear difficult to predict, because of mixed life strategies and morphological and functional plasticity. We conclude that hydrological state was the only important environmental factor. The identity of the species that were present—implying species interactions—largely determined community outcome.

Organizational Perspectives on Rapid Response Team Structure, Function, and Cost: A Qualitative Study.

PubMed

Smith, Patricia L; McSweeney, Jean

Understanding how an organization determines structure and function of a rapid response team (RRT), as well as cost evaluation and implications, can provide foundational knowledge to guide decisions about RRTs. The objectives were to (1) identify influencing factors in organizational development of RRT structure and function and (2) describe evaluation of RRT costs. Using a qualitative, ethnographic design, nurse executives and experts in 15 moderate-size hospitals were interviewed to explore their decision-making processes in determining RRT structure and function. Face-to-face interviews were audio recorded and transcribed verbatim and verified for accurateness. Using content analysis and constant comparison, interview data were analyzed. Demographic data were analyzed using descriptive statistics. The sample included 27 participants from 15 hospitals in 5 south-central states. They described a variety of RRT responders and functions, with the majority of hospitals having a critical care charge nurse attending all RRT calls for assistance. Others described a designated RRT nurse with primary RRT duties as responder to all RRT calls. Themes of RRT development from the data included influencers, decision processes, and thoughts about cost. It is important to understand how hospitals determine optimal structure and function to enhance support of quality nursing care. Determining the impact of an RRT on costs and benefits is vital in balancing patient safety and limited resources. Future research should focus on clarifying differences between team structure and function in outcomes as well as the most effective means to estimate costs and benefits.

Stand Structure and Substrate Diversity as Two Major Drivers for Bryophyte Distribution in a Temperate Montane Ecosystem

PubMed Central

Chen, Yun; Niu, Shuai; Li, Peikun; Jia, Hongru; Wang, Hailiang; Ye, Yongzhong; Yuan, Zhiliang

2017-01-01

Elucidating the major drivers of bryophyte distribution is the first step to protecting bryophyte diversity. Topography, forest, substrates (ground, tree trunks, roots, rocks, and rotten wood), and spatial factor, which factors are the major drivers of bryophyte distribution? In this study, 53 plots were set in 400 m2 along the elevation gradient in Xiaoqinling, China. All bryophytes in the plots were collected and identified. Regression analysis was used to examine the relationship between bryophyte and substrate diversity. We compared the patterns of overall bryophyte diversity and diversity of bryophytes found on the ground, tree, and rock along elevational gradients. Canonical correspondence analysis was applied to relate species composition to selected environmental variables. The importance of topography, forest, substrates, and spatial factors was determined by variance partitioning. A total of 1378 bryophyte specimens were collected, and 240 species were identified. Bryophyte diversity was closely related to substrate diversity. The overall bryophyte diversity significantly increased with elevation; however, the response varied among ground, tree, and rock bryophytes. Tree diversity and herb layer were considered important environmental factors in determining bryophyte distribution. Species abundance was best explained by stand structure (17%), and species diversity was best explained by stand structure (35%) and substrate (40%). Results directly indicated that substrate diversity can improve bryophyte species diversity. The effects of micro-habitat formed by stand structure and substrate diversity were higher than those of spatial processes and topography factors on bryophyte distribution. This study proved that the determinant factors influencing bryophyte diversity reflect the trends in recent forest management, providing a real opportunity to improve forest biodiversity conservation. PMID:28603535

Stand Structure and Substrate Diversity as Two Major Drivers for Bryophyte Distribution in a Temperate Montane Ecosystem.

PubMed

Chen, Yun; Niu, Shuai; Li, Peikun; Jia, Hongru; Wang, Hailiang; Ye, Yongzhong; Yuan, Zhiliang

2017-01-01

Elucidating the major drivers of bryophyte distribution is the first step to protecting bryophyte diversity. Topography, forest, substrates (ground, tree trunks, roots, rocks, and rotten wood), and spatial factor, which factors are the major drivers of bryophyte distribution? In this study, 53 plots were set in 400 m 2 along the elevation gradient in Xiaoqinling, China. All bryophytes in the plots were collected and identified. Regression analysis was used to examine the relationship between bryophyte and substrate diversity. We compared the patterns of overall bryophyte diversity and diversity of bryophytes found on the ground, tree, and rock along elevational gradients. Canonical correspondence analysis was applied to relate species composition to selected environmental variables. The importance of topography, forest, substrates, and spatial factors was determined by variance partitioning. A total of 1378 bryophyte specimens were collected, and 240 species were identified. Bryophyte diversity was closely related to substrate diversity. The overall bryophyte diversity significantly increased with elevation; however, the response varied among ground, tree, and rock bryophytes. Tree diversity and herb layer were considered important environmental factors in determining bryophyte distribution. Species abundance was best explained by stand structure (17%), and species diversity was best explained by stand structure (35%) and substrate (40%). Results directly indicated that substrate diversity can improve bryophyte species diversity. The effects of micro-habitat formed by stand structure and substrate diversity were higher than those of spatial processes and topography factors on bryophyte distribution. This study proved that the determinant factors influencing bryophyte diversity reflect the trends in recent forest management, providing a real opportunity to improve forest biodiversity conservation.

Analysis/test correlation using VAWT-SDS on a step-relaxation test for the rotating Sandia 34 m test bed

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

Argueello, J.G.; Dohrmann, C.R.; Carne, T.G.

The combined analysis/test effort described in this paper compares predictions with measured data from a step-relaxation test in the absence of significant wind-driven aerodynamic loading. The process described here is intended to illustrate a method for validation of time domain codes for structural analysis of wind turbine structures. Preliminary analyses were performed to investigate the transient dynamic response that the rotating Sandia 34 m Vertical Axis Wind Turbine (VAWT) would undergo when one of the two blades was excited by step-relaxation. The calculations served two purposes. The first was for pretest planning to evaluate the relative importance of the variousmore » forces that would be acting on the structure during the test and to determine if the applied force in the step-relaxation would be sufficient to produce an excitation that was distinguishable from that produced by the aerodynamic loads. The second was to provide predictions that could subsequently be compared to the data from the test. The test was carried out specifically to help in the validation of the time-domain structural dynamics code, VAWT-SDS, which predicts the dynamic response of VAWTs subject to transient events. Post-test comparisons with the data were performed and showed a qualitative agreement between pretest predictions and measured response. However, they also showed that there was significantly more damping in the measurements than included in the predictions. Efforts to resolve this difference, including post-test analyses, were undertaken and are reported herein. The overall effort described in this paper represents a major step in the process of arriving at a validated structural dynamics code.« less

Study of the structure of turbulent shear flows at supersonic speeds and high Reynolds number

NASA Technical Reports Server (NTRS)

Smits, A. J.; Bogdonoff, S. M.

1984-01-01

A major effort to improve the accuracies of turbulence measurement techniques is described including the development and testing of constant temperature hot-wire anemometers which automatically compensate for frequency responses. Calibration and data acquisition techniques for normal and inclined wires operated in the constant temperature mode, flow geometries, and physical models to explain the observed behavior of flows are discussed, as well as cooperation with computational groups in the calculation of compression corner flows.

A Study to Develop an Improved Organizational Structure for the Provision of Administrative Support for the Delivery of Health Care at Fitzsimons Army Medical Center

DTIC Science & Technology

1978-05-01

responsibility over their activities. The branch is comprised of an officer and a civilian clerk- steno - grapher. Major activities supervised include the...obtained during interviews with the following department chiefs: Colonel (Dr.) Nicholas C. Bethlenfalvay, MC, Department of Primary Care and Com- munity...January 1978. 121nterview with Colonel (Dr.) Nicholas C. Bethlenfalvay, MC, Chief, Department of Primary Care and Community Medicine, Fitzsimons Army

Embryonic Stem Cell-Derived Neurons are a Novel, Highly Sensitive Tissue Culture Platform for Botulinum Research

DTIC Science & Technology

2011-01-01

and acceleration of toxin degradation may be more amenable to therapeutic intervention, the neuronal response to intoxication and the molecular ...References [1] L.L. Simpson, Identification of the major steps in botulinum toxin action, Annu. Rev. Pharmacol. Toxicol. 44 (2004) 167–193. [2] J.C...BoNT) therapeutics: time to think outside the BoNT?, Botulinum J 1 (2009) 261–269. [6] L.L. Simpson, The origin, structure , and pharmacological

A possible structural model of members of the CPF family of cuticular proteins implicating binding to components other than chitin

PubMed Central

Papandreou, Nikos C.; Iconomidou, Vassiliki A.; Willis, Judith H.; Hamodrakas, Stavros J.

2010-01-01

The physical properties of cuticle are determined by the structure of its two major components, cuticular proteins (CPs) and chitin, and, also, by their interactions. A common consensus region (extended R&R Consensus) found in the majority of cuticular proteins, the CPRs, binds to chitin. Previous work established that β-pleated sheet predominates in the Consensus region and we proposed that it is responsible for the formation of helicoidal cuticle. Remote sequence similarity between CPRs and a lipocalin, bovine plasma retinol binding protein (RBP), led us to suggest an antiparallel β-sheet half-barrel structure as the basic folding motif of the R&R Consensus. There are several other families of cuticular proteins. One of the best defined is CPF. Its four members in Anopheles gambiae are expressed during the early stages of either pharate pupal or pharate adult development, suggesting that the proteins contribute to the outer regions of the cuticle, the epi- and/or exocuticle. These proteins did not bind to chitin in the same assay used successfully for CPRs. Although CPFs are distinct in sequence from CPRs, the same lipocalin could also be used to derive homology models for one Anopheles gambiae and one Drosophila melanogaster CPF. For the CPFs, the basic folding motif predicted is an eight-stranded, antiparallel β-sheet, full-barrel structure. Possible implications of this structure are discussed and docking experiments were carried out with one possible Drosophila ligand, 7(Z), 11(Z)-heptacosadiene. PMID:20417215

Comparative morphology of changeable skin papillae in octopus and cuttlefish.

PubMed

Allen, Justine J; Bell, George R R; Kuzirian, Alan M; Velankar, Sachin S; Hanlon, Roger T

2014-04-01

A major component of cephalopod adaptive camouflage behavior has rarely been studied: their ability to change the three-dimensionality of their skin by morphing their malleable dermal papillae. Recent work has established that simple, conical papillae in cuttlefish (Sepia officinalis) function as muscular hydrostats; that is, the muscles that extend a papilla also provide its structural support. We used brightfield and scanning electron microscopy to investigate and compare the functional morphology of nine types of papillae of different shapes, sizes and complexity in six species: S. officinalis small dorsal papillae, Octopus vulgaris small dorsal and ventral eye papillae, Macrotritopus defilippi dorsal eye papillae, Abdopus aculeatus major mantle papillae, O. bimaculoides arm, minor mantle, and dorsal eye papillae, and S. apama face ridge papillae. Most papillae have two sets of muscles responsible for extension: circular dermal erector muscles arranged in a concentric pattern to lift the papilla away from the body surface and horizontal dermal erector muscles to pull the papilla's perimeter toward its core and determine shape. A third set of muscles, retractors, appears to be responsible for pulling a papilla's apex down toward the body surface while stretching out its base. Connective tissue infiltrated with mucopolysaccharides assists with structural support. S. apama face ridge papillae are different: the contraction of erector muscles perpendicular to the ridge causes overlying tissues to buckle. In this case, mucopolysaccharide-rich connective tissue provides structural support. These six species possess changeable papillae that are diverse in size and shape, yet with one exception they share somewhat similar functional morphologies. Future research on papilla morphology, biomechanics and neural control in the many unexamined species of octopus and cuttlefish may uncover new principles of actuation in soft, flexible tissue.

Characterization of the Antigenic Heterogeneity of Lipoarabinomannan, the Major Surface Glycolipid of Mycobacterium tuberculosis, and Complexity of Antibody Specificities toward This Antigen

PubMed Central

Choudhary, Alok; Honnen, William; Lai, Zhong; Gennaro, Maria Laura; Garcia-Viveros, Moncerrato; Sahloul, Kamar; Spencer, John S.; Chatterjee, Delphi

2018-01-01

Lipoarabinomannan (LAM), the major antigenic glycolipid of Mycobacterium tuberculosis, is an important immunodiagnostic target for detecting tuberculosis (TB) infection in HIV-1–coinfected patients, and is believed to mediate a number of functions that promote infection and disease development. To probe the human humoral response against LAM during TB infection, several novel LAM-specific human mAbs were molecularly cloned from memory B cells isolated from infected patients and grown in vitro. The fine epitope specificities of these Abs, along with those of a panel of previously described murine and phage-derived LAM-specific mAbs, were mapped using binding assays against LAM Ags from several mycobacterial species and a panel of synthetic glycans and glycoconjugates that represented diverse carbohydrate structures present in LAM. Multiple reactivity patterns were seen that differed in their specificity for LAM from different species, as well as in their dependence on arabinofuranoside branching and nature of capping at the nonreducing termini. Competition studies with mAbs and soluble glycans further defined these epitope specificities and guided the design of highly sensitive immunodetection assays capable of detecting LAM in urine of TB patients, even in the absence of HIV-1 coinfection. These results highlighted the complexity of the antigenic structure of LAM and the diversity of the natural Ab response against this target. The information and novel reagents described in this study will allow further optimization of diagnostic assays for LAM and may facilitate the development of potential immunotherapeutic approaches to inhibit the functional activities of specific structural motifs in LAM. PMID:29610143

Community perceptions of the social determinants of child health in Western Cape, South Africa: neglect as a major indicator of child health and wellness.

PubMed

Kadir, Ayesha; Marais, Frederick; Desmond, Nicola

2013-11-01

Worldwide, neglect is the most common form of child maltreatment. Data on neglect are scarce in low- and middle-income countries, and almost no qualitative research includes the voices of children. The main objective was to understand community perceptions of the social determinants of child health. The study was also intended to test the feasibility of health professionals undertaking qualitative studies of the social determinants of child health which can be used to inform clinical care and policy. The target population was people living in deprived circumstances in rural South Africa. Data collected included focus group discussions with children and adults, children's drawings, semi-structured in-depth interviews, documentary review and transect drives. Purposive sampling of poorer households was done. Recurring themes were explored using a continuous repetitive process. Data were examined using framework analysis. The main finding was that neglect owing to substance abuse was a major predictor of poor child health and wellness. This sensitive topic was introduced by children, who created a platform for discussion with and among adult participants. Adults attributed neglect to a breakdown in family structure and changing norms regarding the responsibilities of parents. Community programmes were cited by children as a source of support, while some adults felt they undermined parental responsibility. Understanding social arrangements and community support structures is best achieved at community level through a participatory, qualitative approach. These methods also enable the views of children to inform the findings. Children's input will help uncover neglect and other hidden predictors of challenges to child health, and promote a rights-based approach to care and research.

Study Acoustic Emissions from Composites

NASA Technical Reports Server (NTRS)

Walker, James L.; Workman, Gary L.

1997-01-01

The nondestructive evaluation (NDE) of future propulsion systems utilizing advanced composite structures for the storage of cryogenic fuels, such as liquid hydrogen or oxygen, presents many challenges. Economic justification for these structures requires, light weight, reusable components with an infrastructure allowing periodic evaluation of structural integrity after enduring demanding stresses during operation. A major focus has been placed on the use of acoustic emission NDE to detect propagating defects, in service, necessitating an extensive study into characterizing the nature of acoustic signal propagation at very low temperatures and developing the methodology of applying AE sensors to monitor cryogenic components. This work addresses the question of sensor performance in the cryogenic environment. Problems involving sensor mounting, spectral response and durability are addressed. The results of this work provides a common point of measure from which sensor selection can be made when testing composite components at cryogenic temperatures.

Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

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

McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline

2008-07-21

Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability butmore » diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.« less

Plaque Structural Stress Estimations Improve Prediction of Future Major Adverse Cardiovascular Events After Intracoronary Imaging.

PubMed

Brown, Adam J; Teng, Zhongzhao; Calvert, Patrick A; Rajani, Nikil K; Hennessy, Orla; Nerlekar, Nitesh; Obaid, Daniel R; Costopoulos, Charis; Huang, Yuan; Hoole, Stephen P; Goddard, Martin; West, Nick E J; Gillard, Jonathan H; Bennett, Martin R

2016-06-01

Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5-30.6; P<0.001) and minimal luminal area ≤4 mm(2) (hazard ratio: 6.6; 95% confidence interval, 2.1-20.1; P=0.036), although absolute event rates for high-risk lesions remained <10%. PSS derived from virtual-histology intravascular ultrasound was subsequently estimated in nonculprit lesions responsible for MACE (n=22) versus matched control lesions (n=22). PSS showed marked heterogeneity across and between similar lesions but was significantly increased in MACE lesions at high-risk regions, including plaque burden ≥70% (13.9±11.5 versus 10.2±4.7; P<0.001) and thin-cap fibroatheroma (14.0±8.9 versus 11.6±4.5; P=0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P=0.003) and minimal luminal area ≤4 mm(2) (P=0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS (P<0.05). Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions. © 2016 American Heart Association, Inc.

Modeling the Infrared Reverberation Response of the Circumnuclear Dusty Torus in AGNs: The Effects of Cloud Orientation and Anisotropic Illumination

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

Almeyda, Triana; Robinson, Andrew; Richmond, Michael

The obscuring circumnuclear torus of dusty molecular gas is one of the major components of active galactic nuclei (AGN). The torus can be studied by analyzing the time response of its infrared (IR) dust emission to variations in the AGN continuum luminosity, a technique known as reverberation mapping. The IR response is the convolution of the AGN ultraviolet/optical light curve with a transfer function that contains information about the size, geometry, and structure of the torus. Here, we describe a new computer model that simulates the reverberation response of a clumpy torus. Given an input optical light curve, the codemore » computes the emission of a 3D ensemble of dust clouds as a function of time at selected IR wavelengths, taking into account light travel delays. We present simulated dust emission responses at 3.6, 4.5, and 30 μ m that explore the effects of various geometrical and structural properties, dust cloud orientation, and anisotropy of the illuminating radiation field. We also briefly explore the effects of cloud shadowing (clouds are shielded from the AGN continuum source). Example synthetic light curves have also been generated, using the observed optical light curve of the Seyfert 1 galaxy NGC 6418 as input. The torus response is strongly wavelength-dependent, due to the gradient in cloud surface temperature within the torus, and because the cloud emission is strongly anisotropic at shorter wavelengths. Anisotropic illumination of the torus also significantly modifies the torus response, reducing the lag between the IR and optical variations.« less

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

PubMed Central

Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

Structural Studies of Complex Carbohydrates of Plant Cell Walls

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

Darvill, Alan; Hahn, Michael G.; O'Neill, Malcolm A.

Most of the solar energy captured by land plants is converted into the polysaccharides (cellulose, hemicellulose, and pectin) that are the predominant components of the cell wall. These walls, which account for the bulk of plant biomass, have numerous roles in the growth and development of plants. Moreover, these walls have a major impact on human life as they are a renewable source of biomass, a source of diverse commercially useful polymers, a major component of wood, and a source of nutrition for humans and livestock. Thus, understanding the molecular mechanisms that lead to wall assembly and how cell wallsmore » and their component polysaccharides contribute to plant growth and development is essential to improve and extend the productivity and value of plant materials. The proposed research will develop and apply advanced analytical and immunological techniques to study specific changes in the structures and interactions of the hemicellulosic and pectic polysaccharides that occur during differentiation and in response to genetic modification and chemical treatments that affect wall biosynthesis. These new techniques will make it possible to accurately characterize minute amounts of cell wall polysaccharides so that subtle changes in structure that occur in individual cell types can be identified and correlated to the physiological or developmental state of the plant. Successful implementation of this research will reveal fundamental relationships between polysaccharide structure, cell wall architecture, and cell wall functions.« less

Self-catalyzed cyclization of the intervening sequence RNA of Tetrahymena: inhibition by methidiumpropyl.EDTA and localization of the major dye binding sites.

PubMed Central

Tanner, N K; Cech, T R

1985-01-01

The intervening sequence (IVS) excised from the rRNA precursor of Tetrahymena thermophila is converted to a covalently closed circular RNA in the absence of proteins in vitro. This self-catalyzed cyclization reaction is inhibited by the intercalating dye methidiumpropyl.EDTA (MPE; R.P. Hertzberg and P.B. Dervan (1982) J. Am. Chem. Soc. 104, 313-315). The MPE binding sites have been localized by mapping the sites of MPE.Fe(II) cleavage of the IVS RNA. There are three major binding sites within the 414 nucleotide IVS RNA. Two of these sites coincide with the A.B and 9L.2 pairings. These are structural elements that are conserved in all group I introns and are implicated as being functionally important for splicing. We propose that interaction of MPE with these sites is responsible for dye inhibition of cyclization. The reactions of MPE.Fe(II) with an RNA of known structure, tRNAPhe, and with the IVS RNA were studied as a function of temperature, ionic strength and ethidium concentration. Based on the comparison of the reaction with these two RNAs, we conclude that the dye is a very useful probe for structural regions of large RNAs, while it provides more limited structural information about the small, compact tRNA molecule. Images PMID:2415924

Review of current status of smart structures and integrated systems

NASA Astrophysics Data System (ADS)

Chopra, Inderjit

1996-05-01

A smart structure involves distributed actuators and sensors, and one or more microprocessors that analyze the responses from the sensors and use distributed-parameter control theory to command the actuators to apply localized strains to minimize system response. A smart structure has the capability to respond to a changing external environment (such as loads or shape change) as well as to a changing internal environment (such as damage or failure). It incorporates smart actuators that allow the alteration of system characteristics (such as stiffness or damping) as well as of system response (such as strain or shape) in a controlled manner. Many types of actuators and sensors are being considered, such as piezoelectric materials, shape memory alloys, electrostrictive materials, magnetostrictive materials, electro- rheological fluids and fiber optics. These can be integrated with main load-carrying structures by surface bonding or embedding without causing any significant changes in the mass or structural stiffness of the system. Numerous applications of smart structures technology to various physical systems are evolving to actively control vibration, noise, aeroelastic stability, damping, shape and stress distribution. Applications range from space systems, fixed-wing and rotary-wing aircraft, automotive, civil structures and machine tools. Much of the early development of smart structures methodology was driven by space applications such as vibration and shape control of large flexible space structures, but now wider applications are envisaged for aeronautical and other systems. Embedded or surface-bonded smart actuators on an airplane wing or helicopter blade will induce alteration of twist/camber of airfoil (shape change), that in turn will cause variation of lift distribution and may help to control static and dynamic aeroelastic problems. Applications of smart structures technology to aerospace and other systems are expanding rapidly. Major barriers are: actuator stroke, reliable data base of smart material characteristics, non-availability of robust distributed parameter control strategies, and non-existent mathematical modeling of smart systems. The objective of this paper is to review the state-of-the-art of smart actuators and sensors and integrated systems and point out the needs for future research.

Active subsurface cellular function in the Baltic Sea Basin, IODP Exp 347

NASA Astrophysics Data System (ADS)

Reese, B. K.; Zinke, L. A.; Bird, J. T.; Lloyd, K. G.; Marshall, I.; Amend, J.; Jørgensen, B. B.

2016-12-01

The Baltic Sea Basin is a unique depositional setting that has experienced periods of glaciation and deglaciation as a result of global temperature fluctuations over the course of several hundred thousand years. This has resulted in laminated sediments formed during periods with strong permanent salinity stratification. The high sedimentation rates (100-500 cm/1000 y) make this an ideal setting to understand the microbial structure of a deep biosphere community in a high-organic matter environment. The responses of deep sediment microbial communities to variations in conditions during and after deposition are poorly understood. Samples were collected through scientific drilling during the International Ocean Discovery Program (IODP) Expedition 347 on board the Greatship Manisha, September-November 2013. We examined the active microbial community structure using the 16S rRNA gene transcript and active functional genes through metatranscriptome sequencing. Major biogeochemical shifts have been observed in response to the depositional history between the limnic, brackish, and marine phases. The microbial community structure in the BSB is diverse and reflective of the unique changes in the geochemical profile. These data further define the existence life in the deep subsurface and the survival mechanisms required for this extreme environment.

Micromechanics and Piezo Enhancements of HyperSizer

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Bednarcyk, Brett A.; Yarrington, Phillip; Collier, Craig S.

2006-01-01

The commercial HyperSizer aerospace-composite-material-structure-sizing software has been enhanced by incorporating capabilities for representing coupled thermal, piezoelectric, and piezomagnetic effects on the levels of plies, laminates, and stiffened panels. This enhancement is based on a formulation similar to that of the pre-existing HyperSizer capability for representing thermal effects. As a result of this enhancement, the electric and/or magnetic response of a material or structure to a mechanical or thermal load, or its mechanical response to an applied electric or magnetic field can be predicted. In another major enhancement, a capability for representing micromechanical effects has been added by establishment of a linkage between HyperSizer and Glenn Research Center s Micromechanics Analysis Code With Generalized Method of Cells (MAC/GMC) computer program, which was described in several prior NASA Tech Briefs articles. The linkage enables Hyper- Sizer to localize to the fiber and matrix level rather than only to the ply level, making it possible to predict local failures and to predict properties of plies from those of the component fiber and matrix materials. Advanced graphical user interfaces and database structures have been developed to support the new HyperSizer micromechanics capabilities.

Synthesis and Crystal Structure Study of 2’-Se-Adenosine-Derivatized DNA

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

Sheng, J.; Salon, J; Gan, J

2010-01-01

The selenium derivatization of nucleic acids is a novel and promising strategy for 3D structure determination of nucleic acids. Selenium can serve as an excellent anomalous scattering center to solve the phase problem, which is one of the two major bottlenecks in macromolecule X-ray crystallography. The other major bottleneck is crystallization. It has been demonstrated that the incorporated selenium functionality at the 2'-positions of the nucleosides and nucleotides is stable and does not cause significant structure perturbation. Furthermore, it was observed that the 2'-Se-derivatization could facilitate crystallization of oligonucleotides with fast crystal growth and high diffraction quality. Herein, we describemore » a convenient synthesis of the 2'-Se-adenosine phosphoramidite, and report the first synthesis and X-ray crystal structure determination of the DNA containing the 2'-Se-A derivatization. The 3D structure of 2'-Se-A-DNA decamer [5'-GTACGCGT(2'-Se-A)C-3']{sub 2} was determined at 1.75 {angstrom} resolution, the 2'-Se-functionality points to the minor groove, and the Se-modified and native structures are virtually identical. Moreover, we have observed that the 2'-Se-A modification can greatly facilitate the crystal growth with high diffraction quality. In conjunction with the crystallization facilitation by the 2'-Se-U and 2'-Se-T, this novel observation on the 2'-Se-A functionality suggests that the 2'-Se moiety is sole responsible for the crystallization facilitation and the identity of nucleobases does not influence the crystal growth significantly.« less

Male Responses to Conspecific Advertisement Signals in the Field Cricket Gryllus rubens (Orthoptera: Gryllidae)

PubMed Central

Jang, Yikweon

2011-01-01

In many species males aggregate and produce long-range advertisement signals to attract conspecific females. The majority of the receivers of these signals are probably other males most of the time, and male responses to competitors' signals can structure the spatial and temporal organization of the breeding aggregation and affect male mating tactics. I quantified male responses to a conspecific advertisement stimulus repeatedly over three age classes in Gryllus rubens (Orthoptera: Gryllidae) in order to estimate the type and frequency of male responses to the broadcast stimulus and to determine the factors affecting them. Factors tested included body size, wing dimorphism, age, and intensity of the broadcast stimulus. Overall, males employed acoustic response more often than positive phonotactic response. As males aged, the frequency of positive phonotactic response decreased but that of the acoustic response increased. That is, males may use positive phonotaxis in the early stages of their adult lives, possibly to find suitable calling sites or parasitize calling males, and then later in life switch to acoustic responses in response to conspecific advertisement signals. Males with smaller body size more frequently exhibited acoustic responses. This study suggests that individual variation, more than any factors measured, is critical for age-dependent male responses to conspecific advertisement signals. PMID:21283758

Male responses to conspecific advertisement signals in the field cricket Gryllus rubens (Orthoptera: Gryllidae).

PubMed

Jang, Yikweon

2011-01-20

In many species males aggregate and produce long-range advertisement signals to attract conspecific females. The majority of the receivers of these signals are probably other males most of the time, and male responses to competitors' signals can structure the spatial and temporal organization of the breeding aggregation and affect male mating tactics. I quantified male responses to a conspecific advertisement stimulus repeatedly over three age classes in Gryllus rubens (Orthoptera: Gryllidae) in order to estimate the type and frequency of male responses to the broadcast stimulus and to determine the factors affecting them. Factors tested included body size, wing dimorphism, age, and intensity of the broadcast stimulus. Overall, males employed acoustic response more often than positive phonotactic response. As males aged, the frequency of positive phonotactic response decreased but that of the acoustic response increased. That is, males may use positive phonotaxis in the early stages of their adult lives, possibly to find suitable calling sites or parasitize calling males, and then later in life switch to acoustic responses in response to conspecific advertisement signals. Males with smaller body size more frequently exhibited acoustic responses. This study suggests that individual variation, more than any factors measured, is critical for age-dependent male responses to conspecific advertisement signals.

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth

PubMed Central

Foley, Joseph; Hill, Shannon E.; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-01-01

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the entire cascade of aggregation intermediates formed along each pathway. PMID:24089713

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth

NASA Astrophysics Data System (ADS)

Foley, Joseph; Hill, Shannon E.; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-09-01

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the entire cascade of aggregation intermediates formed along each pathway.

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth.

PubMed

Foley, Joseph; Hill, Shannon E; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-09-28

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the entire cascade of aggregation intermediates formed along each pathway.

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

He Yuxian; Li Jingjing; Jiang Shibo

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbsmore » as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not bind to soluble and cell-associated angiotensin-converting enzyme 2 (ACE2), the functional receptor for SARS-CoV and failed to block S protein-mediated pseudovirus entry, indicating that this point mutation also disrupted the receptor-binding motif (RBM) in the RBD. Taken together, these data provide direct evidence to show that a single amino acid residue at key position in the RBD can determine the major function of SARS-CoV S protein and imply for designing SARS vaccines and therapeutics.« less

Broad-area detection of structural irregularities in composites using fibre Bragg gratings

NASA Astrophysics Data System (ADS)

Davis, Claire E.; Norman, Patrick; Moss, Scott; Ratcliffe, Colin; Crane, Roger

2010-04-01

The Structural Irregularity and Damage Evaluation Routine (SIDER) is a broadband vibration-based technique that uses features in complex curvature operating shapes to locate damage and other areas with structural stiffness variations. It is designed for the inspection of large-scale composite structures not amenable to more conventional inspection methods. The current SIDER methodology relies on impact excitation at a series of grid points on the structure and records the response using a small number of accelerometers to determine the operational curvature shapes. This paper reports on a modification to the SIDER technique whereby the acceleration measurements are replaced with in-plane strain measurements using Fibre Bragg Gratings (FBGs). One of the major challenges associated with using Bragg gratings for this type of response measurement is that the strains induced by structural vibrations tend to be low, particularly at higher frequencies. This paper also reports on the development of an intensity-based, swept wavelength interrogation system to facilitate these measurements. The modified SIDER system was evaluated on an E-glass/vinyl ester composite test beam containing a machined notch. The measurements accurately detected the presence and location of the notch. The distributive capacity of FBGs means that these sensors have the potential to replace the excitation grid with a measurement grid, allowing for single point or environmental excitation. The spatially separated measurements of strain can be used to provide the curvature shapes directly. This change in approach could potentially transition SIDER from an interval-based, broad-area inspection tool to an in-service structural health monitoring system.

Ultrafast and low barrier motions in the photoreactions of the green fluorescent protein.

PubMed

van Thor, Jasper J; Georgiev, Georgi Y; Towrie, Michael; Sage, J Timothy

2005-09-30

Green fluorescent protein (GFP) fluoresces efficiently under blue excitation despite major electrostatic rearrangements resulting from photoionization of the chromophore and neutralization of Glu-222. A competing phototransformation process, which ionizes the chromophore and decarboxylates Glu-222, mimics the electrostatic and structural changes in the fluorescence photocycle. Structural and spectroscopic analysis of the cryogenically stabilized photoproduct at 100 K and a structurally annealed intermediate of the phototransformed protein at 170 K reveals distinct structural relaxations involving protein, chromophore, solvent, and photogenerated CO2. Strong structural changes of the 100 K photoproduct after decarboxylation appear exclusively within 15 angstroms of the chromophore and include the electrostatically driven perturbations of Gln-69, Cys-70, and water molecules in an H-bonding network connecting the chromophore. X-ray crystallography to 1.85 angstroms resolution and static and picosecond time-resolved IR spectroscopy identify structural mechanisms common to phototransformation and to the fluorescence photocycle. In particular, the appearance of a 1697 cm(-1) (+) difference band in both photocycle and phototransformation intermediates is a spectroscopic signature for the structural perturbation of Gln-69. This is taken as evidence for an electrostatically driven dynamic response that is common to both photoreaction pathways. The interactions between the chromophore and the perturbed residues and solvent are decreased or removed in the T203H single and T203H/Q69L double mutants, resulting in a strong reduction of the fluorescence quantum yield. This suggests that the electrostatic response to the transient formation of a buried charge in the wild type is important for the bright fluorescence.

Psychotherapy for Major Depressive Disorder and Generalized Anxiety Disorder: A Health Technology Assessment

PubMed Central

McMartin, Kristen; Gajic-Veljanoski, Olga; Wells, David; Higgins, Caroline; Walter, Melissa

2017-01-01

Background Major depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in Canada; both are associated with a high societal and economic burden. Treatment for major depressive disorder and generalized anxiety disorder consists of pharmacological and psychological interventions. Three commonly used psychological interventions are cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The objectives of this report were to assess the effectiveness and safety of these types of therapy for the treatment of adults with major depressive disorder and/or generalized anxiety disorder, to assess the cost-effectiveness of structured psychotherapy (CBT or interpersonal therapy), to calculate the budget impact of publicly funding structured psychotherapy, and to gain a greater understanding of the experiences of people with major depressive disorder and/or generalized anxiety disorder. Methods We performed a literature search on October 27, 2016, for systematic reviews that compared CBT, interpersonal therapy, or supportive therapy with usual care, waitlist control, or pharmacotherapy in adult outpatients with major depressive disorder and/or generalized anxiety disorder. We developed an individual-level state-transition probabilistic model for a cohort of adult outpatients aged 18 to 75 years with a primary diagnosis of major depressive disorder to determine the cost-effectiveness of individual or group CBT (as a representative form of structured psychotherapy) versus usual care. We also estimated the 5-year budget impact of publicly funding structured psychotherapy in Ontario. Finally, we interviewed people with major depressive disorder and/or generalized anxiety disorder to better understand the impact of their condition on their daily lives and their experience with different treatment options, including psychotherapy. Results Interpersonal therapy compared with usual care reduced posttreatment major depressive disorder scores (standardized mean difference [SMD]: 0.24, 95% confidence interval [CI]: −0.47 to −0.02) and reduced relapse/recurrence in patients with major depressive disorder (relative risk [RR]: 0.41, 95% CI: 0.27–0.63). Supportive therapy compared with usual care improved major depressive disorder scores (SMD: 0.58, 95% CI: 0.45–0.72) and increased posttreatment recovery (odds ratio [OR]: 2.71, 95% CI: 1.19–6.16) in patients with major depressive disorder. CBT compared with usual care increased response (OR: 1.58, 95% CI: 1.11–2.26) and recovery (OR: 3.42, 95% CI: 1.98–5.93) in patients with major depressive disorder and decreased relapse/recurrence (RR: 0.68, 95% CI: 0.65–0.87]). For patients with generalized anxiety disorder, CBT improved symptoms posttreatment (SMD: 0.80, 95% CI: 0.67–0.93), improved clinical response posttreatment (RR: 0.64, 95% CI: 0.55–0.74), and improved quality-of-life scores (SMD: 0.44, 95% CI: 0.06–0.82). There was a significant difference in posttreatment recovery (OR: 1.98, 95% CI: 1.11–3.54) and mean major depressive disorder symptom scores (weighted mean difference: −3.07, 95% CI: −4.69 to −1.45) for patients who received individual versus group CBT. Details about the providers of psychotherapy were rarely reported in the systematic reviews we examined. In the base case probabilistic cost–utility analysis, compared with usual care, both group and individual CBT were associated with increased survival: 0.11 quality-adjusted life-years (QALYs) (95% credible interval [CrI]: 0.03–0.22) and 0.12 QALYs (95% CrI: 0.03–0.25), respectively. Group CBT provided by nonphysicians was associated with the smallest increase in discounted costs: $401 (95% CrI: $1,177 to 1,665). Group CBT provided by physicians, individual CBT provided by nonphysicians, and individual CBT provided by physicians were associated with the incremental costs of $1,805 (95% CrI: 65–3,516), $3,168 (95% CrI: 889–5,624), and $5,311 (95% CrI: 2,539–8,938), respectively. The corresponding incremental cost-effectiveness ratio (ICER) was lowest for group CBT provided by nonphysicians ($3,715/QALY gained) and highest for individual CBT provided by physicians ($43,443/QALY gained). In the analysis that ranked best strategies, individual CBT versus group CBT provided by nonphysicians yielded an ICER of $192,618 per QALY. The probability of group CBT provided by nonphysicians being cost-effective versus usual care was greater than 95% for all willingness-to-pay thresholds over $20,000 per QALY and was around 88% for individual CBT provided by physicians at a threshold of $100,000 per QALY. We estimated that adding structured psychotherapy to usual care over the next 5 years would result in a net budget impact of $68 million to $529 million, depending on a range of factors. We also estimated that to provide structured psychotherapy to all adults with major depressive disorder (alone or combined with generalized anxiety disorder) in Ontario by 2021, an estimated 500 therapists would be needed to provide group therapy, and 2,934 therapists would be needed to provide individual therapy. People with major depressive disorder and/or generalized anxiety disorder with whom we spoke reported finding psychotherapy effective, but they also reported experiencing a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. Participants reported wanting more freedom to choose the type of psychotherapy they received. Conclusions Compared with usual care, treatment with CBT, interpersonal therapy, or supportive therapy significantly reduces depression symptoms posttreatment. CBT significantly reduces anxiety symptoms posttreatment in patients with generalized anxiety disorder. Compared with usual care, treatment with structured psychotherapy (CBT or interpersonal therapy) represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder. The most affordable option is group structured psychotherapy provided by nonphysicians, with the selective use of individual structured psychotherapy provided by nonphysicians or physicians for those who would benefit most from it (i.e., patients who are not engaging well with or adhering to group therapy). PMID:29213344

Mapping structural landmarks, ligand binding sites and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions and variation in phenotypes in inherited diseases affecting basement membranes

PubMed Central

Des Parkin, J.; San Antonio, James D.; Pedchenko, Vadim; Hudson, Billy; Jensen, Shane T.; Savige, Judy

2016-01-01

Collagen IV is the major protein found in basement membranes. It comprises 3 heterotrimers (α1α1α2, α3α4α5, and α5α5α6) that form distinct networks, and are responsible for membrane strength and integrity. We constructed linear maps of the collagen IV heterotrimers (‘interactomes’) that indicated major structural landmarks, known and predicted ligand-binding sites, and missense mutations, in order to identify functional and disease-associated domains, potential interactions between ligands, and genotype-phenotype relationships. The maps documented more than 30 known ligand-binding sites as well as motifs for integrins, heparin, von Willebrand factor (VWF), decorin and bone morphogenetic protein (BMP). They predicted functional domains for angiogenesis and haemostasis, and disease domains for autoimmunity, tumor growth and inhibition, infection and glycation. Cooperative ligand interactions were indicated by binding site proximity, for example, between integrins, matrix metalloproteinases and heparin. The maps indicated that mutations affecting major ligand-binding sites, for example for Von Hippel Lindau (VHL) protein in the α1 chain or integrins in the α5 chain, resulted in distinctive phenotypes (Hereditary Angiopathy, Nephropathy, Aneurysms and muscle Cramps (HANAC) syndrome, and early onset Alport syndrome respectively). These maps further our understanding of basement membrane biology and disease, and suggest novel membrane interactions, functions, and therapeutic targets. PMID:21280145

ROS and brain diseases: the good, the bad, and the ugly.

PubMed

Popa-Wagner, Aurel; Mitran, Smaranda; Sivanesan, Senthilkumar; Chang, Edwin; Buga, Ana-Maria

2013-01-01

The brain is a major metabolizer of oxygen and yet has relatively feeble protective antioxidant mechanisms. This paper reviews the Janus-faced properties of reactive oxygen species. It will describe the positive aspects of moderately induced ROS but it will also outline recent research findings concerning the impact of oxidative and nitrooxidative stress on neuronal structure and function in neuropsychiatric diseases, including major depression. A common denominator of all neuropsychiatric diseases including schizophrenia and ADHD is an increased inflammatory response of the brain caused either by an exposure to proinflammatory agents during development or an accumulation of degenerated neurons, oxidized proteins, glycated products, or lipid peroxidation in the adult brain. Therefore, modulation of the prooxidant-antioxidant balance provides a therapeutic option which can be used to improve neuroprotection in response to oxidative stress. We also discuss the neuroprotective role of the nuclear factor erythroid 2-related factor (Nrf2) in the aged brain in response to oxidative stressors and nanoparticle-mediated delivery of ROS-scavenging drugs. The antioxidant therapy is a novel therapeutic strategy. However, the available drugs have pleiotropic actions and are not fully characterized in the clinic. Additional clinical trials are needed to assess the risks and benefits of antioxidant therapies for neuropsychiatric disorders.

Mapping Kainate Activation of Inner Neurons in the Rat Retina

PubMed Central

Nivison-Smith, Lisa; Sun, Daniel; Fletcher, Erica L.; Marc, Robert E.; Kalloniatis, Michael

2014-01-01

Kainate receptors mediate fast, excitatory synaptic transmission for a range of inner neurons in the mammalian retina. However, allocation of functional kainate receptors to known cell types and their sensitivity remains unresolved. Using the cation channel probe 1-amino-4-guanidobutane agmatine (AGB), we investigated kainate sensitivity of neurochemically identified cell populations within the structurally intact rat retina. Most inner retinal neuron populations responded to kainate in a concentration-dependent manner. OFF cone bipolar cells demonstrated the highest sensitivity of all inner neurons to kainate. Immunocytochemical localization of AGB and macromolecular markers confirmed that type 2 bipolar cells were part of this kainate-sensitive population. The majority of amacrine (ACs) and ganglion cells (GCs) showed kainate responses with different sensitivities between major neurochemical classes (γ-aminobutyric acid [GABA]/glycine ACs > glycine ACs > GABA ACs; glutamate [Glu]/weakly GABA GCs > Glu GCs). Conventional and displaced cholinergic ACs were highly responsive to kainate, whereas dopaminergic ACs do not appear to express functional kainate receptors. These findings further contribute to our understanding of neuronal networks in complex multicellular tissues. PMID:23348566

Crystal Structure of Green Fluorescent Protein Clover and Design of Clover-Based Redox Sensors.

PubMed

Campbell, Benjamin C; Petsko, Gregory A; Liu, Ce Feng

2018-02-06

We have determined the crystal structure of Clover, one of the brightest fluorescent proteins, and found that its T203H/S65G mutations relative to wild-type GFP lock the critical E222 side chain in a fixed configuration that mimics the major conformer of that in EGFP. The resulting equilibrium shift to the predominantly deprotonated chromophore increases the extinction coefficient (EC), opposes photoactivation, and is responsible for the bathochromic shift. Clover's brightness can further be attributed to a π-π stacking interaction between H203 and the chromophore. Consistent with these observations, the Clover G65S mutant reversed the equilibrium shift, dramatically decreased the EC, and made Clover photoactivatable under conditions that activated photoactivatable GFP. Using the Clover structure, we rationally engineered a non-photoactivatable redox sensor, roClover1, and determined its structure as well as that of its parental template, roClover0.1. These high-resolution structures provide deeper insights into structure-function relationships in GFPs and may aid the development of excitation-improved ratiometric biosensors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stratigraphic and structural evolution of the Selenga Delta Accommodation Zone, Lake Baikal Rift, Siberia

USGS Publications Warehouse

Scholz, C.A.; Hutchinson, D.R.

2000-01-01

Seismic reflection profiles from the Lake Baikal Rift reveal extensive details about the sediment thickness, structural geometry and history of extensional deformation and syn-rift sedimentation in this classic continental rift. The Selenga River is the largest single source of terrigenous input into Lake Baikal, and its large delta sits astride the major accommodation zone between the Central and South basins of the lake. Incorporating one of the world's largest lacustrine deltas, this depositional system is a classic example of the influence of rift basin structural segmentation on a major continental drainage. More than 3700 km of deep basin-scale multi-channel seismic reflection (MCS) data were acquired during the 1989 Russian and the 1992 Russian–American field programs. The seismic data image most of the sedimentary section, including pre-rift basement in several localities. The MCS data reveal that the broad bathymetric saddle between these two major half-graben basins is underlain by a complex of severely deformed basement blocks, and is not simply a consequence of long-term deltaic deposition. Maximum sediment thickness is estimated to be more than 9 km in some areas around the Selenga Delta. Detailed stratigraphic analyses of the Selenga area MCS data suggest that modes of deposition have shifted markedly during the history of the delta. The present mode of gravity- and mass-flow sedimentation that dominates the northern and southern parts of the modern delta, as well as the pronounced bathymetric relief in the area, are relatively recent developments in the history of the Lake Baikal Rift. Several episodes of major delta progradation, each extending far across the modern rift, can be documented in the MCS data. The stratigraphic framework defined by these prograding deltaic sequences can be used to constrain the structural as well as depositional evolution of this part of the Baikal Rift. An age model has been established for this stratigraphy, by tying the delta sequences to the site of the Baikal Drilling Project 1993 Drill Hole. Although the drill hole is only 100 m deep, and the base of the cores is only ∼670 ka in age, ages were extrapolated to deeper stratigraphic intervals using the Reflection-Seismic-Radiocarbon method of Cohen et al. (1993). The deep prograding delta sequences now observed in the MCS data probably formed in response to major fluctuations in sediment supply, rather than in response to shifts in lake level. This stratigraphic framework and age model suggest that the deep delta packages developed at intervals of approximately 400 ka and may have formed as a consequence of climate changes affiliated with the northern hemisphere glaciations. The stratigraphic analysis also suggests that the Selenga Basin and Syncline developed as a distinct depocentre only during the past ∼2–3 Ma.

A Participatory Action Research Pilot Study of Urban Health Disparities Using Rapid Assessment Response and Evaluation

PubMed Central

Brown, David Richard; Hernández, Agueda; Saint-Jean, Gilbert; Evans, Siân; Tafari, Ida; Brewster, Luther G.; Celestin, Michel J.; Gómez-Estefan, Carlos; Regalado, Fernando; Akal, Siri; Nierenberg, Barry; Kauschinger, Elaine D.; Schwartz, Robert; Page, J. Bryan

2008-01-01

Healthy People 2010 made it a priority to eliminate health disparities. We used a rapid assessment response and evaluation (RARE) to launch a program of participatory action research focused on health disparities in an urban, disadvantaged Black community serviced by a major south Florida health center. We formed partnerships with community members, identified local health disparities, and guided interventions targeting health disparities. We describe the RARE structure used to triangulate data sources and guide intervention plans as well as findings and conclusions drawn from scientific literature and epidemiological, historic, planning, clinical, and ethnographic data. Disenfranchisement and socioeconomic deprivation emerged as the principal determinants of local health disparities and the most appropriate targets for intervention. PMID:18048802

Determination of C-glucosidic ellagitannins in Lythri salicariaeherba by ultra-high performance liquid chromatography coupled with charged aerosol detector: method development and validation.

PubMed

Granica, Sebastian; Piwowarski, Jakub P; Kiss, Anna K

2014-01-01

Lythri salicariaeherba is a pharmacopoeial plant material used by patients in the form of infusions in the treatment of acute diarrhoea. According to its pharmacopoeial monograph it is standardised for total tannin content, which should be not less than 5.0% using pyrogallol as a standard. Previous studies have shown that aqueous extracts from Lythri herba contain mainly ellagitannins among which vescalagin, castalagin and salicarinins A and B are dominating constituents. To develop and validate an efficient UHPLC coupled with a charged aerosol detector (CAD) method for quantification of four major ellagitannins in Lythri salicariaeherba and in one commercial preparation. Extraction conditions of ellagitannins from plant material were optimised. The relative response factors for vescalagin, castalagin and salicarinins A and B using gallic acid as an external standard were determined for the CAD detector. Then, a UHPLC method for quantification of ellagitannins was developed and validated. Four major ellagitannins were quantified in four samples of Lythri herba and in one commercial preparation. The sum of ellagitannins for each sample was determined, which varied from 30.66 to 48.80 mg/g of raw material and 16.57 mg per capsule for the preparation investigated. The first validated UHPLC/CAD UHPLC-CAD method for quantification of four major ellagitannins was developed. The universality of the CAD response was evaluated and it is shown that although all compounds analysed have similar structures their CAD response differs significantly. Copyright © 2013 John Wiley & Sons, Ltd.

Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: Implications for determinant spreading.

PubMed

McLaughlin, Kerry A; Richardson, Carolyn C; Williams, Stefan; Bonifacio, Ezio; Morgan, Diana; Feltbower, Richard G; Powell, Michael; Rees Smith, Bernard; Furmaniak, Jadwiga; Christie, Michael R

2015-10-01

Diversification of autoimmunity to islet autoantigens is critical for progression to Type 1 diabetes. B-cells participate in diversification by modifying antigen processing, thereby influencing which peptides are presented to T-cells. In Type 1 diabetes, JM antibodies are associated with T-cell responses to PTP domain peptides. We investigated whether this is the consequence of close structural alignment of JM and PTP domain determinants on IA-2. Fab fragments of IA-2 antibodies with epitopes mapped to the JM domain blocked IA-2 binding of antibodies that recognise epitopes in the IA-2 PTP domain. Peptides from both the JM and PTP domains were protected from degradation during proteolysis of JM antibody:IA-2 complexes and included those representing major T-cell determinants in Type 1 diabetes. The results demonstrate close structural relationships between JM and PTP domain epitopes on IA-2. Stabilisation of PTP domain peptides during proteolysis in JM-specific B-cells may explain determinant spreading in IA-2 autoimmunity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Application of ultra high pressure (UHP) in starch chemistry.

PubMed

Kim, Hyun-Seok; Kim, Byung-Yong; Baik, Moo-Yeol

2012-01-01

Ultra high pressure (UHP) processing is an attractive non-thermal technique for food treatment and preservation at room temperature, with the potential to achieve interesting functional effects. The majority of UHP process applications in food systems have focused on shelf-life extension associated with non-thermal sterilization and a reduction or increase in enzymatic activity. Only a few studies have investigated modifications of structural characteristics and/or protein functionalities. Despite the rapid expansion of UHP applications in food systems, limited information is available on the effects of UHP on the structural and physicochemical properties of starch and/or its chemical derivatives included in most processed foods as major ingredients or minor additives. Starch and its chemical derivatives are responsible for textural and physical properties of food systems, impacting their end-use quality and/or shelf-life. This article reviews UHP processes for native (unmodified) starch granules and their effects on the physicochemical properties of UHP-treated starch. Furthermore, functional roles of UHP in acid-hydrolysis, hydroxypropylation, acetylation, and cross-linking reactions of starch granules, as well as the physicochemical properties of UHP-assisted starch chemical derivatives, are discussed.

[Changes in Spatial Organization of Cortical Rhythm Vibrations in Children uner the Influence of Music].

PubMed

Shepovalnikov, A N; Egorov, M V

2015-01-01

Changes is systemic brain activity under influence of classical music (minor and major music) were studied at two groups of healthy children aged 5-6 years (n = 53). In 25 of studied children the Luscher test showed increased level of anxiety which significantly decreased after music therapy sessions. Bioelectrical cortical activity registered from 20 unipolar leads was subjected to correlation, coherence and factor analysis. Also the dynamics of the power spectrum for each of the EEG was studied. According to EEG all children after listening to both minor and major tones showed reorganization of brain rhythm structure accompanied by a decrease in the level of coherence and correlation of EEG; also was found significant and almost universal decrease in the EEG power spectrum. Registered EEG changes under the influence of classical music seems to reflect a decrease in excess of "internal tension" and weakening degree of "stiffness" to ensure the activity of cerebral structures responsible for mechanisms of "basic integration" which maintain constant readiness of brain to rapid and complete inclusion in action.

Structure, Expression, Chromosomal Location and Product of the Gene Encoding Adh2 in Petunia

PubMed Central

Gregerson, R. G.; Cameron, L.; McLean, M.; Dennis, P.; Strommer, J.

1993-01-01

In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes. PMID:8096485

32 CFR 643.5 - Responsibilities of major commands (MACOMS) and special staff agencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Responsibilities of major commands (MACOMS) and special staff agencies. 643.5 Section 643.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE General § 643.5 Responsibilities of major commands...

32 CFR 643.5 - Responsibilities of major commands (MACOMS) and special staff agencies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 4 2013-07-01 2013-07-01 false Responsibilities of major commands (MACOMS) and special staff agencies. 643.5 Section 643.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE General § 643.5 Responsibilities of major commands...

32 CFR 643.5 - Responsibilities of major commands (MACOMS) and special staff agencies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Responsibilities of major commands (MACOMS) and special staff agencies. 643.5 Section 643.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE General § 643.5 Responsibilities of major commands...

32 CFR 643.5 - Responsibilities of major commands (MACOMS) and special staff agencies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 4 2012-07-01 2011-07-01 true Responsibilities of major commands (MACOMS) and special staff agencies. 643.5 Section 643.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE General § 643.5 Responsibilities of major commands...

32 CFR 643.5 - Responsibilities of major commands (MACOMS) and special staff agencies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 4 2014-07-01 2013-07-01 true Responsibilities of major commands (MACOMS) and special staff agencies. 643.5 Section 643.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE General § 643.5 Responsibilities of major commands...

Investigating the candidacy of the serotype specific rhamnan polysaccharide based glycoconjugates to prevent disease caused by the dental pathogen Streptococcus mutans.

PubMed

St Michael, Frank; Yang, Qingling; Cairns, Chantelle; Vinogradov, Evgeny; Fleming, Perry; Hayes, Alexander C; Aubry, Annie; Cox, Andrew D

2018-02-01

Dental caries remains a major health issue and the Gram-positive bacterium Streptococcus mutans is considered as the major pathogen causing caries. More recently, S. mutans has been recognised as a cause of endocarditis, ulcerative colitis and fatty acid liver disease along with the likelihood of increased cerebral hemorrhage following a stroke if S. mutans is present systemically. We initiated this study to examine the vaccine candidacy of the serotype specific polysaccharides elaborated by S. mutans. We have confirmed the carbohydrate structures for the serotype specific rhamnan containing polysaccharides from serotypes c, f and k. We have prepared glycoconjugate vaccines using the rhamnan containing polymers from serotypes f and k and immunised mice and rabbits. We consistently obtained a robust immune response to the glycoconjugates with cross-reactivity consistent with the structural similarities of the polymers from the different serotypes. We developed an opsonophagocytic assay which illustrated the ability of the post-immune sera to facilitate opsonophagocytic killing of the homologous and heterologous serotypes at titers consistent with the structural homologies. We conclude that glycoconjugates of the rhamnan polymers of S. mutans are a potential vaccine candidate to target dental caries and other sequelae following the escape of S. mutans from the oral cavity.

Effects of seawater acidification on a coral reef meiofauna community

NASA Astrophysics Data System (ADS)

Sarmento, V. C.; Souza, T. P.; Esteves, A. M.; Santos, P. J. P.

2015-09-01

Despite the increasing risk that ocean acidification will modify benthic communities, great uncertainty remains about how this impact will affect the lower trophic levels, such as members of the meiofauna. A mesocosm experiment was conducted to investigate the effects of water acidification on a phytal meiofauna community from a coral reef. Community samples collected from the coral reef subtidal zone (Recife de Fora Municipal Marine Park, Porto Seguro, Bahia, Brazil), using artificial substrate units, were exposed to a control pH (ambient seawater) and to three levels of seawater acidification (pH reductions of 0.3, 0.6, and 0.9 units below ambient) and collected after 15 and 30 d. After 30 d of exposure, major changes in the structure of the meiofauna community were observed in response to reduced pH. The major meiofauna groups showed divergent responses to acidification. Harpacticoida and Polychaeta densities did not show significant differences due to pH. Nematoda, Ostracoda, Turbellaria, and Tardigrada exhibited their highest densities in low-pH treatments (especially at the pH reduction of 0.6 units, pH 7.5), while harpacticoid nauplii were strongly negatively affected by low pH. This community-based mesocosm study supports previous suggestions that ocean acidification induces important changes in the structure of marine benthic communities. Considering the importance of meiofauna in the food web of coral reef ecosystems, the results presented here demonstrate that the trophic functioning of coral reefs is seriously threatened by ocean acidification.

Fiber-based modeling of in situ ankle ligaments with consideration of progressive failure.

PubMed

Nie, Bingbing; Forman, Jason L; Panzer, Matthew B; Mait, Alexander R; Donlon, John-Paul; Kent, Richard W

2017-08-16

Ligament sprains account for a majority of injuries to the foot and ankle complex among athletic populations. The infeasibility of measuring the in situ response and load paths of individual ligaments has precluded a complete characterization of their mechanical behavior via experiment. In the present study a fiber-based modeling approach of in situ ankle ligaments was developed and validated for determining the heterogeneous force-elongation characteristics and the consequent injury patterns. Nine major ankle ligaments were modeled as bundles of discrete elements, corresponding functionally to the structure of collagen fibers. To incorporate the progressive nature of ligamentous injury, the limit strain at the occurrence of fiber failure was described by a distribution function ranging from 12% to 18% along the width of the insertion site. The model was validated by comparing the structural kinetic and kinematic response obtained experimentally and computationally under well-controlled foot rotations. The simulation results replicated the 6 degree-of-freedom bony motion and ligamentous injuries and, by implication, the in situ deformations of the ligaments. Gross stiffness of the whole ligament derived from the fibers was comparable to existing experimental data. The present modeling approach provides a biomechanically realistic, interpretable and computationally efficient way to characterize the in situ ligament slack, sequential and heterogeneous uncrimping of collagen fascicles and failure propagation as the external load is applied. Applications of this model include functional ankle joint mechanics, injury prevention and countermeasure design for athletes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

PubMed Central

Burgos-Robles, Anthony; Kimchi, Eyal Y.; Izadmehr, Ehsan M.; Porzenheim, Mary Jane; Ramos-Guasp, William A.; Nieh, Edward H.; Felix-Ortiz, Ada C.; Namburi, Praneeth; Leppla, Christopher A.; Presbrey, Kara N.; Anandalingam, Kavitha K.; Pagan-Rivera, Pablo A.; Anahtar, Melodi; Beyeler, Anna; Tye, Kay M.

2017-01-01

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral amygdala (BLA) and prelimbic (PL) medial prefrontal cortex (mPFC) have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally-connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task where in shock- and sucrose-predictive cues were simultaneously presented to induce competition. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, the majority of optogenetically-identified PL-projecting BLA neurons recorded encoded the shock-associated cue, and more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally, BLA→PL photostimulation increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. The BLA→PL circuit plays a critical role in governing the selection of behavioral responses in the face of competing signals. PMID:28436980

Laboratory Testing of Demand-Response Enabled Household Appliances

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

Sparn, B.; Jin, X.; Earle, L.

2013-10-01

With the advent of the Advanced Metering Infrastructure (AMI) systems capable of two-way communications between the utility's grid and the building, there has been significant effort in the Automated Home Energy Management (AHEM) industry to develop capabilities that allow residential building systems to respond to utility demand events by temporarily reducing their electricity usage. Major appliance manufacturers are following suit by developing Home Area Network (HAN)-tied appliance suites that can take signals from the home's 'smart meter,' a.k.a. AMI meter, and adjust their run cycles accordingly. There are numerous strategies that can be employed by household appliances to respond tomore » demand-side management opportunities, and they could result in substantial reductions in electricity bills for the residents depending on the pricing structures used by the utilities to incent these types of responses.The first step to quantifying these end effects is to test these systems and their responses in simulated demand-response (DR) conditions while monitoring energy use and overall system performance.« less

Laboratory Testing of Demand-Response Enabled Household Appliances

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

Sparn, B.; Jin, X.; Earle, L.

2013-10-01

With the advent of the Advanced Metering Infrastructure (AMI) systems capable of two-way communications between the utility's grid and the building, there has been significant effort in the Automated Home Energy Management (AHEM) industry to develop capabilities that allow residential building systems to respond to utility demand events by temporarily reducing their electricity usage. Major appliance manufacturers are following suit by developing Home Area Network (HAN)-tied appliance suites that can take signals from the home's 'smart meter,' a.k.a. AMI meter, and adjust their run cycles accordingly. There are numerous strategies that can be employed by household appliances to respond tomore » demand-side management opportunities, and they could result in substantial reductions in electricity bills for the residents depending on the pricing structures used by the utilities to incent these types of responses. The first step to quantifying these end effects is to test these systems and their responses in simulated demand-response (DR) conditions while monitoring energy use and overall system performance.« less

High-resolution Imaging of Neural Anatomy and Pathology of the Neck.

PubMed

Lee, Jeong Hyun; Cheng, Kai-Lung; Choi, Young Jun; Baek, Jung Hwan

2017-01-01

The neck has intricately connected neural structures, including cervical and brachial plexi, the sympathetic system, lower cranial nerves, and their branches. Except for brachial plexus, there has been little research regarding the normal imaging appearance or corresponding pathologies of neural structures in the neck. The development in imaging techniques with better spatial resolution and signal-to-noise ratio has made it possible to see many tiny nerves to predict complications related to image-guided procedures and to better assess treatment response, especially in the management of oncology patients. The purposes of this review is to present imaging-based anatomy of major nerves in the neck and explain their relevant clinical significance according to representative pathologies of regarded nerves in the neck.

Low-angle normal faulting and isostatic response in the Gulf of Suez: Evidence from seismic interpretation and geometric reconstruction

NASA Technical Reports Server (NTRS)

Perry, S. K.; Schamel, S.

1985-01-01

Tectonic extension within continental crust creates a variety of major features best classed as extensional orogens. These features have come under increasing attention in recent years, with the welding of field observation and theoretical concepts. Most recent advances have come from the Basin and Range Province of the southwestern United States and from the North Sea. Application of these geometric and isostatic concepts, in combination with seismic interpretation, to the southern Gulf of Suez, an active extensional orogen, allows generation of detailed structural maps and geometrically balanced sections which suggest a regional structural model. Geometric models which should prove to be a valuable adjunct to numerical and thermal models for the rifting process are discussed.

Linear and nonlinear Fano resonance in the main chain-structure of additional defects with an isolated ring composed of defects

NASA Astrophysics Data System (ADS)

Ding, Xiu-Huan; Wang, Rui; Qiao, Qian; Zhang, Cun-Xi

2018-03-01

As is well known, Fano resonance originates from the interference between a continuum energy band and an embedded discrete energy level. We study transmission properties of the discrete chain-structure of additional defects with an isolated ring composed of N defect states, and obtain the analytical transmission coefficient of similar Fano formula. Using the formula, we reveal conditions for perfect reflections and transmissions due to either destructive or constructive interferences. It is found that a nonlinear Kerr-like response leads to bistable transmission, and for either linear cases or nonlinear ones, the defects in main arrays have a major impact on perfect reflections, but has no effect on perfect transmission.

Reduction of a linear complex model for respiratory system during Airflow Interruption.

PubMed

Jablonski, Ireneusz; Mroczka, Janusz

2010-01-01

The paper presents methodology of a complex model reduction to its simpler version - an identifiable inverse model. Its main tool is a numerical procedure of sensitivity analysis (structural and parametric) applied to the forward linear equivalent designed for the conditions of interrupter experiment. Final result - the reduced analog for the interrupter technique is especially worth of notice as it fills a major gap in occlusional measurements, which typically use simple, one- or two-element physical representations. Proposed electrical reduced circuit, being structural combination of resistive, inertial and elastic properties, can be perceived as a candidate for reliable reconstruction and quantification (in the time and frequency domain) of dynamical behavior of the respiratory system in response to a quasi-step excitation by valve closure.

Comparative analysis of CDPK family in maize, Arabidopsis, rice and sorghum revealed potential targets for drought tolerance improvement

NASA Astrophysics Data System (ADS)

Mittal, Shikha; Mallikarjuna, Mallana Gowdra; Rao, Atmakuri R.; Jain, Prashant A.; Dash, Prasanta K.; Thirunavukkarasu, Nepolean

2017-12-01

Calcium dependent protein kinases (CDPKs) play major role in regulation of plant growth and development in response to various stresses including drought. A set of 32 CDPK genes identified in maize were further used for searching of orthologs in the model plant Arabidopsis (72) and major food crops such as rice (78) and sorghum (91). We comprehensively investigated the phylogenetic relationship, annotations, gene duplications, gene structure, divergence time, 3-D protein structures and tissue-specific drought induced expression of CDPK genes in all four species. Variation in intron frequency among these species likely contributed to the functional diversity of CDPK genes to various stress responses. Protein kinase and protein kinase C phosphorylation site domains were the most conserved motifs identified in all species. Four groups were identified from the sequence-based phylogenetic analysis, in which maize CDPKs were clustered in group III. The time of divergence (Ka/Ks) analysis revealed that the CDPKs were evolved through stabilizing selection. Expression data showed that the CDPK genes were highly expressed in leaf of maize, rice, and sorghum whereas in Arabidopsis the maximum expression was observed in root. 3-D protein structure were predicted for the nine genes (Arabidopsis: 2, maize: 2, rice: 3 and sorghum: 2) showing differential expression in at least three species. The predicted 3-D structures were further evaluated and validated by Ramachandran plot, ANOLEA, ProSA and Verify-3D. The superimposed 3-D structure of drought-related orthologous proteins retained similar folding pattern owing to their conserved nature. Functional annotation revealed the involvement of CDPK genes in various pathways such as osmotic homeostasis, cell protection and root growth. The interactions of CDPK genes in various pathways play crucial role in imparting drought tolerance through different ABA and MAPK signalling cascades. Our studies suggest that these selected candidate genes could be targeted in development of drought tolerant cultivars in maize, rice and sorghum through appropriate breeding approaches. Our comparative experiments of CDPK genes could also be extended in the drought stress breeding programmes of the related species.

A comparison of phenotypic variation and covariation patterns and the role of phylogeny, ecology, and ontogeny during cranial evolution of new world monkeys.

PubMed

Marroig, G; Cheverud, J M

2001-12-01

Similarity of genetic and phenotypic variation patterns among populations is important for making quantitative inferences about past evolutionary forces acting to differentiate populations and for evaluating the evolution of relationships among traits in response to new functional and developmental relationships. Here, phenotypic co variance and correlation structure is compared among Platyrrhine Neotropical primates. Comparisons range from among species within a genus to the superfamily level. Matrix correlation followed by Mantel's test and vector correlation among responses to random natural selection vectors (random skewers) were used to compare correlation and variance/covariance matrices of 39 skull traits. Sampling errors involved in matrix estimates were taken into account in comparisons using matrix repeatability to set upper limits for each pairwise comparison. Results indicate that covariance structure is not strictly constant but that the amount of variance pattern divergence observed among taxa is generally low and not associated with taxonomic distance. Specific instances of divergence are identified. There is no correlation between the amount of divergence in covariance patterns among the 16 genera and their phylogenetic distance derived from a conjoint analysis of four already published nuclear gene datasets. In contrast, there is a significant correlation between phylogenetic distance and morphological distance (Mahalanobis distance among genus centroids). This result indicates that while the phenotypic means were evolving during the last 30 millions years of New World monkey evolution, phenotypic covariance structures of Neotropical primate skulls have remained relatively consistent. Neotropical primates can be divided into four major groups based on their feeding habits (fruit-leaves, seed-fruits, insect-fruits, and gum-insect-fruits). Differences in phenotypic covariance structure are correlated with differences in feeding habits, indicating that to some extent changes in interrelationships among skull traits are associated with changes in feeding habits. Finally, common patterns and levels of morphological integration are found among Platyrrhine primates, suggesting that functional/developmental integration could be one major factor keeping covariance structure relatively stable during evolutionary diversification of South American monkeys.

Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein E2 recognized by broadly neutralizing antibodies.

PubMed

Meola, Annalisa; Tarr, Alexander W; England, Patrick; Meredith, Luke W; McClure, C Patrick; Foung, Steven K H; McKeating, Jane A; Ball, Jonathan K; Rey, Felix A; Krey, Thomas

2015-02-01

Neutralizing antibodies (NAbs) targeting glycoprotein E2 are important for the control of hepatitis C virus (HCV) infection. One conserved antigenic site (amino acids 412 to 423) is disordered in the reported E2 structure, but a synthetic peptide mimicking this site forms a β-hairpin in complex with three independent NAbs. Our structure of the same peptide in complex with NAb 3/11 demonstrates a strikingly different extended conformation. We also show that residues 412 to 423 are essential for virus entry but not for E2 folding. Together with the neutralizing capacity of the 3/11 Fab fragment, this indicates an unexpected structural flexibility within this epitope. NAbs 3/11 and AP33 (recognizing the extended and β-hairpin conformations, respectively) display similar neutralizing activities despite converse binding kinetics. Our results suggest that HCV utilizes conformational flexibility as an immune evasion strategy, contributing to the limited immunogenicity of this epitope in patients, similar to the conformational flexibility described for other enveloped and nonenveloped viruses. Approximately 180 million people worldwide are infected with hepatitis C virus (HCV), and neutralizing antibodies play an important role in controlling the replication of this major human pathogen. We show here that one of the most conserved antigenic sites within the major glycoprotein E2 (amino acids 412 to 423), which is disordered in the recently reported crystal structure of an E2 core fragment, can adopt different conformations in the context of the infectious virus particle. Recombinant Fab fragments recognizing different conformations of this antigenic site have similar neutralization activities in spite of converse kinetic binding parameters. Of note, an antibody response targeting this antigenic region is less frequent than those targeting other more immunogenic regions in E2. Our results suggest that the observed conformational flexibility in this conserved antigenic region contributes to the evasion of the humoral host immune response, facilitating chronicity and the viral spread of HCV within an infected individual. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structure and transcriptional regulation of the major intrinsic protein gene family in grapevine.

PubMed

Wong, Darren Chern Jan; Zhang, Li; Merlin, Isabelle; Castellarin, Simone D; Gambetta, Gregory A

2018-04-11

The major intrinsic protein (MIP) family is a family of proteins, including aquaporins, which facilitate water and small molecule transport across plasma membranes. In plants, MIPs function in a huge variety of processes including water transport, growth, stress response, and fruit development. In this study, we characterize the structure and transcriptional regulation of the MIP family in grapevine, describing the putative genome duplication events leading to the family structure and characterizing the family's tissue and developmental specific expression patterns across numerous preexisting microarray and RNAseq datasets. Gene co-expression network (GCN) analyses were carried out across these datasets and the promoters of each family member were analyzed for cis-regulatory element structure in order to provide insight into their transcriptional regulation. A total of 29 Vitis vinifera MIP family members (excluding putative pseudogenes) were identified of which all but two were mapped onto Vitis vinifera chromosomes. In this study, segmental duplication events were identified for five plasma membrane intrinsic protein (PIP) and four tonoplast intrinsic protein (TIP) genes, contributing to the expansion of PIPs and TIPs in grapevine. Grapevine MIP family members have distinct tissue and developmental expression patterns and hierarchical clustering revealed two primary groups regardless of the datasets analyzed. Composite microarray and RNA-seq gene co-expression networks (GCNs) highlighted the relationships between MIP genes and functional categories involved in cell wall modification and transport, as well as with other MIPs revealing a strong co-regulation within the family itself. Some duplicated MIP family members have undergone sub-functionalization and exhibit distinct expression patterns and GCNs. Cis-regulatory element (CRE) analyses of the MIP promoters and their associated GCN members revealed enrichment for numerous CREs including AP2/ERFs and NACs. Combining phylogenetic analyses, gene expression profiling, gene co-expression network analyses, and cis-regulatory element enrichment, this study provides a comprehensive overview of the structure and transcriptional regulation of the grapevine MIP family. The study highlights the duplication and sub-functionalization of the family, its strong coordinated expression with genes involved in growth and transport, and the putative classes of TFs responsible for its regulation.

Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage

NASA Astrophysics Data System (ADS)

Kearns, Sarah; Das, Moumita

2015-03-01

We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings.

Signatures of Value Comparison in Ventral Striatum Neurons

PubMed Central

Strait, Caleb E.; Sleezer, Brianna J.; Hayden, Benjamin Y.

2015-01-01

The ventral striatum (VS), like its cortical afferents, is closely associated with processing of rewards, but the relative contributions of striatal and cortical reward systems remains unclear. Most theories posit distinct roles for these structures, despite their similarities. We compared responses of VS neurons to those of ventromedial prefrontal cortex (vmPFC) Area 14 neurons, recorded in a risky choice task. Five major response patterns observed in vmPFC were also observed in VS: (1) offer value encoding, (2) value difference encoding, (3) preferential encoding of chosen relative to unchosen value, (4) a correlation between residual variance in responses and choices, and (5) prominent encoding of outcomes. We did observe some differences as well; in particular, preferential encoding of the chosen option was stronger and started earlier in VS than in vmPFC. Nonetheless, the close match between vmPFC and VS suggests that cortex and its striatal targets make overlapping contributions to economic choice. PMID:26086735

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist.

PubMed

Sanchez, Elisa; Huse, Morgan

2018-04-25

T lymphocytes engage in rapid, polarized signaling, occurring within minutes following TCR activation. This induces formation of the immunological synapse, a stereotyped cell-cell junction that regulates T cell activation and directionally targets effector responses. To study these processes effectively, an imaging approach that is tailored to capturing fast, polarized responses is necessary. This protocol describes such a system, which is based on a photoactivatable peptide-major histocompatibility complex (pMHC) that is non-stimulatory until it is exposed to ultraviolet light. Targeted decaging of this reagent during videomicroscopy experiments enables precise spatiotemporal control of TCR activation and high-resolution monitoring of subsequent cellular responses by total internal reflection (TIRF) imaging. This approach is also compatible with genetic and pharmacological perturbation strategies. This allows for the assembly of well-defined molecular pathways that link TCR signaling to the formation of the polarized cytoskeletal structures that underlie the immunological synapse.

Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus.

PubMed

Pizzolla, Angela; Smith, Jeffery M; Brooks, Andrew G; Reading, Patrick C

2017-04-01

Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity. Therefore, a number of approaches have been developed to target specific PRRs in an effort to stimulate innate immunity and reduce disease in a variety of settings, including during influenza infections. Herein, we discuss progress in immunomodulation strategies designed to target cell-associated PRRs of the innate immune system, thereby, modifying innate responses to IAV infection and/or augmenting immune responses to influenza vaccines. © Society for Leukocyte Biology.

Crystal Structures of Aedes Aegypt Alanine Glyoxylate Aminotransferase

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

Han,Q.; Robinson, H.; Gao, Y.

Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75{angstrom} high-resolution three-dimensional crystal structure of AGT from themore » mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1{angstrom} resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.« less

Density effect on great tit (Parus major) clutch size intensifies in a polluted environment.

PubMed

Eeva, Tapio; Lehikoinen, Esa

2013-12-01

Long-term data on a great tit (Parus major) population breeding in a metal-polluted zone around a copper-nickel smelter indicate that, against expectations, the clutch size of this species is decreasing even though metal emissions in the area have decreased considerably over the past two decades. Here, we document long-term population-level changes in the clutch size of P. major and explore if changes in population density, population numbers of competing species, timing of breeding, breeding habitat, or female age distribution can explain decreasing clutch sizes. Clutch size of P. major decreased by one egg in the polluted zone during the past 21 years, while there was no significant change in clutch size in the unpolluted reference zone over this time period. Density of P. major nests was similar in both environments but increased threefold during the study period in both areas (from 0.8 to 2.4 nest/ha). In the polluted zone, clutch size has decreased as a response to a considerable increase in population density, while a corresponding density change in the unpolluted zone did not have such an effect. The other factors studied did not explain the clutch size trend. Fledgling numbers in the polluted environment have been relatively low since the beginning of the study period, and they do not show a corresponding decrease to that noted for the clutch size over the same time period. Our study shows that responses of commonly measured life-history parameters to anthropogenic pollution depend on the structure of the breeding population. Interactions between pollution and intrinsic population characters should therefore be taken into account in environmental studies.

Brain structural plasticity in survivors of a major earthquake

PubMed Central

Lui, Su; Chen, Long; Yao, Li; Xiao, Yuan; Wu, Qi-Zhu; Zhang, Jun-Ran; Huang, Xiao-Qi; Zhang, Wei; Wang, Yu-Qin; Chen, Hua-Fu; Chan, Raymond C.K.; Sweeney, John A.; Gong, Qi-Yong

2013-01-01

Background Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. Methods Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13–25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. Results We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). Limitations Differences in the variance of survivor and control data could impact study findings. Conclusion Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal–limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal. PMID:23710694

The changing relationships between academic health centers and their universities: a look at the University of Pennsylvania.

PubMed

Phillips, Susan E; Rubenstein, Arthur H

2008-09-01

After a period of financial losses in the University of Pennsylvania Health System stemming from a combination of internal decision making and negative external market forces, the university set out to make substantial changes in the governance and administrative organization overseeing its health system and medical school. The changes were designed to assure the university and its trustees that financial controls were strengthened and that the missions of research, education, and patient care were balanced. The governance changes included creating a structure whereby a single administrative leader was responsible for all three missions--education, research, and clinical care--and reported directly to the president of the university. Further, existing governing boards responsible for various entities within the school of medicine and health system were disbanded, and a new single board was created to oversee PENN Medicine, the overarching organization established in 2001 and now responsible for oversight of the University of Pennsylvania School of Medicine and the University of Pennsylvania Health System. The realignment initiated by these major changes spawned additional refinements in leadership responsibilities and process controls that, together with the new governance model, are credited with financial recovery and stronger performance in all aspects of the enterprise. These structural changes led to greater emphasis on integrating and coordinating programs to take advantage of PENN Medicine's home in a leading university.

Mechanotransduction through Cytoskeleton

NASA Technical Reports Server (NTRS)

Ingber, Donald

2002-01-01

The goal of this project was to characterize the molecular mechanism by which cells recognize and respond to physical forces in their local environment. The project was based on the working hypothesis that cells sense mechanical stresses, such as those due to gravity, through their cell surface adhesion receptors (e.g., integrins) and that they respond as a result of structural arrangements with their internal cytoskeleton (CSK) which are orchestrated through use of tensegrity architecture. In this project, we carried out studies to define the architectural and molecular basis of cellular mechanotransduction. Our major goal was to define the molecular pathway that mediates mechanical force transfer between integrins and the CSK and to determine how mechanical deformation of integrin-CSK linkages is transduced into a biochemical response. Elucidation of the mechanism by which cells sense mechanical stresses through integrins and translate them into a biochemical response should help us to understand the molecular basis of the cellular response to gravity as well as many other forms of mechanosensation and tissue regulation. The specific aims of this proposal were: 1. To define the molecular basis of mechanical coupling between integrins, vinculin, and the actin CSK; 2. To develop a computer simulation of how mechanical stresses alter CSK structure and test this model in living cells; 3. To determine how mechanical deformation of integrin-CSK linkages is transduced into a biochemical response.

Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data.

PubMed

Redlich, Ronny; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Zaremba, Dario; Bürger, Christian; Münker, Sandra; Mühlmann, Lisa; Wahl, Patricia; Heindel, Walter; Arolt, Volker; Alferink, Judith; Zwanzger, Peter; Zavorotnyy, Maxim; Kugel, Harald; Dannlowski, Udo

2016-06-01

Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified. To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response. In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21). Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes. One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = -18; Z score, 4.00; P < .001; peak voxel r = 0.73). Furthermore, the analysis of treatment effects revealed a increase in hippocampal volume in the ECT sample (MNI coordinates x = -28, y = -9, z = -18; Z score, 7.81; P < .001) that was missing in the medication-only sample. A relatively small degree of structural impairment in the subgenual cingulate cortex before therapy seems to be associated with successful treatment with ECT. In the future, neuroimaging techniques could prove to be promising tools for predicting the individual therapeutic effectiveness of ECT.

Towards Coupling of Macroseismic Intensity with Structural Damage Indicators

NASA Astrophysics Data System (ADS)

Kouteva, Mihaela; Boshnakov, Krasimir

2016-04-01

Knowledge on basic data of ground motion acceleration time histories during earthquakes is essential to understanding the earthquake resistant behaviour of structures. Peak and integral ground motion parameters such as peak ground motion values (acceleration, velocity and displacement), measures of the frequency content of ground motion, duration of strong shaking and various intensity measures play important roles in seismic evaluation of existing facilities and design of new systems. Macroseismic intensity is an earthquake measure related to seismic hazard and seismic risk description. Having detailed ideas on the correlations between the earthquake damage potential and macroseismic intensity is an important issue in engineering seismology and earthquake engineering. Reliable earthquake hazard estimation is the major prerequisite to successful disaster risk management. The usage of advanced earthquake engineering approaches for structural response modelling is essential for reliable evaluation of the accumulated damages in the existing buildings and structures due to the history of seismic actions, occurred during their lifetime. Full nonlinear analysis taking into account single event or series of earthquakes and the large set of elaborated damage indices are suitable contemporary tools to cope with this responsible task. This paper presents some results on the correlation between observational damage states, ground motion parameters and selected analytical damage indices. Damage indices are computed on the base of nonlinear time history analysis of test reinforced structure, characterising the building stock of the Mediterranean region designed according the earthquake resistant requirements in mid XX-th century.

U-shaped micro-groove fiber based on femtosecond laser processing for humidity sensing

NASA Astrophysics Data System (ADS)

Fu, Gui; Ma, Li-li; Su, Fu-fang; Shi, Meng

2018-05-01

A novel optical fiber sensor with a U-shaped micro-groove structure ablated by femtosecond laser on single-mode fiber for measuring air relative humidity (RH) is reported in this paper. In order to improve the accuracy of sensor, a graphene oxide (GO)/polyvinyl alcohol (PVA) composite film is coated on the surface of micro-groove structure. In the U-shaped micro-groove structure, the remaining core and micro-cavity in the micro-groove make up two major optical propagation paths, forming a Mach-Zehnder interferometer (MZI). The sensor has a good linear response within the RH range of 30%—85%, and the maximum sensitivity can reach 0.638 1 nm/%RH. The effect of temperature on the overall performance of the humidity sensor is also investigated. As a new type of all-fiber device, the sensor shows excellent sensitivity and stability.

Structure of Ljungan virus provides insight into genome packaging of this picornavirus

NASA Astrophysics Data System (ADS)

Zhu, Ling; Wang, Xiangxi; Ren, Jingshan; Porta, Claudine; Wenham, Hannah; Ekström, Jens-Ola; Panjwani, Anusha; Knowles, Nick J.; Kotecha, Abhay; Siebert, C. Alistair; Lindberg, A. Michael; Fry, Elizabeth E.; Rao, Zihe; Tuthill, Tobias J.; Stuart, David I.

2015-10-01

Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly poorly studied group within this family are those that lack the internal coat protein, VP4. Here we report the atomic structure of one such virus, Ljungan virus, the type member of the genus Parechovirus B, which has been linked to diabetes and myocarditis in humans. The 3.78-Å resolution cryo-electron microscopy structure shows remarkable features, including an extended VP1 C terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N terminus of VP3, binding to which orders some 12% of the viral genome. This apparently charge-driven RNA attachment suggests that this branch of the picornaviruses uses a different mechanism of genome encapsidation, perhaps explored early in the evolution of picornaviruses.

Study of Acoustic Emissions from Composites

NASA Technical Reports Server (NTRS)

Walker, James L.; Workman, Gary L.

1997-01-01

The nondestructive evaluation (NDE) of future propulsion systems utilizing advanced composite structures for the storage of cryogenic fuels, such as liquid hydrogen or oxygen, presents many challenges. Economic justification for these structures requires light weight, reusable components with an infrastructure allowing periodic evaluation of structural integrity after enduring demanding stresses during operation. A major focus has been placed on the use of acoustic emission NDE to detect propagating defects, in service, necessitating an extensive study into characterizing the nature of acoustic signal propagation at very low temperatures and developing the methodology of applying AE sensors to monitor cryogenic components. This work addresses the question of sensor performance in the cryogenic environment. Problems involving sensor mounting, spectral response and durability are addressed. The results of this work provides a common point of measure from which sensor selection can be made when testing composite components at cryogenic temperatures.

Aquarium Microbiome Response to Ninety-Percent System Water Change: Clues to Microbiome Management

PubMed Central

Van Bonn, William; LaPointe, Allen; Gibbons, Sean M.; Frazier, Angel; Hampton-Marcell, Jarrad; Gilbert, Jack

2016-01-01

The bacterial community composition and structure of water from an established teleost fish system was examined before, during and after a major water change to explore the impact of such a water-change disturbance on the stability of the aquarium water microbiome. The diversity and evenness of the bacterial community significantly increased following the 90% water replacement. While the change in bacterial community structure was significant, it was slight, and was also weakly correlated with changes in physicochemical parameters. Interestingly there was a significant shift in the correlative network relationships between operational taxonomic units from before to after the water replacement. We suggest this shift in network structure is due to the turnover of many taxa during the course of water replacement. These observations will inform future studies into manipulation of the microbiome by changing system environmental parameter values to optimize resident animal health. PMID:26031788

Structure of Ljungan virus provides insight into genome packaging of this picornavirus.

PubMed

Zhu, Ling; Wang, Xiangxi; Ren, Jingshan; Porta, Claudine; Wenham, Hannah; Ekström, Jens-Ola; Panjwani, Anusha; Knowles, Nick J; Kotecha, Abhay; Siebert, C Alistair; Lindberg, A Michael; Fry, Elizabeth E; Rao, Zihe; Tuthill, Tobias J; Stuart, David I

2015-10-08

Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly poorly studied group within this family are those that lack the internal coat protein, VP4. Here we report the atomic structure of one such virus, Ljungan virus, the type member of the genus Parechovirus B, which has been linked to diabetes and myocarditis in humans. The 3.78-Å resolution cryo-electron microscopy structure shows remarkable features, including an extended VP1 C terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N terminus of VP3, binding to which orders some 12% of the viral genome. This apparently charge-driven RNA attachment suggests that this branch of the picornaviruses uses a different mechanism of genome encapsidation, perhaps explored early in the evolution of picornaviruses.

The Structured Interview and Interviewer Training in the Admissions Process

PubMed Central

Cox, Wendy C.; White-Harris, Carla; Blalock, Susan J.

2007-01-01

Objectives To determine the extent to which the structured interview is used in the PharmD admissions process in US colleges and schools of pharmacy, and the prevalence and content of interviewer training. Methods A survey instrument consisting of 7 questions regarding interviews and interviewer training was sent to 92 colleges and schools of pharmacy in the United States that were accredited or seeking accreditation. Results Sixty survey instruments (65% response rate) were returned. The majority of the schools that responded (80%) used interviews as part of the PharmD admissions process. Of the schools that used an interview as part of the admissions process, 86% provided some type of interviewer training and 13% used a set of predefined questions in admissions interviews. Conclusions Most colleges and schools of pharmacy use some components of the structured interview in the PharmD admissions process; however, training for interviewers varies widely among colleges and schools of pharmacy. PMID:17998980

The self-concept and conjugal loss: evidence for structural change.

PubMed

Montpetit, Mignon A; Bergeman, C S; Bisconti, Toni L

2010-08-01

The self-concept is often considered to be a personal resource that individuals may use to cope with life stressors, but little is known about how this entity might itself change in response to profound stress. The present study examines structural change in self-concept following conjugal loss in later life. Analyses were conducted on data collected from 57 widows every 4 months over the first 2 years post-loss. The first objective was to explore the adequacy of an operational definition of the self-concept as a latent construct lying at the confluence of self-esteem, perceived environmental mastery, and optimism. Because confirmatory factor analysis (CFA) supported this theoretically based conceptualization, the second objective of the study was to model stability and change in the structure of the self-concept over the 2-year study period. Results suggested that there is both stability and change in the self-system during the adjustment to major life stress.

Aquarium microbiome response to ninety-percent system water change: Clues to microbiome management.

PubMed

Van Bonn, William; LaPointe, Allen; Gibbons, Sean M; Frazier, Angel; Hampton-Marcell, Jarrad; Gilbert, Jack

2015-01-01

The bacterial community composition and structure of water from an established teleost fish system was examined before, during and after a major water change to explore the impact of such a water-change disturbance on the stability of the aquarium water microbiome. The diversity and evenness of the bacterial community significantly increased following the 90% water replacement. While the change in bacterial community structure was significant, it was slight, and was also weakly correlated with changes in physicochemical parameters. Interestingly there was a significant shift in the correlative network relationships between operational taxonomic units from before to after the water replacement. We suggest this shift in network structure is due to the turnover of many taxa during the course of water replacement. These observations will inform future studies into manipulation of the microbiome by changing system environmental parameter values to optimize resident animal health. © 2015 Wiley Periodicals, Inc.

Lubrication mechanisms of hollow-core inorganic fullerene-like nanoparticles: coupling experimental and computational works

NASA Astrophysics Data System (ADS)

Lahouij, I.; Bucholz, E. W.; Vacher, B.; Sinnott, S. B.; Martin, J. M.; Dassenoy, F.

2012-09-01

Inorganic fullerene-like (IF) nanoparticles made of metal dichalcogenides have previously been recognized to be good friction modifiers and anti-wear additives under boundary lubrication conditions. The tribological performance of these particles appears to be a result of their size, structure and morphology, along with the test conditions. However, the very small scale of the IF nanoparticles makes distinguishing the properties which affect the lubrication mechanism exceedingly difficult. In this work, a high resolution transmission electron microscope equipped with a nanoindentation holder is used to manipulate individual hollow IF-WS2 nanoparticles and to investigate their responses to compression. Additional atomistic molecular dynamics (MD) simulations of similarly structured, individual hollow IF-MoS2 nanoparticles are performed for compression studies between molybdenum surfaces on their major and minor axis diameters. MD simulations of these structures allows for characterization of the influence of structural orientation on the mechanical behavior and nano-sheet exfoliation of hollow-core IF nanoparticles. The experimental and theoretical results for these similar nanoparticles are qualitatively compared.

Lubrication mechanisms of hollow-core inorganic fullerene-like nanoparticles: coupling experimental and computational works.

PubMed

Lahouij, I; Bucholz, E W; Vacher, B; Sinnott, S B; Martin, J M; Dassenoy, F

2012-09-21

Inorganic fullerene-like (IF) nanoparticles made of metal dichalcogenides have previously been recognized to be good friction modifiers and anti-wear additives under boundary lubrication conditions. The tribological performance of these particles appears to be a result of their size, structure and morphology, along with the test conditions. However, the very small scale of the IF nanoparticles makes distinguishing the properties which affect the lubrication mechanism exceedingly difficult. In this work, a high resolution transmission electron microscope equipped with a nanoindentation holder is used to manipulate individual hollow IF-WS(2) nanoparticles and to investigate their responses to compression. Additional atomistic molecular dynamics (MD) simulations of similarly structured, individual hollow IF-MoS(2) nanoparticles are performed for compression studies between molybdenum surfaces on their major and minor axis diameters. MD simulations of these structures allows for characterization of the influence of structural orientation on the mechanical behavior and nano-sheet exfoliation of hollow-core IF nanoparticles. The experimental and theoretical results for these similar nanoparticles are qualitatively compared.

Comparative analysis of the mechanical signals in lung development and compensatory growth.

PubMed

Hsia, Connie C W

2017-03-01

This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs.

Comparative Analysis of the Mechanical Signals in Lung Development and Compensatory Growth

PubMed Central

Hsia, Connie C.W.

2017-01-01

This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax, and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships, and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling, may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences, and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs. PMID:28084523

Virus-based Photo-Responsive Nanowires Formed By Linking Site-Directed Mutagenesis and Chemical Reaction

NASA Astrophysics Data System (ADS)

Murugesan, Murali; Abbineni, Gopal; Nimmo, Susan L.; Cao, Binrui; Mao, Chuanbin

2013-05-01

Owing to the genetic flexibility and error-free bulk production, bio-nanostructures such as filamentous phage showed great potential in materials synthesis, however, their photo-responsive behaviour is neither explored nor unveiled. Here we show M13 phage genetically engineered with tyrosine residues precisely fused to the major coat protein is converted into a photo-responsive organic nanowire by a site-specific chemical reaction with an aromatic amine to form an azo dye structure on the surface. The resulting azo-M13-phage nanowire exhibits reversible photo-responsive properties due to the photo-switchable cis-trans isomerisation of the azo unit formed on the phage. This result shows that site-specific display of a peptide on bio-nanostructures through site-directed genetic mutagenesis can be translated into site-directed chemical reaction for developing advanced materials. The photo-responsive properties of the azo-M13-phage nanowires may open the door for the development of light controllable smart devices for use in non-linear optics, holography data storage, molecular antenna, and actuators.

Virus-based Photo-Responsive Nanowires Formed By Linking Site-Directed Mutagenesis and Chemical Reaction

PubMed Central

Murugesan, Murali; Abbineni, Gopal; Nimmo, Susan L.; Cao, Binrui; Mao, Chuanbin

2013-01-01

Owing to the genetic flexibility and error-free bulk production, bio-nanostructures such as filamentous phage showed great potential in materials synthesis, however, their photo-responsive behaviour is neither explored nor unveiled. Here we show M13 phage genetically engineered with tyrosine residues precisely fused to the major coat protein is converted into a photo-responsive organic nanowire by a site-specific chemical reaction with an aromatic amine to form an azo dye structure on the surface. The resulting azo-M13-phage nanowire exhibits reversible photo-responsive properties due to the photo-switchable cis-trans isomerisation of the azo unit formed on the phage. This result shows that site-specific display of a peptide on bio-nanostructures through site-directed genetic mutagenesis can be translated into site-directed chemical reaction for developing advanced materials. The photo-responsive properties of the azo-M13-phage nanowires may open the door for the development of light controllable smart devices for use in non-linear optics, holography data storage, molecular antenna, and actuators. PMID:23673356

Cross-talk between clinical and host-response parameters of periodontitis in smokers.

PubMed

Nagarajan, R; Miller, C S; Dawson, D; Al-Sabbagh, M; Ebersole, J L

2017-06-01

Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host-response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens and oral commensal bacteria; and (iv) other variables of interest, in a population of smokers with (n = 171) and without (n = 117) periodontitis. Bayesian network structured learning (BNSL) techniques were used to investigate potential associations and cross-talk between the four broad sets of variables. BNSL revealed two broad communities with markedly different topology between the populations of smokers, with and without periodontitis. Confidence of the edges in the resulting network also showed marked variations within and between the periodontitis and nonperiodontitis groups. The results presented validated known associations and discovered new ones with minimal precedence that may warrant further investigation and novel hypothesis generation. Cross-talk between the clinical variables and antibody profiles of bacteria were especially pronounced in the case of periodontitis and were mediated by the antibody response profile to Porphyromonas gingivalis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transient rheology of stimuli responsive hydrogels: Integrating microrheology and microfluidics

NASA Astrophysics Data System (ADS)

Sato, Jun

Stimuli-responsive hydrogels have diverse potential applications in the field of drug delivery, tissue engineering, agriculture, cosmetics, gene therapy, and as sensors and actuators due to their unique responsiveness to external signals, such as pH, temperature, and ionic strength. Understanding the responsiveness of hydrogel structure and rheology to these stimuli is essential for designing materials with desirable performance. However, no instrumentation and well-defined methodology are available to characterize the structural and rheological responses to rapid solvent changes. In this thesis, a new microrheology set-up is described, which allows us to quantitatively measure the transient rheological properties and microstructure of a variety of solvent-responsive complex fluids. The device was constructed by integrating particle tracking microrheology and microfluidics and offers unique experimental capabilities for performing solvent-reponse measurements on soft fragile materials without applying external shear forces. Transient analysis methods to quantitatively obtain rheological properties were also constructed, and guidelines for the trade-off between statistical validity and temporal resolution were developed to accurately capture physical transitions. Employing the new device and methodology, we successfully quantified the transient rheological and microstructural responses during gel formation and break-up, and viscosity changes of solvent-responsive complex fluids. The analysis method was expanded for heterogeneous samples, incorporating methods to quantify the microrheology of samples with broad distributions of individual particle dynamics. Transient microrheology measurements of fragile, heterogeneous, self-assembled block copolypeptide hydrogels revealed that solvent exchange via convective mixing and dialysis can lead to significantly different gel properties and that commonly applied sample preparation protocols for the characterization of soft biomaterials could lead to erroneous conclusions about microstructural dynamics. Systematic investigations by varying key parameters, like molecular structure, gel concentration, salt concentration, and tracer particle size for microrheology, revealed that subtle variations in molecular architecture can cause major changes in response dynamics. Moreover, the results showed that the method can be applied for studying gel formation and breakup kinetics. The research in this thesis facilitates the design of solvent-responsive soft materials with appropriate microstructural dynamics for in vivo applications like tissue engineering and drug delivery, and can also be applied to study the effect of solvents on self-assembly mechanisms in other responsive soft materials, such as polymer solutions and colloidal dispersions.

Replication Protein A Presents Canonical Functions and Is Also Involved in the Differentiation Capacity of Trypanosoma cruzi

PubMed Central

Pavani, Raphael Souza; da Silva, Marcelo Santos; Fernandes, Carlos Alexandre Henrique; Morini, Flavia Souza; Araujo, Christiane Bezerra; Fontes, Marcos Roberto de Mattos; Sant’Anna, Osvaldo Augusto; Machado, Carlos Renato; Cano, Maria Isabel; Fragoso, Stenio Perdigão; Elias, Maria Carolina

2016-01-01

Replication Protein A (RPA), the major single stranded DNA binding protein in eukaryotes, is composed of three subunits and is a fundamental player in DNA metabolism, participating in replication, transcription, repair, and the DNA damage response. In human pathogenic trypanosomatids, only limited studies have been performed on RPA-1 from Leishmania. Here, we performed in silico, in vitro and in vivo analysis of Trypanosoma cruzi RPA-1 and RPA-2 subunits. Although computational analysis suggests similarities in DNA binding and Ob-fold structures of RPA from T. cruzi compared with mammalian and fungi RPA, the predicted tridimensional structures of T. cruzi RPA-1 and RPA-2 indicated that these molecules present a more flexible tertiary structure, suggesting that T. cruzi RPA could be involved in additional responses. Here, we demonstrate experimentally that the T. cruzi RPA complex interacts with DNA via RPA-1 and is directly related to canonical functions, such as DNA replication and DNA damage response. Accordingly, a reduction of TcRPA-2 expression by generating heterozygous knockout cells impaired cell growth, slowing down S-phase progression. Moreover, heterozygous knockout cells presented a better efficiency in differentiation from epimastigote to metacyclic trypomastigote forms and metacyclic trypomastigote infection. Taken together, these findings indicate the involvement of TcRPA in the metacyclogenesis process and suggest that a delay in cell cycle progression could be linked with differentiation in T. cruzi. PMID:27984589

Research of a real-time overload monitoring and response system of bridges and roads

NASA Astrophysics Data System (ADS)

Yu, Yan; Shi, Yan; Zhao, Xuefeng; Ou, Jinping

2012-04-01

Due to the general overloading of vehicles, premature failure of bridges and roads are more and more obvious. Structural behaviors of engineering structures need real-time monitoring and diagnosis, timely detection of structural damage, evaluation of their safety, and necessary precautions, in order to prevent major accident such as the collapse of bridges and roads. But the existing monitoring system, which is very expensive, does not apply to the low budget structures. Therefore, a potable, low-cost, low-power structural monitoring system, which consists of electric resistance strain gauge, collection and execution unit, graph collection system and analysis software, is designed in this paper. The system can collect the critical data about the force of pavement to take the certain judge algorithm. The alarm will be given and the overburden data will be transmitted to IDC to make the further analysis when the pavement is overburden. At the same time, the plates of overweight vehicles can be collected and sent to the relevant departments. The system has the features of simple structure, easy realization, and low cost, which fills the application gaps in structural health monitoring of low-budget project.

Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α).

PubMed

Giotis, Efstathios S; Robey, Rebecca C; Skinner, Natalie G; Tomlinson, Christopher D; Goodbourn, Stephen; Skinner, Michael A

2016-08-05

Viruses that infect birds pose major threats-to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses H5N1 and H7N9). Controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. The type I interferon-coordinated response constitutes the major antiviral innate defence. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Viruses induce interferon-stimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. This study focusses on the potentially anti-viral genes by identifying those induced just by interferon in primary chick embryo fibroblasts. Three transcriptomic technologies were exploited: RNA-seq, a classical 3'-biased chicken microarray and a high density, "sense target", whole transcriptome chicken microarray, with each recognising 120-150 regulated genes (curated for duplication and incorrect assignment of some microarray probesets). Overall, the results are considered robust because 128 of the compiled, curated list of 193 regulated genes were detected by two, or more, of the technologies.

Construction and expression of immunogenic hybrid enterotoxigenic Escherichia coli CFA/I and CS2 colonization fimbriae for use in vaccines.

PubMed

Tobias, Joshua; Svennerholm, Ann-Mari; Holmgren, Jan; Lebens, Michael

2010-07-01

Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrheal morbidity in developing countries, especially in children and also of traveler's diarrhea. Colonization factors (CFs) of ETEC, like CFA/I and CS2 which are genetically and structurally related, play a substantial role in pathogenicity, and since intestinal-mucosal immune responses against CFs appear to be protective, much effort has focused on the development of a CF-based ETEC vaccine. We have constructed hybrid operons in which the major CS2 subunit-encoding cotA gene was inserted into the CFA/I operon, either replacing (hybrid I) or being added to the major CFA/I subunit-encoding cfaB gene (hybrid II). Using specific monoclonal antibodies against the major subunits of CFA/I and CS2, high levels of surface expression of both fimbrial subunits were shown in E. coli carrying the hybrid II operon. Oral immunization of mice with formalin-killed bacteria expressing hybrid II fimbriae induced strong CFA/I- and CS2-specific serum IgG + IgM and fecal IgA antibody responses, which were higher than those achieved by similar immunization with the reference strains. Bacteria expressing hybrid fimbriae are potential candidate strains in an oral-killed CF-ETEC vaccine, and the approach represents an attractive and novel means of producing a broad-spectrum ETEC vaccine.

Sex differences in event-related risk for major depression.

PubMed

Maciejewski, P K; Prigerson, H G; Mazure, C M

2001-05-01

This study sought to determine if women are more likely than men to experience an episode of major depression in response to stressful life events. Sex differences in event-related risk for depression were examined by means of secondary analyses employing data from the Americans' Changing Lives study. The occurrence and time of occurrence of depression onset and instances of stressful life events within a 12-month period preceding a structured interview were documented in a community-based sample of 1024 men and 1800 women. Survival analytical techniques were used to examine sex differences in risk for depression associated with generic and specific stressful life events. Women were approximately three times more likely than men to experience major depression in response to any stressful life event. Women and men did not differ in risk for depression associated with the death of a spouse or child, events affecting their relationship to a spouse/partner (divorce and marital/love problems) or events corresponding to acute financial or legal difficulties. Women were at elevated risk for depression associated with more distant interpersonal losses (death of a close friend or relative) and other types of events (change of residence, physical attack, or life-threatening illness/injury). Stressful life events overall, with some exceptions among specific event types, pose a greater risk for depression among women compared to men.

Assessment of source of information for polio supplementary immunization activities in 2014 and 2015, Somali, Ethiopia

PubMed Central

Bedada, Selamawit Yilma; Gallagher, Kathleen; Aregay, Aron Kassahun; Mohammed, Bashir; Maalin, Mohammed Adem; Hassen, Hassen Abdisemed; Ali, Yusuf Mohammed; Braka, Fiona; Kilebou, Pierre M’pele

2017-01-01

Introduction Communication is key for the successful implementation of polio vaccination campaigns. The purpose of this study is to review and analyse the sources of information utilized by caregivers during polio supplementary immunization activities (SIAs) in Somali, Ethiopia in 2014 and 2015. Methods Data on sources of information about the polio campaign were collected post campaign from caregivers by trained data collectors as part of house to house independent monitoring. The sources of information analysed in this paper include town criers (via megaphones), health workers, religious leaders, kebele leaders (Kebele is the lowest administrative structure in Ethiopia), radio, television, text message and others. The repetition of these sources of information was analysed across years and zones for trends. Polio vaccination campaign coverage was also reviewed by year and zones within the Somali region in parallel with the major sources of information used in the respective year and zones. 57,745 responses were used for this analysis but the responses were received from < or = 57,745 individuals since some of them may provide more than one response. Moreover, because sampling of households is conducted independently during each round of independent monitoring, the same household may have been included more than once in our analysis. The methodology used for independent monitoring does not allow for the calculation of response rates. Monitors go from house to house until information from 20 households is received. Results From the total 57,745 responses reviewed, over 37% of respondents reported that town criers were their source for information about the 2014 and 2015 polio SIAs. Zonal trends in using town criers as a major source of information in both study years remained consistent except in two zones. 87.5% of zones that reported at least 90% coverage during both study years had utilized town criers as a major source of information while the rest (12.5%) used health workers. Conclusion We found that town criers were consistently the major source of information about the polio campaigns for Somali region parents and caregivers during polio immunization days held in 2014 and 2015. Health workers and kebele leaders were also important sources of information about the polio campaign for parents. PMID:28983395

The Basal Ganglia and Adaptive Motor Control

NASA Astrophysics Data System (ADS)

Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

1994-09-01

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Coxiella burnetii Lipopolysaccharide: What Do We Know?

PubMed Central

Abnave, Prasad; Muracciole, Xavier; Ghigo, Eric

2017-01-01

A small gram-negative bacterium, Coxiella burnetii (C. burnetii), is responsible for a zoonosis called Q fever. C. burnetii is an intracellular bacterium that can survive inside microbicidal cells like monocytes and macrophages by hijacking several functions of the immune system. Among several virulence factors, the lipopolysaccharide (LPS) of C. burnetii is one of the major factors involved in this immune hijacking because of its atypical composition and structure. Thus, the aim of this mini-review is to summarize the repressive effects of C. burnetii LPS on the antibacterial immunity of cells. PMID:29168790

The dynamics of fresh fruit and vegetable pricing in the supermarket channel.

PubMed

McLaughlin, Edward W

2004-09-01

This paper explains the major factors that contribute to the complicated price formation process, as several levels, of fresh fruit and vegetables in the US. Several factors are explored: marketing channels, market structure changes, pricing techniques and promotional impacts, retail responses to supply changes, and price versus value. The paper illustrates with recent examples and research findings that the fresh produce system is dynamic and that simplistic solutions to complex problems are not likely. The paper finishes by suggesting some areas for needed additional research.

Defined contribution defined: health insurance for the next century.

PubMed

Marhula, D C; Shannon, E G

2001-01-01

The consumerism movement will dramatically affect the current payer model and present a new series of challenges for managed care organizations. Employers will fuel the changes, as they create health benefit programs that are modeled after retirement programs. In these cases, employers will shift a major portion of financial responsibility to employees, who will be asked to make buying decisions often previously determined by managed care organizations. New business entities known as health navigators will be formed to aid consumers. However, many structural and policy obstacles may slow or transform the consumerism movement.

Erythrocyte enzymes in groups of Rattus norvegicus with genetic differences in 2,3-diphosphoglycerate levels.

PubMed

Noble, N A; Tanaka, K R

1979-01-01

1. A major locus with two alleles is responsible for large differences in erythrocyte 2,3-diphosphoglycerate (DPG) levels in Rattus norvegicus. Blood from homozygous High-DPG, homozygous Low-DPG and heterozygous animals was used to measure blood indices and red cell enzyme activities. 2. Significant differences between groups were found in DPG levels, white blood cell counts and hemoglobin levels. 3. The results suggest that none of the red cell enzymes assayed is structurally or quantitatively different in the three groups.

Persuasion stage in adoption theory: a cognitive response-cognitive structure assessment of source credibility and tax-incentive effects on consumer decision making for residential solar systems. [Suburbs of Baltimore

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

Batory, S.S.

1981-01-01

The research objective was to learn more about the consumer's acceptance or rejection process toward a major residential energy innovation, a solar-generated water heating system. An experiment was conducted that evaluated one aspect of solar's commercialization, the persuasion stage in new-product-adoption decision making. A test of source credibility and monetary incentive effects on the consumer's decision-making processes was carried out. The experiment contained two message sources: the Department of Energy (a high credibility source) and a homebuilder (a moderate credibility source), and three levels of incentives, a tax credit equal to 40% of the solar unit purchase price, a 20%more » tax credit, and no tax credit. Subjects were randomly assigned to either a control group or one of six experimental treatments in a 2 x 3 fixed-effects factorial design. Subjects were 226 adult homeowners drawn from the suburbs of Baltimore, Maryland. The research postulated and tested a process of acceptance or rejection of innovations which was based on a cognitive-response/cognitive-structure paradigm of decision making. This process is called the persuasion stage by adoption theorists. Cognitive responses, beliefs, attitudes, and behavioral measures were the dependent variables. Consumers were shown to confront or debate incoming information by comparing it to their existing cognitive structure. This comparison process generated cognitive responses which led to changes in beliefs, attitudes, and behavior toward the innovation. The findings confirm that the federal government's intervention in the marketplace is having a favorable effect on the adoption decision process toward solar-generated water heating.« less

Impact of an irregular friction formulation on dynamics of a minimal model for brake squeal

NASA Astrophysics Data System (ADS)

Stender, Merten; Tiedemann, Merten; Hoffmann, Norbert; Oberst, Sebastian

2018-07-01

Friction-induced vibrations are of major concern in the design of reliable, efficient and comfortable technical systems. Well-known examples for systems susceptible to self-excitation can be found in fluid structure interaction, disk brake squeal, rotor dynamics, hip implants noise and many more. While damping elements and amplitude reduction are well-understood in linear systems, nonlinear systems and especially self-excited dynamics still constitute a challenge for damping element design. Additionally, complex dynamical systems exhibit deterministic chaotic cores which add severe sensitivity to initial conditions to the system response. Especially the complex friction interface dynamics remain a challenging task for measurements and modeling. Today, mostly simple and regular friction models are investigated in the field of self-excited brake system vibrations. This work aims at investigating the effect of high-frequency irregular interface dynamics on the nonlinear dynamical response of a self-excited structure. Special focus is put on the characterization of the system response time series. A low-dimensional minimal model is studied which features self-excitation, gyroscopic effects and friction-induced damping. Additionally, the employed friction formulation exhibits temperature as inner variable and superposed chaotic fluctuations governed by a Lorenz attractor. The time scale of the irregular fluctuations is chosen one order smaller than the overall system dynamics. The influence of those fluctuations on the structural response is studied in various ways, i.e. in time domain and by means of recurrence analysis. The separate time scales are studied in detail and regimes of dynamic interactions are identified. The results of the irregular friction formulation indicate dynamic interactions on multiple time scales, which trigger larger vibration amplitudes as compared to regular friction formulations conventionally studied in the field of friction-induced vibrations.

The impact of volcanic aerosol on the Northern Hemisphere stratospheric polar vortex: mechanisms and sensitivity to forcing structure

NASA Astrophysics Data System (ADS)

Toohey, M.; Krüger, K.; Bittner, M.; Timmreck, C.; Schmidt, H.

2014-12-01

Observations and simple theoretical arguments suggest that the Northern Hemisphere (NH) stratospheric polar vortex is stronger in winters following major volcanic eruptions. However, recent studies show that climate models forced by prescribed volcanic aerosol fields fail to reproduce this effect. We investigate the impact of volcanic aerosol forcing on stratospheric dynamics, including the strength of the NH polar vortex, in ensemble simulations with the Max Planck Institute Earth System Model. The model is forced by four different prescribed forcing sets representing the radiative properties of stratospheric aerosol following the 1991 eruption of Mt. Pinatubo: two forcing sets are based on observations, and are commonly used in climate model simulations, and two forcing sets are constructed based on coupled aerosol-climate model simulations. For all forcings, we find that simulated temperature and zonal wind anomalies in the NH high latitudes are not directly impacted by anomalous volcanic aerosol heating. Instead, high-latitude effects result from enhancements in stratospheric residual circulation, which in turn result, at least in part, from enhanced stratospheric wave activity. High-latitude effects are therefore much less robust than would be expected if they were the direct result of aerosol heating. Both observation-based forcing sets result in insignificant changes in vortex strength. For the model-based forcing sets, the vortex response is found to be sensitive to the structure of the forcing, with one forcing set leading to significant strengthening of the polar vortex in rough agreement with observation-based expectations. Differences in the dynamical response to the forcing sets imply that reproducing the polar vortex responses to past eruptions, or predicting the response to future eruptions, depends on accurate representation of the space-time structure of the volcanic aerosol forcing.

Probing the structure of Leishmania major DHFR TS and structure based virtual screening of peptide library for the identification of anti-leishmanial leads.

PubMed

Rajasekaran, Rajalakshmi; Chen, Yi-Ping Phoebe

2012-09-01

Leishmaniasis, a multi-faceted ethereal disease is considered to be one of the World's major communicable diseases that demands exhaustive research and control measures. The substantial data on these protozoan parasites has not been utilized completely to develop potential therapeutic strategies against Leishmaniasis. Dihydrofolate reductase thymidylate synthase (DHFR-TS) plays a major role in the infective state of the parasite and hence the DHFR-TS based drugs remains of much interest to researchers working on Leishmaniasis. Although, crystal structures of DHFR-TS from different species including Plasmodium falciparum and Trypanosoma cruzi are available, the experimentally determined structure of the Leishmania major DHFR-TS has not yet been reported in the Protein Data Bank. A high quality three dimensional structure of L.major DHFR-TS has been modeled through the homology modeling approach. Carefully refined and the energy minimized structure of the modeled protein was validated using a number of structure validation programs to confirm its structure quality. The modeled protein structure was used in the process of structure based virtual screening to figure out a potential lead structure against DHFR TS. The lead molecule identified has a binding affinity of 0.51 nM and clearly follows drug like properties.

Attitudes to research and research training among ophthalmologists and ophthalmology trainees in New Zealand.

PubMed

Jayasundera, Thiran; Fisk, Michael; McGhee, Charles N J

2003-08-01

To determine the attitudes to research and research training among ophthalmologists and ophthalmology trainees in New Zealand. A structured, self-administered questionnaire was devised and after preliminary validation a postal survey was sent to all ophthalmologists and ophthalmology registrars and fellows in New Zealand. A total of 82 replies were received from 115 questionnaires sent out; a response rate of 71.3%. An overwhelming majority found research to have benefited their education, clinical practice and career; 67.1% of the respondents intended to do research in the future. Although a majority (56.4%) felt research to be beneficial to ophthalmology training, 42.3% felt research would be of limited or no benefit when selecting candidates for vocational training. However, 97.5% of respondents felt that ophthalmology trainees should undertake some form of research during training, with most supporting small studies or case reports (44.4%) or a short structured training course in research (42.0%). Interestingly, 86.6% felt that research methodology and data analysis should be taught in a structured fashion with most supporting courses or seminars of a few weeks duration during the vocational training period. Many ophthalmologists felt inadequately equipped or trained to mentor and supervise trainees undertaking research and 41.5% of consultant ophthalmologists felt further training to fulfil this role would be beneficial. This survey suggests that New Zealand ophthalmologists generally approve of and support a place for research, possibly of a more structured design, during ophthalmology training.

The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data reveals a conserved fold of the m02-m06 viral immune modulator family.

PubMed

Sgourakis, Nikolaos G; Natarajan, Kannan; Ying, Jinfa; Vogeli, Beat; Boyd, Lisa F; Margulies, David H; Bax, Ad

2014-09-02

Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a β fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of remote sensing data to structural analysis of the East Kalimantan, Indonesia

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

Moriya, Shunji; Nishidai, Takashi

1996-07-01

JERS-1 SAR and LANDSAT TM images of the northern Kutei Basin, East Kalimantan, Indonesia were geologically interpreted. The focus of the study is on the structural analysis of the Samarinda Anticlinorium located in the onshore area of the Kutei Basin. In the Samarinda Anticlinorium, N-S folds and thrusts are well developed in the Tertiary sediments. They are believed to have been formed during the Middle Miocene or later. In addition to the N-S structure, an extensive NW-SE lineament traversing the central part of the study area can be identified on the images. Image interpretation reveals that this lineament is amore » major fault formed before the Oligocene. Noticeable differences in the N-S structure are recognized at the north and south of this NW-SE fault, Lithology and thickness of the sediments overlying the basement are remarkably different at the north and south of the fault. These may be responsible for the differences in the N-S structure of the northern and southern Anticlinorium.« less

Insights into soybean transcriptome reconfiguration under hypoxic stress: Functional, regulatory, structural, and compositional characterization.

PubMed

Nakayama, Thiago J; Rodrigues, Fabiana A; Neumaier, Norman; Marcolino-Gomes, Juliana; Molinari, Hugo B C; Santiago, Thaís R; Formighieri, Eduardo F; Basso, Marcos F; Farias, José R B; Emygdio, Beatriz M; de Oliveira, Ana C B; Campos, Ângela D; Borém, Aluízio; Harmon, Frank G; Mertz-Henning, Liliane M; Nepomuceno, Alexandre L

2017-01-01

Soybean (Glycine max) is one of the major crops worldwide and flooding stress affects the production and expansion of cultivated areas. Oxygen is essential for mitochondrial aerobic respiration to supply the energy demand of plant cells. Because oxygen diffusion in water is 10,000 times lower than in air, partial (hypoxic) or total (anoxic) oxygen deficiency is important component of flooding. Even when oxygen is externally available, oxygen deficiency frequently occurs in bulky, dense or metabolically active tissues such as phloem, meristems, seeds, and fruits. In this study, we analyzed conserved and divergent root transcriptional responses between flood-tolerant Embrapa 45 and flood-sensitive BR 4 soybean cultivars under hypoxic stress conditions with RNA-seq. To understand how soybean genes evolve and respond to hypoxia, stable and differentially expressed genes were characterized structurally and compositionally comparing its mechanistic relationship. Between cultivars, Embrapa 45 showed less up- and more down-regulated genes, and stronger induction of phosphoglucomutase (Glyma05g34790), unknown protein related to N-terminal protein myristoylation (Glyma06g03430), protein suppressor of phyA-105 (Glyma06g37080), and fibrillin (Glyma10g32620). RNA-seq and qRT-PCR analysis of non-symbiotic hemoglobin (Glyma11g12980) indicated divergence in gene structure between cultivars. Transcriptional changes for genes in amino acids and derivative metabolic process suggest involvement of amino acids metabolism in tRNA modifications, translation accuracy/efficiency, and endoplasmic reticulum stress in both cultivars under hypoxia. Gene groups differed in promoter TATA box, ABREs (ABA-responsive elements), and CRT/DREs (C-repeat/dehydration-responsive elements) frequency. Gene groups also differed in structure, composition, and codon usage, indicating biological significances. Additional data suggests that cis-acting ABRE elements can mediate gene expression independent of ABA in soybean roots under hypoxia.

Role of extensional structures on the location of folds and thrusts during tectonic inversion (northern Iberian Chain, Spain)

NASA Astrophysics Data System (ADS)

Cortés, Angel L.; Liesa, Carlos L.; Soria, Ana R.; Meléndez, Alfonso

1999-03-01

The Aguilón Subbasin (NE Spain) was originated daring the Late Jurassic-Early Cretaceous rifting due to the action of large normal faults, probably inherited from Late Variscan fracturing. WNW-ESE normal faults limit two major troughs filled by continental deposits (Valanginian to Early Barremian). NE-SW faults control the location of subsidiary depocenters within these troughs. These basins were weakly inverted during the Tertiary with folds and thrusts striking E-W to WNW-ESE involving the Mesozoic-Tertiary cover with a maximum estimated shortening of about 12 %. Tertiary compression did not produce the total inversion of the Mesozoic basin but extensional structures are responsible for the location of major Tertiary folds. Shortening of the cover during the Tertiary involved both reactivation of some normal faults and development of folds and thrusts nucleated on basement extensional steps. The inversion style depends mainly on the occurrence and geometry of normal faults limiting the basin. Steep normal faults were not reactivated but acted as buttresses to the cover translation. Around these faults, affecting both basement and cover, folds and thrusts were nucleated due to the stress rise in front of major faults. Within the cover, the buttressing against normal faults consists of folding and faulting implying little shortening without development of ceavage or other evidence of internal deformation.

Contrasting soil microbial community functional structures in two major landscapes of the Tibetan alpine meadow

DOE PAGES

Chu, Houjuan; Wang, Shiping; Yue, Haowei; ...

2014-07-07

The grassland and shrubland are two major landscapes of the Tibetan alpine meadow, a region very sensitive to the impact of global warming and anthropogenic perturbation. Herein, we report a study showing that a majority of differences in soil microbial community functional structures, measured by a functional gene array named GeoChip 4.0, in two adjacent shrubland and grassland areas, were explainable by environmental properties, suggesting that the harsh environments in the alpine grassland rendered niche adaptation important. Furthermore, genes involved in labile carbon degradation were more abundant in the shrubland than those of the grassland but genes involved in recalcitrantmore » carbon degradation were less abundant, which was conducive to long-term carbon storage and sequestration in the shrubland despite low soil organic carbon content. In addition, genes of anerobic nitrogen cycling processes such as denitrification and dissimilatory nitrogen reduction were more abundant, shifting soil nitrogen cycling toward ammonium biosynthesis and consequently leading to higher soil ammonium contents. In conclusion, we also noted higher abundances of stress genes responsive to nitrogen limitation and oxygen limitation, which might be attributed to low total nitrogen and higher water contents in the shrubland. Together, these results provide mechanistic knowledge about microbial linkages to soil carbon and nitrogen storage and potential consequences of vegetation shifts in the Tibetan alpine meadow.« less

Sinking coastal cities

NASA Astrophysics Data System (ADS)

Erkens, G.; Bucx, T.; Dam, R.; de Lange, G.; Lambert, J.

2015-11-01

In many coastal and delta cities land subsidence now exceeds absolute sea level rise up to a factor of ten. A major cause for severe land subsidence is excessive groundwater extraction related to rapid urbanization and population growth. Without action, parts of Jakarta, Ho Chi Minh City, Bangkok and numerous other coastal cities will sink below sea level. Land subsidence increases flood vulnerability (frequency, inundation depth and duration of floods), with floods causing major economic damage and loss of lives. In addition, differential land movement causes significant economic losses in the form of structural damage and high maintenance costs for (infra)structure. The total damage worldwide is estimated at billions of dollars annually. As subsidence is often spatially variable and can be caused by multiple processes, an assessment of subsidence in delta cities needs to answer questions such as: what are the main causes? What is the current subsidence rate and what are future scenarios (and interaction with other major environmental issues)? Where are the vulnerable areas? What are the impacts and risks? How can adverse impacts be mitigated or compensated for? Who is involved and responsible to act? In this study a quick-assessment of subsidence is performed on the following mega-cities: Jakarta, Ho Chi Minh City, Dhaka, New Orleans and Bangkok. Results of these case studies will be presented and compared, and a (generic) approach how to deal with subsidence in current and future subsidence-prone areas is provided.

Integrating in silico prediction methods, molecular docking, and molecular dynamics simulation to predict the impact of ALK missense mutations in structural perspective.

PubMed

Doss, C George Priya; Chakraborty, Chiranjib; Chen, Luonan; Zhu, Hailong

2014-01-01

Over the past decade, advancements in next generation sequencing technology have placed personalized genomic medicine upon horizon. Understanding the likelihood of disease causing mutations in complex diseases as pathogenic or neutral remains as a major task and even impossible in the structural context because of its time consuming and expensive experiments. Among the various diseases causing mutations, single nucleotide polymorphisms (SNPs) play a vital role in defining individual's susceptibility to disease and drug response. Understanding the genotype-phenotype relationship through SNPs is the first and most important step in drug research and development. Detailed understanding of the effect of SNPs on patient drug response is a key factor in the establishment of personalized medicine. In this paper, we represent a computational pipeline in anaplastic lymphoma kinase (ALK) for SNP-centred study by the application of in silico prediction methods, molecular docking, and molecular dynamics simulation approaches. Combination of computational methods provides a way in understanding the impact of deleterious mutations in altering the protein drug targets and eventually leading to variable patient's drug response. We hope this rapid and cost effective pipeline will also serve as a bridge to connect the clinicians and in silico resources in tailoring treatments to the patients' specific genotype.

Bridging cultures: Nonprofit, church, and emergency management agency collaboration after the May 2013 Oklahoma tornado outbreak.

PubMed

Murphy, Haley; Pudlo, Jason

Community-based organizations, such as nonprofit organizations (NPOs) and churches, play an important role in helping individuals and communities bounce back after a disaster. The nature of disasters requires organizations across sectors to partner together to provide recovery services; however, collaboration is difficult even in times of stability and requires trust and communication to be built through prior collaborative relationships. These prior relationships rarely exist between the majority of the nonprofit sector, churches, and existing emergency management structures. Furthermore, these organizations often have very different cultures, values, and norms that can further hinder successful postdisaster collaboration. The authors use data collected from interviews with nonprofit and church leaders involved in recovery efforts after a series of devastating storms impacted central Oklahoma in 2013 to understand how well nonprofit and church leaders perceive their organizations collaborated with each other and with government and emergency management agencies in response and recovery efforts. Interview data suggest that NPOs and churches without a primary or secondary mission of disaster response and recovery have a difficult time collaborating with organizations involved in existing emergency management structures. The authors suggest that nonprofits with a primary or secondary purpose in disaster response are a potential bridge between other nonprofits and emergency management agencies.

Neuronal plasticity and seasonal reproduction in sheep

PubMed Central

Lehman, Michael N.; Ladha, Zamin; Coolen, Lique M.; Hileman, Stanley M.; Connors, John M.; Goodman, Robert L.

2010-01-01

Seasonal reproduction represents a naturally occurring example of functional plasticity in the adult brain since it reflects changes in neuroendocrine pathways controlling GnRH secretion and, in particular, the responsiveness of GnRH neurons to estradiol negative feedback. Structural plasticity within this neural circuitry may, in part, be responsible for seasonal switches in the negative feedback control of GnRH secretion that underlies annual reproductive transitions. In this paper, we review evidence for structural changes in the circuitry responsible for seasonal inhibition of GnRH secretion in sheep. These include changes in synaptic inputs onto GnRH neurons, as well as onto dopamine neurons in the A15 cell group, a nucleus that play a key role in estradiol negative feedback. We also present preliminary data suggesting a role for neurotrophins and neurotrophin receptors as an early mechanistic step in the plasticity that accompanies seasonal reproductive transitions in the sheep. Finally, we review recent evidence suggesting that kisspeptin cells of the arcuate nucleus constitute a critical intermediary in the control of seasonal reproduction. While a majority of the data for a role of neuronal plasticity in seasonal reproduction has come from the sheep model, the players and principles are likely to have relevance for reproduction in a wide variety of vertebrates, including humans, and in both health and disease. PMID:21143669

Review. Neurobiological mechanisms for opponent motivational processes in addiction.

PubMed

Koob, George F; Le Moal, Michel

2008-10-12

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

Earthquake casualty models within the USGS Prompt Assessment of Global Earthquakes for Response (PAGER) system

USGS Publications Warehouse

Jaiswal, Kishor; Wald, David J.; Earle, Paul S.; Porter, Keith A.; Hearne, Mike

2011-01-01

Since the launch of the USGS’s Prompt Assessment of Global Earthquakes for Response (PAGER) system in fall of 2007, the time needed for the U.S. Geological Survey (USGS) to determine and comprehend the scope of any major earthquake disaster anywhere in the world has been dramatically reduced to less than 30 min. PAGER alerts consist of estimated shaking hazard from the ShakeMap system, estimates of population exposure at various shaking intensities, and a list of the most severely shaken cities in the epicentral area. These estimates help government, scientific, and relief agencies to guide their responses in the immediate aftermath of a significant earthquake. To account for wide variability and uncertainty associated with inventory, structural vulnerability and casualty data, PAGER employs three different global earthquake fatality/loss computation models. This article describes the development of the models and demonstrates the loss estimation capability for earthquakes that have occurred since 2007. The empirical model relies on country-specific earthquake loss data from past earthquakes and makes use of calibrated casualty rates for future prediction. The semi-empirical and analytical models are engineering-based and rely on complex datasets including building inventories, time-dependent population distributions within different occupancies, the vulnerability of regional building stocks, and casualty rates given structural collapse.

ALCOHOL AND THE PREFRONTAL CORTEX

PubMed Central

Abernathy, Kenneth; Chandler, L. Judson; Woodward, John J.

2013-01-01

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. PMID:20813246

Evolution of the Genetic and Neural Architecture for Vertebrate Odor Perception

PubMed Central

Bear, Daniel M.; Lassance, Jean-Marc; Hoekstra, Hopi E.; Datta, Sandeep Robert

2016-01-01

Evolution sculpts the olfactory nervous system in response to the unique sensory challenges facing each species. In vertebrates, dramatic and diverse adaptations to the chemical environment are possible because of the hierarchical structure of the olfactory receptor (OR) gene superfamily: rapid growth or pruning across the OR gene tree accompany major changes in habitat and lifestyle; independent selection on OR subfamilies can permit local adaptation or conserved chemical communication; and genetic variation in single OR genes among thousands can alter odor percepts and behaviors driven by precise chemical cues. However, this genetic flexibility contrasts with the relatively fixed neural architecture of the vertebrate olfactory system, whose slower rate of divergence mandates that new olfactory receptors integrate into segregated and functionally-distinct neural pathways. This organization allows evolution to couple critical chemical signals with selectively advantageous responses, but also constrains relationships between olfactory receptors and behavior. The coevolution of the OR repertoire and the structure of the olfactory system therefore reveals general principles of how the brain solves specific sensory problems and how it adapts to new ones. PMID:27780046

Correlating Fluorescence and High-Resolution Scanning Electron Microscopy (HRSEM) for the study of GABAA receptor clustering induced by inhibitory synaptic plasticity.

PubMed

Orlando, Marta; Ravasenga, Tiziana; Petrini, Enrica Maria; Falqui, Andrea; Marotta, Roberto; Barberis, Andrea

2017-10-23

Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed synaptic plasticity. Although the molecular mechanisms underlying glutamatergic synaptic plasticity have been extensively investigated and described, those responsible for inhibitory synaptic plasticity are only beginning to be unveiled. In this framework, the ultrastructural changes of the inhibitory synapses during plasticity have been poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to characterize the fine structural rearrangements of post-synaptic GABA A Receptors (GABA A Rs) at the nanometric scale during the induction of inhibitory long-term potentiation (iLTP). Additional electron tomography (ET) experiments on immunolabelled hippocampal neurons allowed the visualization of synaptic contacts and confirmed the reorganization of post-synaptic GABA A R clusters in response to chemical iLTP inducing protocol. Altogether, these approaches revealed that, following the induction of inhibitory synaptic potentiation, GABA A R clusters increase in size and number at the post-synaptic membrane with no other major structural changes of the pre- and post-synaptic elements.

Phosphoglycerolipids are master players in plant hormone signal transduction.

PubMed

Janda, Martin; Planchais, Severine; Djafi, Nabila; Martinec, Jan; Burketova, Lenka; Valentova, Olga; Zachowski, Alain; Ruelland, Eric

2013-06-01

Phosphoglycerolipids are essential structural constituents of membranes and some also have important cell signalling roles. In this review, we focus on phosphoglycerolipids that are mediators in hormone signal transduction in plants. We first describe the structures of the main signalling phosphoglycerolipids and the metabolic pathways that generate them, namely the phospholipase and lipid kinase pathways. In silico analysis of Arabidopsis transcriptome data provides evidence that the genes encoding the enzymes of these pathways are transcriptionally regulated in responses to hormones, suggesting some link with hormone signal transduction. The involvement of phosphoglycerolipid signalling in the early responses to abscisic acid, salicylic acid and auxins is then detailed. One of the most important signalling lipids in plants is phosphatidic acid. It can activate or inactivate protein kinases and/or protein phosphatases involved in hormone signalling. It can also activate NADPH oxidase leading to the production of reactive oxygen species. We will interrogate the mechanisms that allow the activation/deactivation of the lipid pathways, in particular the roles of G proteins and calcium. Mediating lipids thus appear as master players of cell signalling, modulating, if not controlling, major transducing steps of hormone signals.

The behavior of Aluminium Carbon/Epoxy fibre metal laminate under quasi-static loading

NASA Astrophysics Data System (ADS)

Romli, N. K.; Rejab, M. R. M.; Bachtiar, D.; Siregar, J.; Rani, M. F.; Harun, W. S. W.; Salleh, Salwani Mohd; Merzuki, M. N. M.

2017-10-01

One of major concerns that related to the flight safety is impact of birds. To minimize the risks, there is need to increase the impact resistance of aircraft by developing a new material and has the good structural design of aircraft structures. The hybrid laminates are potential candidate material to be applied for the aircraft structures susceptible to bird strikes. The fibre metal laminate was fabricated by a compression moulding technique. The carbon fibre and aluminium alloy 2024-0 was laminated by using thermoset epoxy. A compression moulding technique was used for the FML fabrication. The aluminium sheet metal has been roughening by a metal sanding method which to improve the bonding between the fibre and metal layer. The main objective of this paper is to determine the failure response of the laminate under five variations of the crosshead displacement in the quasi-static loading. The FML was modelled and analysed by using Explicit solver. Based on the experimental data of the quasi-static test, the result of 1 mm/min was 11.85 kN and higher than 5, 10, 50 and 100 mm/min which because of the aluminium ductility during the impact loading response. The numerical simulations were generally in good agreement with the experimental measurements.

Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

PubMed

Liu, Peng; Fan, Liyun; Hayat, Qaisar; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined.

Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

PubMed Central

Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

Consistent responses of the microbial community structure to organic farming along the middle and lower reaches of the Yangtze River

PubMed Central

Wang, Wenhui; Wang, Hui; Feng, Youzhi; Wang, Lei; Xiao, Xingji; Xi, Yunguan; Luo, Xue; Sun, Ruibo; Ye, Xianfeng; Huang, Yan; Zhang, Zhengguang; Cui, Zhongli

2016-01-01

Soil microorganisms play a crucial role in the biogeochemical cycling of nutrient elements and maintaining soil health. We aimed to investigate the response of bacteria communities to organic farming over different crops (rice, tea and vegetable) along the middle and lower reaches of the Yangtze River of China. Compared with conventional farming, organic farming significantly increased soil nutrients, soil enzyme activities, and bacterial richness and diversity. A Venn diagram and principal component analysis revealed that the soils with 3 different crops under organic farming have more number and percent of shared OTUs (operational taxonomic units), and shared a highly similar microbial community structure. Under organic farming, several predominant guilds and major bacterial lineages (Rhizobiales, Thiotrichaceae, Micromonosporaceae, Desulfurellaceae and Myxococcales) contributing to nutrient (C, N, S and P) cycling were enriched, whereas the relative abundances of acid and alkali resistant microorganisms (Acidobacteriaceae and Sporolactobacillaceae) were increased under conventional farming practices. Our results indicated that, for all three crops, organic farming have a more stable microflora and the uniformity of the bacterial community structure. Organic agriculture significantly increased the abundance of some nutrition-related bacteria, while reducing some of the abundance of acid and alkali resistant bacteria. PMID:27725750

A worldwide analysis of within-canopy variations in leaf structural, chemical and physiological traits across plant functional types

PubMed Central

Niinemets, Ülo; Keenan, Trevor F.; Hallik, Lea

2018-01-01

Summary Extensive within-canopy light gradients importantly affect photosynthetic productivity of leaves in different canopy positions and lead to light-dependent increases in foliage photosynthetic capacity per area (AA). However, the controls on AA variations by changes in underlying traits are poorly known. We constructed an unprecedented worldwide database including 831 within-canopy gradients with standardized light estimates for 304 species belonging to major vascular plant functional types, and analyzed within-canopy variations in 12 key foliage structural, chemical and physiological traits by quantitatively separating the contributions of different traits to photosynthetic acclimation. Although the light-dependent increase in AA is surprisingly similar in different plant functional types, they fundamentally differ in the share of the controls on AA by constituent traits. Species with high rates of canopy development and leaf turnover exhibiting highly dynamic light environments, actively change AA by nitrogen reallocation among and partitioning within leaves. In contrast, species with slow leaf turnover exhibit a passive AA acclimation response primarily determined by acclimation of leaf structure to growth light. This review emphasizes that different combinations of traits are responsible for within-canopy photosynthetic acclimation in different plant functional types and solves an old enigma of the role of mass- vs. area-based traits in vegetation acclimation. PMID:25318596

[Research advances of fluid bio-mechanics in bone].

PubMed

Chen, Zebin; Huo, Bo

2017-04-01

It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

Active control of aerothermoelastic effects for a conceptual hypersonic aircraft

NASA Technical Reports Server (NTRS)

Heeg, Jennifer; Gilbert, Michael G.; Pototzky, Anthony S.

1990-01-01

This paper describes the procedures for an results of aeroservothermoelastic studies. The objectives of these studies were to develop the necessary procedures for performing an aeroelastic analysis of an aerodynamically heated vehicle and to analyze a configuration in the classical 'cold' state and in a 'hot' state. Major tasks include the development of the structural and aerodynamic models, open loop analyses, design of active control laws for improving dynamic responses and analyses of the closed loop vehicles. The analyses performed focused on flutter speed calculations, short period eigenvalue trends and statistical analyses of the vehicle response to controls and turbulence. Improving the ride quality of the vehicle and raising the flutter boundary of the aerodynamically-heated vehicle up to that of the cold vehicle were the objectives of the control law design investigations.

Hydrazone linkages in pH responsive drug delivery systems.

PubMed

Sonawane, Sandeep J; Kalhapure, Rahul S; Govender, Thirumala

2017-03-01

Stimuli-responsive polymeric drug delivery systems using various triggers to release the drug at the sites have become a major focus area. Among various stimuli-responsive materials, pH-responsiveness has been studied extensively. The materials used for fabricating pH-responsive drug delivery systems include a specific chemical functionality in their structure that can respond to changes in the pH of the surrounding environment. Various chemical functionalities, for example, acetal, amine, ortho ester, amine and hydrazone, have been used to design materials that are capable of releasing their payload at the acidic pH conditions of the tumor or infection sites. Hydrazone linkages are significant synthons for numerous transformations and have gained importance in pharmaceutical sciences due to their various biological and clinical applications. These linkages have been employed in various drug delivery vehicles, such as linear polymers, star shaped polymers, dendrimers, micelles, liposomes and inorganic nanoparticles, for pH-responsive drug delivery. This review paper focuses on the synthesis and characterization methods of hydrazone bond containing materials and their applications in pH-responsive drug delivery systems. It provides detailed suggestions as guidelines to materials and formulation scientists for designing biocompatible pH-responsive materials with hydrazone linkages and identifying future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Reflections on Communicating Science during the Canterbury Earthquake Sequence of 2010-2011, New Zealand

NASA Astrophysics Data System (ADS)

Wein, A. M.; Berryman, K. R.; Jolly, G. E.; Brackley, H. L.; Gledhill, K. R.

2015-12-01

The 2010-2011 Canterbury Earthquake Sequence began with the 4th September 2010 Darfield earthquake (Mw 7.1). Perhaps because there were no deaths, the mood of the city and the government was that high standards of earthquake engineering in New Zealand protected us, and there was a confident attitude to response and recovery. The demand for science and engineering information was of interest but not seen as crucial to policy, business or the public. The 22nd February 2011 Christchurch earthquake (Mw 6.2) changed all that; there was a significant death toll and many injuries. There was widespread collapse of older unreinforced and two relatively modern multi-storey buildings, and major disruption to infrastructure. The contrast in the interest and relevance of the science could not have been greater compared to 5 months previously. Magnitude 5+ aftershocks over a 20 month period resulted in confusion, stress, an inability to define a recovery trajectory, major concerns about whether insurers and reinsurers would continue to provide cover, very high levels of media interest from New Zealand and around the world, and high levels of political risk. As the aftershocks continued there was widespread speculation as to what the future held. During the sequence, the science and engineering sector sought to coordinate and offer timely and integrated advice. However, other than GeoNet, the national geophysical monitoring network, there were few resources devoted to communication, with the result that it was almost always reactive. With hindsight we have identified the need to resource information gathering and synthesis, execute strategic assessments of stakeholder needs, undertake proactive communication, and develop specific information packages for the diversity of users. Overall this means substantially increased resources. Planning is now underway for the science sector to adopt the New Zealand standardised CIMS (Coordinated Incident Management System) structure for management and communication during a crisis, which should help structure and resource the science response needs in future major events.

Comparison of vibrations of a combination of solid-rocket launch vehicle and payload during a ground firing and launching

NASA Technical Reports Server (NTRS)

Schoenster, J. A.; Pierce, H. B.

1975-01-01

The results of a study into the environmental vibrations of a payload mounted on the Nike rocket launch vehicle were presented. Data were obtained during the flight acceptance test of the payload, the firing of the total vehicle in a special test stand, and the powered and unpowered flights of the vehicle. The vibrational response of the structure was measured. Data were also obtained on the fluctuating pressure on the outside surface of the vehicle and inside the forward and after ends of the rocket chamber. A comparison of the data from the three test conditions indicated that external pressure fluctuations were the major source of vibrations in the payload area, and pressure fluctuations within the rocket motor were the major source of vibrations contiguous to the payload area.

The FlyBase database of the Drosophila genome projects and community literature

PubMed Central

2002-01-01

FlyBase (http://flybase.bio.indiana.edu/) provides an integrated view of the fundamental genomic and genetic data on the major genetic model Drosophila melanogaster and related species. Following on the success of the Drosophila genome project, FlyBase has primary responsibility for the continual reannotation of the D.melanogaster genome. The ultimate goal of the reannotation effort is to decorate the euchromatic sequence of the genome with as much biological information as is available from the community and from the major genome project centers. The current cycle of reannotation focuses on establishing a comprehensive data set of gene models (i.e. transcription units and CDSs). There are many points of entry to the genome within FlyBase, most notably through maps, gene ontologies, structured phenotypic and gene expression data, and anatomy. PMID:11752267

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

Venkatraman, Srikanth; Bogen, Stephane L.; Arasappan, Ashok

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-{alpha} or polyethylene glycol (PEG)-interferon-{alpha} alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitormore » that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.« less

The personal and general hygiene practices of food handlers in the delicatessen sections of retail outlets in South Africa.

PubMed

van Tonder, Izanne; Lues, Jan F R; Theron, Maria M

2007-11-01

This paper presents data on personal- and general-hygiene knowledge and practices among food handlers in the delicatessens of a major retail group in the Western Cape in South Africa. Food handlers were interviewed by means of a structured questionnaire. Although the majority of food handlers adhered to basic hygiene principles, there is definitely a need for proper and continuous training in personal and general hygiene, not only for food handlers, but also for management. The study reported here is of importance particularly in view of new local regulations governing the application of the hazard analysis and critical control point (HACCP) system. Management is responsible for the implementation of this system, and where supervision is not adequate, the manager of the outlet should intervene to ensure that staff conform to the requirements.

Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients

PubMed Central

Aw-Yong, Kam Leng; Sam, I-Ching; Koh, Mia Tuang

2016-01-01

Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142–156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41–55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates. PMID:27806091

Exploratory analysis of real personal emergency response call conversations: considerations for personal emergency response spoken dialogue systems.

PubMed

Young, Victoria; Rochon, Elizabeth; Mihailidis, Alex

2016-11-14

The purpose of this study was to derive data from real, recorded, personal emergency response call conversations to help improve the artificial intelligence and decision making capability of a spoken dialogue system in a smart personal emergency response system. The main study objectives were to: develop a model of personal emergency response; determine categories for the model's features; identify and calculate measures from call conversations (verbal ability, conversational structure, timing); and examine conversational patterns and relationships between measures and model features applicable for improving the system's ability to automatically identify call model categories and predict a target response. This study was exploratory and used mixed methods. Personal emergency response calls were pre-classified according to call model categories identified qualitatively from response call transcripts. The relationships between six verbal ability measures, three conversational structure measures, two timing measures and three independent factors: caller type, risk level, and speaker type, were examined statistically. Emergency medical response services were the preferred response for the majority of medium and high risk calls for both caller types. Older adult callers mainly requested non-emergency medical service responders during medium risk situations. By measuring the number of spoken words-per-minute and turn-length-in-words for the first spoken utterance of a call, older adult and care provider callers could be identified with moderate accuracy. Average call taker response time was calculated using the number-of-speaker-turns and time-in-seconds measures. Care providers and older adults used different conversational strategies when responding to call takers. The words 'ambulance' and 'paramedic' may hold different latent connotations for different callers. The data derived from the real personal emergency response recordings may help a spoken dialogue system classify incoming calls by caller type with moderate probability shortly after the initial caller utterance. Knowing the caller type, the target response for the call may be predicted with some degree of probability and the output dialogue could be tailored to this caller type. The average call taker response time measured from real calls may be used to limit the conversation length in a spoken dialogue system before defaulting to a live call taker.

Evidence of major genes for plasma HDL, LDL cholesterol and triglyceride levels at baseline and in response to 20 weeks of endurance training: the HERITAGE Family Study.

PubMed

An, P; Borecki, I B; Rankinen, T; Després, J-P; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2005-01-01

This study assessed major gene effects for baseline HDL-C, LDL-C, TG, and their training responses (post-training minus baseline) in 527 individuals from 99 White families and 326 individuals from 113 Black families in the HERITAGE Family Study. The baseline phenotypes were adjusted for the effects of age and BMI, and the training response phenotypes were adjusted for the effects of age, BMI, and their respective baseline values, within each of the sex-by-generation-by-race groups, prior to genetic analyses. In Whites, we found that LDL-C at baseline and HDL-C training response were under influence of major recessive genes (accounting for 2--30 % of the variance) and multifactorial (polygenic and familial environmental) effects. Interactions of these major genes with sex, age, and BMI were tested, and found to be nonsignificant. In Blacks, we found that baseline HDL-C was influenced by a major dominant gene without a multifactorial component. This major gene effect accounted for 45 % of the variance, and exhibited no significant genotype-specific interactions with age, sex, and BMI. Evidence of major genes for the remaining phenotypes at baseline and in response to endurance training were not found in both races, though some were influenced by major effects that did not follow Mendelian expectations or were with ambiguous transmission from parents to offspring. In summary, major gene effects that influence baseline plasma HDL-C and LDL-C levels as well as changes in HDL-C levels in response to regular exercise were detected in the current study.

Modélisation magnétotellurique de la structure géologique profonde de l’unité granulitique de l’In Ouzzal (Hoggar occidental)

NASA Astrophysics Data System (ADS)

Bouzid, Abderrezak; Akacem, Nouredine; Hamoudi, Mohamed; Ouzegane, Khadidja; Abtout, Abdeslam; Kienast, Jean-Robert

2008-11-01

Magnetotelluric modeling of the deep geologic structure of In Ouzzal Granulitic Unit (western Hoggar). The In Ouzzal Granulitic Unit (IOGU) or In Ouzzal Terrane (IOT) is an Archaean block belonging to the Hoggar terrane mosaic. It has been reworked during the Eburnean and is characterized by ultrahigh temperature metamorphism of the structures, which are likely to be old dome and basin structures. The aim of this study, based on a survey of 12 magnetotelluric (MT) soundings, was to characterize the IOGU deep lateral boundaries and to see if it is possible to reconstruct some of these old dome and basin structures after their transformation by metamorphism and deformation. MT data analysis and modeling show that IOGU boundaries extend downwards, at least down to the crust's basement, and may represent suture zones. Inside the terrane, the MT observations do not allow separation between dome and basin structures, because these features are severely stretched. However, the main MT transverse response feature is a deeply rooted great accident, which may be interpreted as a major fault that separates IOGU into two compartments.

FT-IR Study Reveals Intrinsically Disordered Nature of Heat Shock Protein 90

NASA Astrophysics Data System (ADS)

Xie, Aihua; Neto, David; Balch, Maurie; Hendriks, Johnny; Causey, Oliver; Deng, Junpeng; Matts, Robert

Heat shock protein 90 (Hsp90) is a highly conserved chaperone protein that enables the proper folding of a large number of structurally diverse proteins (a.k.a., clients) in the crowded cytosolic environment and plays a key role in regulating the heat shock response. A long standing open question is how Hsp90 accommodates the structural diversity of a large cohort of client proteins? We report ATR FTIR study on structural properties of Hsp90 C-terminal domain (CTD) and their temperature dependences. Effects of temperature on Hsp90 structure are dissected into the C-terminal domain (CTD) and the N-terminal/middle domain (NTMD). One of our major findings reveals that within a narrow temperature window across the physiological temperatures (35 to 45 C), Hsp90CTD exhibits significant increases in protein aggregation and increases in unordered structures. Despite the intrinsically disordered nature of Hsp90CTD, it retains a protected hydrophobic core at 40 C. Implications of these results will be discussed in the light of the structural dynamics and client diversity of Hsp90. AX is grateful for Grant supports from OCAST HR10-078 and NSF MRI DBI1338097.

Determinants of community structure of zooplankton in heavily polluted river ecosystems

NASA Astrophysics Data System (ADS)

Xiong, Wei; Li, Jie; Chen, Yiyong; Shan, Baoqing; Wang, Weimin; Zhan, Aibin

2016-02-01

River ecosystems are among the most affected habitats globally by human activities, such as the release of chemical pollutants. However, it remains largely unknown how and to what extent many communities such as zooplankton are affected by these environmental stressors in river ecosystems. Here, we aim to determine major factors responsible for shaping community structure of zooplankton in heavily polluted river ecosystems. Specially, we use rotifers in the Haihe River Basin (HRB) in North China as a case study to test the hypothesis that species sorting (i.e. species are “filtered” by environmental factors and occur at environmental suitable sites) plays a key role in determining community structure at the basin level. Based on an analysis of 94 sites across the plain region of HRB, we found evidence that both local and regional factors could affect rotifer community structure. Interestingly, further analyses indicated that local factors played a more important role in determining community structure. Thus, our results support the species sorting hypothesis in highly polluted rivers, suggesting that local environmental constraints, such as environmental pollution caused by human activities, can be stronger than dispersal limitation caused by regional factors to shape local community structure of zooplankton at the basin level.

Proteins without unique 3D structures: biotechnological applications of intrinsically unstable/disordered proteins.

PubMed

Uversky, Vladimir N

2015-03-01

Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are functional proteins or regions that do not have unique 3D structures under functional conditions. Therefore, from the viewpoint of their lack of stable 3D structure, IDPs/IDPRs are inherently unstable. As much as structure and function of normal ordered globular proteins are determined by their amino acid sequences, the lack of unique 3D structure in IDPs/IDPRs and their disorder-based functionality are also encoded in the amino acid sequences. Because of their specific sequence features and distinctive conformational behavior, these intrinsically unstable proteins or regions have several applications in biotechnology. This review introduces some of the most characteristic features of IDPs/IDPRs (such as peculiarities of amino acid sequences of these proteins and regions, their major structural features, and peculiar responses to changes in their environment) and describes how these features can be used in the biotechnology, for example for the proteome-wide analysis of the abundance of extended IDPs, for recombinant protein isolation and purification, as polypeptide nanoparticles for drug delivery, as solubilization tools, and as thermally sensitive carriers of active peptides and proteins. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distinguishing affective depersonalization from anhedonia in major depression and bipolar disorder.

PubMed

Mula, Marco; Pini, Stefano; Calugi, Simona; Preve, Matteo; Masini, Matteo; Giovannini, Ilaria; Rucci, Paola; Cassano, Giovanni B

2010-01-01

Affective depersonalization has received limited attention in the literature, although its conceptualization may have implications in terms of identification of clinical endophenotypes of mood disorders. Thus, this study aims to test the hypothesis that anhedonia and affective depersonalization represent 2 distinct psychopathological dimensions and to investigate their clinical correlates in patients with major depressive disorder (MDD) and bipolar disorder (BD). Using a data pool of 258 patients with mood and anxiety disorders, an item response theory-based factor analysis approach was carried out on 16 items derived from 2 clinical instruments developed in the Spectrum Project (the Structured Clinical Interview for Mood Spectrum and the Structured Clinical Interview for Derealization-Depersonalization Spectrum). Clinical correlates of these psychometrically derived dimensions were subsequently investigated in patients with BD or MDD. Using an item response theory-based factor analysis, a 2-factor solution was identified, accounting overall for the 47.0% of the variance. Patients with BD showed statistically significant higher affective depersonalization factor scores than those with MDD (Z = 2.215, P = .027), whereas there was no between-groups difference in anhedonia scores (Z = 0.825 P = .411). In patients with BD, age of onset of the disease correlated with affective depersonalization factor scores (rho = -0.330, P = .001) but not with anhedonia factor scores (rho = -0.097, P = .361). Affective depersonalization and anhedonia seem to be 2 distinct psychopathological dimensions, although closely related, bearing the opportunity to identify patients with a specific profile for a better clinical and neurobiological definition. Copyright 2010 Elsevier Inc. All rights reserved.

Contrasting responses to a climate regime change by sympatric, ice-dependent predators.

PubMed

Younger, Jane L; van den Hoff, John; Wienecke, Barbara; Hindell, Mark; Miller, Karen J

2016-03-15

Models that predict changes in the abundance and distribution of fauna under future climate change scenarios often assume that ecological niche and habitat availability are the major determinants of species' responses to climate change. However, individual species may have very different capacities to adapt to environmental change, as determined by intrinsic factors such as their dispersal ability, genetic diversity, generation time and rate of evolution. These intrinsic factors are usually excluded from forecasts of species' abundance and distribution changes. We aimed to determine the importance of these factors by comparing the impact of the most recent climate regime change, the late Pleistocene glacial-interglacial transition, on two sympatric, ice-dependent meso-predators, the emperor penguin (Aptenodytes forsteri) and Weddell seal (Leptonychotes weddellii). We reconstructed the population trend of emperor penguins and Weddell seals in East Antarctica over the past 75,000 years using mitochondrial DNA sequences and an extended Bayesian skyline plot method. We also assessed patterns of contemporary population structure and genetic diversity. Despite their overlapping distributions and shared dependence on sea ice, our genetic data revealed very different responses to climate warming between these species. The emperor penguin population grew rapidly following the glacial-interglacial transition, but the size of the Weddell seal population did not change. The expansion of emperor penguin numbers during the warm Holocene may have been facilitated by their higher dispersal ability and gene flow among colonies, and fine-scale differences in preferred foraging locations. The vastly different climate change responses of two sympatric ice-dependent predators suggests that differing adaptive capacities and/or fine-scale niche differences can play a major role in species' climate change responses, and that adaptive capacity should be considered alongside niche and distribution in future species forecasts.

Global Analysis of Gene Expression Profiles in Physic Nut (Jatropha curcas L.) Seedlings Exposed to Salt Stress

PubMed Central

Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Background Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many “biological processes” were affected by salt stress, particular those categories belong to “metabolic process”, such as “primary metabolism process”, “cellular metabolism process” and “macromolecule metabolism process”. The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. Conclusions/Significance The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future. PMID:24837971

A Variable Active Site Residue Influences the Kinetics of Response Regulator Phosphorylation and Dephosphorylation.

PubMed

Immormino, Robert M; Silversmith, Ruth E; Bourret, Robert B

2016-10-04

Two-component regulatory systems, minimally composed of a sensor kinase and a response regulator protein, are common mediators of signal transduction in microorganisms. All response regulators contain a receiver domain with conserved active site residues that catalyze the signal activating and deactivating phosphorylation and dephosphorylation reactions. We explored the impact of variable active site position T+1 (one residue C-terminal to the conserved Thr/Ser) on reaction kinetics and signaling fidelity, using wild type and mutant Escherichia coli CheY, CheB, and NarL to represent the three major sequence classes observed across response regulators: Ala/Gly, Ser/Thr, and Val/Ile/Met, respectively, at T+1. Biochemical and structural data together suggested that different amino acids at T+1 impacted reaction kinetics by altering access to the active site while not perturbing overall protein structure. A given amino acid at position T+1 had similar effects on autodephosphorylation in each protein background tested, likely by modulating access of the attacking water molecule to the active site. Similarly, rate constants for CheY autophosphorylation with three different small molecule phosphodonors were consistent with the steric constraints on access to the phosphorylation site arising from combination of specific phosphodonors with particular amino acids at T+1. Because other variable active site residues also influence response regulator phosphorylation biochemistry, we began to explore how context (here, the amino acid at T+2) affected the influence of position T+1 on CheY autocatalytic reactions. Finally, position T+1 affected the fidelity and kinetics of phosphotransfer between sensor kinases and response regulators but was not a primary determinant of their interaction.

Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress.

PubMed

Zhang, Lin; Zhang, Chao; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future.

The proteome: structure, function and evolution

PubMed Central

Fleming, Keiran; Kelley, Lawrence A; Islam, Suhail A; MacCallum, Robert M; Muller, Arne; Pazos, Florencio; Sternberg, Michael J.E

2006-01-01

This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk. Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein (http://www.e-protein.org/). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family. PMID:16524832

Revitalizing problem based learning: student and tutor attitudes towards a structured tutorial.

PubMed

Espey, Eve; Ogburn, Tony; Kalishman, Summers; Zsemlye, Meggan; Cosgrove, Ellen

2007-03-01

The pre-clinical curriculum at the University of New Mexico School of Medicine is a hybrid model that includes small group, problem-based learning (PBL) tutorials and didactic lectures. A structured tutorial format was piloted for the human sexuality/reproduction organ system block for the PBL component. The objective of this study was to compare the acceptability of the structured format and its effectiveness with that of a traditional PBL tutorial. Students were surveyed after the renal/endocrinology block of 2004 (traditional tutorial format) and after the human sexuality/reproduction block of 2004 (structured tutorial format) (n = 70). Survey questions covered the quality of learning and of tutorial. Students (n = 132) and tutors (n = 24) who participated in human sexuality/reproduction in 2004 and 2005 were surveyed for attitudes about the structured tutorial overall and specific components. Means of responses were compared using t-tests. Students indicated that the structured tutorial format supported a greater improvement in their basic science and clinical knowledge and their ability to evaluate information (p < 0.05). The majority of students and tutors recommended the structured format for tutorials in other blocks. We demonstrated the acceptability of a structured tutorial format to students and faculty. Faculty members perceived greater depth of learning and participation by the students.

Oleamide derivatives are prototypical anti-metastasis drugs that act by inhibiting Connexin 26.

PubMed

Nojima, Hiroshi; Ohba, Yusuke; Kita, Yasuyuki

2007-09-01

Despite considerable research, metastasis remains a major challenge in the clinical management of cancer. Recent reports show that abnormally augmented expression of Cx26 is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells. The function of Cx26 appears to be responsible for this phenotype since exogenous expression of a dominant-negative form of Cx26 and oleamide derivatives called MI-18 and MI-22 that specifically inhibit Cx26-mediated gap junction-mediated intercellular communications (GJIC) prevent the spontaneous metastasis of BL6 cells. As expected from their structural similarity to oleic acid (the major component of olive oil), both MI-18 and MI-22 are safe drugs; nonetheless, they are potent inhibitors of the spontaneous metastasis of BL6 mouse melanoma cells. Thus, they are a novel prototype of an anti-metastasis drug that has minimal side effects. While the primary tumors do not necessarily show strong Cx26-immunostaining signals, pronounced Cx26 expression is detected in the highly invasive tumor regions; it is also more frequently observed in metastasized tumors. Thus, Cx26 expression may be useful as a prognostic tool that can predict the existence of highly metastatic cancer cells in clinical samples.

Content of antioxidative caffeoylquinic acid derivatives in field-grown Ligularia fischeri (Ledeb.) Turcz and responses to sunlight.

PubMed

Kim, Sang Min; Jeon, Je-Seung; Kang, Suk Woo; Jung, Yu-Jin; Ly, Lin Na; Um, Byung-Hun

2012-06-06

Ligularia fischeri (Ledeb.) Turcz, a commercial leafy vegetable, contains caffeoylquinic acid derivatives (CQAs) as major phenolic constituents. The HPLC chromatograms of leaf extracts collected from different areas in Korea showed a significant variation in CQA amount, and two tri-O-caffeoylquinic acids (triCQAs) were purified and structurally identified by NMR and MS from this plant. Radical scavenging activities among CQAs were found to be increased in proportion to the number of caffeoyl groups. Since this plant prefers damp and shady growth conditions, the effects of sunlight were investigated by growing plantlets in sunlight and shade for four weeks. Greater leaf thickness and higher phenolic contents were found for leaves grown in sunlight than in shade. Four major CQAs-5-mono-O-caffeoylquinic acid (5-monoCQA), and 3,4-, 3,5-, and 4,5-di-O-caffeoylquinic acid (diCQA)-were induced by solar irradiation, whereas the content of these compounds decreased steadily in shade leaves. The leaves of L. fischeri clearly showed adaptation responses to sunlight, and these characteristics can be exploited for cultivation of this plant for potential use as a nutraceutical and functional food.

Examining Gender Differences in Written Assessment Tasks in Biology: A Case Study of Evolutionary Explanations

PubMed Central

Federer, Meghan Rector; Nehm, Ross H.; Pearl, Dennis K.

2016-01-01

Understanding sources of performance bias in science assessment provides important insights into whether science curricula and/or assessments are valid representations of student abilities. Research investigating assessment bias due to factors such as instrument structure, participant characteristics, and item types are well documented across a variety of disciplines. However, the relationships among these factors are unclear for tasks evaluating understanding through performance on scientific practices, such as explanation. Using item-response theory (Rasch analysis), we evaluated differences in performance by gender on a constructed-response (CR) assessment about natural selection (ACORNS). Three isomorphic item strands of the instrument were administered to a sample of undergraduate biology majors and nonmajors (Group 1: n = 662 [female = 51.6%]; G2: n = 184 [female = 55.9%]; G3: n = 642 [female = 55.1%]). Overall, our results identify relationships between item features and performance by gender; however, the effect is small in the majority of cases, suggesting that males and females tend to incorporate similar concepts into their CR explanations. These results highlight the importance of examining gender effects on performance in written assessment tasks in biology. PMID:26865642

Suites of Terpene Synthases Explain Differential Terpenoid Production in Ginger and Turmeric Tissues

PubMed Central

Koo, Hyun Jo; Gang, David R.

2012-01-01

The essential oils of ginger (Zingiber officinale) and turmeric (Curcuma longa) contain a large variety of terpenoids, some of which possess anticancer, antiulcer, and antioxidant properties. Despite their importance, only four terpene synthases have been identified from the Zingiberaceae family: (+)-germacrene D synthase and (S)-β-bisabolene synthase from ginger rhizome, and α-humulene synthase and β-eudesmol synthase from shampoo ginger (Zingiber zerumbet) rhizome. We report the identification of 25 mono- and 18 sesquiterpene synthases from ginger and turmeric, with 13 and 11, respectively, being functionally characterized. Novel terpene synthases, (−)-caryolan-1-ol synthase and α-zingiberene/β-sesquiphellandrene synthase, which is responsible for formation of the major sesquiterpenoids in ginger and turmeric rhizomes, were also discovered. These suites of enzymes are responsible for formation of the majority of the terpenoids present in these two plants. Structures of several were modeled, and a comparison of sets of paralogs suggests how the terpene synthases in ginger and turmeric evolved. The most abundant and most important sesquiterpenoids in turmeric rhizomes, (+)-α-turmerone and (+)-β-turmerone, are produced from (−)-α-zingiberene and (−)-β-sesquiphellandrene, respectively, via α-zingiberene/β-sesquiphellandrene oxidase and a still unidentified dehydrogenase. PMID:23272109

Scale-Dependence of Processes Structuring Dung Beetle Metacommunities Using Functional Diversity and Community Deconstruction Approaches

PubMed Central

da Silva, Pedro Giovâni; Hernández, Malva Isabel Medina

2015-01-01

Community structure is driven by mechanisms linked to environmental, spatial and temporal processes, which have been successfully addressed using metacommunity framework. The relative importance of processes shaping community structure can be identified using several different approaches. Two approaches that are increasingly being used are functional diversity and community deconstruction. Functional diversity is measured using various indices that incorporate distinct community attributes. Community deconstruction is a way to disentangle species responses to ecological processes by grouping species with similar traits. We used these two approaches to determine whether they are improvements over traditional measures (e.g., species composition, abundance, biomass) for identification of the main processes driving dung beetle (Scarabaeinae) community structure in a fragmented mainland-island landscape in southern Brazilian Atlantic Forest. We sampled five sites in each of four large forest areas, two on the mainland and two on the island. Sampling was performed in 2012 and 2013. We collected abundance and biomass data from 100 sampling points distributed over 20 sampling sites. We studied environmental, spatial and temporal effects on dung beetle community across three spatial scales, i.e., between sites, between areas and mainland-island. The γ-diversity based on species abundance was mainly attributed to β-diversity as a consequence of the increase in mean α- and β-diversity between areas. Variation partitioning on abundance, biomass and functional diversity showed scale-dependence of processes structuring dung beetle metacommunities. We identified two major groups of responses among 17 functional groups. In general, environmental filters were important at both local and regional scales. Spatial factors were important at the intermediate scale. Our study supports the notion of scale-dependence of environmental, spatial and temporal processes in the distribution and functional organization of Scarabaeinae beetles. We conclude that functional diversity may be used as a complementary approach to traditional measures, and that community deconstruction allows sufficient disentangling of responses of different trait-based groups. PMID:25822150

Structural and immunologic correlates of chemically stabilized HIV-1 envelope glycoproteins

PubMed Central

de Val, Natalia; Montefiori, David; Tomaras, Georgia D.; Shen, Xiaoying; Kalyuzhniy, Oleksandr; Sanders, Rogier W.; McCoy, Laura E.; Moore, John P.; Ward, Andrew B.

2018-01-01

Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used for vaccine antigen stabilization, but how this process affects structure, antigenicity and immunogenicity is poorly understood and its use remains entirely empirical. We have solved the first cryo-EM structure of a cross-linked vaccine antigen. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a CD4 binding site-specific broadly neutralizing antibody (bNAb) Fab fragment reveals how cross-linking affects key properties of the trimer. We observed density corresponding to highly specific glutaraldehyde (GLA) cross-links between gp120 monomers at the trimer apex and between gp120 and gp41 at the trimer interface that had strikingly little impact on overall trimer conformation, but critically enhanced trimer stability and improved Env antigenicity. Cross-links were also observed within gp120 at sites associated with the N241/N289 glycan hole that locally modified trimer antigenicity. In immunogenicity studies, the neutralizing antibody response to cross-linked trimers showed modest but significantly greater breadth against a global panel of difficult-to-neutralize Tier-2 heterologous viruses. Moreover, the specificity of autologous Tier-2 neutralization was modified away from the N241/N289 glycan hole, implying a novel specificity. Finally, we have investigated for the first time T helper cell responses to next-generation soluble trimers, and report on vaccine-relevant immunodominant responses to epitopes within BG505 that are modified by cross-linking. Elucidation of the structural correlates of a cross-linked viral glycoprotein will allow more rational use of this methodology for vaccine design, and reveals a strategy with promise for eliciting neutralizing antibodies needed for an effective HIV-1 vaccine. PMID:29746590

Differing growth responses of major phylogenetic groups of marine bacteria to natural phytoplankton blooms in the western North Pacific Ocean.

PubMed

Tada, Yuya; Taniguchi, Akito; Nagao, Ippei; Miki, Takeshi; Uematsu, Mitsuo; Tsuda, Atsushi; Hamasaki, Koji

2011-06-01

Growth and productivity of phytoplankton substantially change organic matter characteristics, which affect bacterial abundance, productivity, and community structure in aquatic ecosystems. We analyzed bacterial community structures and measured activities inside and outside phytoplankton blooms in the western North Pacific Ocean by using bromodeoxyuridine immunocytochemistry and fluorescence in situ hybridization (BIC-FISH). Roseobacter/Rhodobacter, SAR11, Betaproteobacteria, Alteromonas, SAR86, and Bacteroidetes responded differently to changes in organic matter supply. Roseobacter/Rhodobacter bacteria remained widespread, active, and proliferating despite large fluctuations in organic matter and chlorophyll a (Chl-a) concentrations. The relative contribution of Bacteroidetes to total bacterial production was consistently high. Furthermore, we documented the unexpectedly large contribution of Alteromonas to total bacterial production in the bloom. Bacterial abundance, productivity, and growth potential (the proportion of growing cells in a population) were significantly correlated with Chl-a and particulate organic carbon concentrations. Canonical correspondence analysis showed that organic matter supply was critical for determining bacterial community structures. The growth potential of each bacterial group as a function of Chl-a concentration showed a bell-shaped distribution, indicating an optimal organic matter concentration to promote growth. The growth of Alteromonas and Betaproteobacteria was especially strongly correlated with organic matter supply. These data elucidate the distinctive ecological role of major bacterial taxa in organic matter cycling during open ocean phytoplankton blooms.

Differing Growth Responses of Major Phylogenetic Groups of Marine Bacteria to Natural Phytoplankton Blooms in the Western North Pacific Ocean ▿ †

PubMed Central

Tada, Yuya; Taniguchi, Akito; Nagao, Ippei; Miki, Takeshi; Uematsu, Mitsuo; Tsuda, Atsushi; Hamasaki, Koji

2011-01-01

Growth and productivity of phytoplankton substantially change organic matter characteristics, which affect bacterial abundance, productivity, and community structure in aquatic ecosystems. We analyzed bacterial community structures and measured activities inside and outside phytoplankton blooms in the western North Pacific Ocean by using bromodeoxyuridine immunocytochemistry and fluorescence in situ hybridization (BIC-FISH). Roseobacter/Rhodobacter, SAR11, Betaproteobacteria, Alteromonas, SAR86, and Bacteroidetes responded differently to changes in organic matter supply. Roseobacter/Rhodobacter bacteria remained widespread, active, and proliferating despite large fluctuations in organic matter and chlorophyll a (Chl-a) concentrations. The relative contribution of Bacteroidetes to total bacterial production was consistently high. Furthermore, we documented the unexpectedly large contribution of Alteromonas to total bacterial production in the bloom. Bacterial abundance, productivity, and growth potential (the proportion of growing cells in a population) were significantly correlated with Chl-a and particulate organic carbon concentrations. Canonical correspondence analysis showed that organic matter supply was critical for determining bacterial community structures. The growth potential of each bacterial group as a function of Chl-a concentration showed a bell-shaped distribution, indicating an optimal organic matter concentration to promote growth. The growth of Alteromonas and Betaproteobacteria was especially strongly correlated with organic matter supply. These data elucidate the distinctive ecological role of major bacterial taxa in organic matter cycling during open ocean phytoplankton blooms. PMID:21515719

Monoterpenic aldehydes as potential anti-Leishmania agents: activity of Cymbopogon citratus and citral on L. infantum, L. tropica and L. major.

PubMed

Machado, M; Pires, P; Dinis, A M; Santos-Rosa, M; Alves, V; Salgueiro, L; Cavaleiro, C; Sousa, M C

2012-03-01

In order to contribute for the search of new drugs for leishmaniasis, we study the susceptibility of Leishmania infantum, Leishmania tropica and Leishmania major to Cymbopogon citratus essential oil and major compounds, mrycene and citral. C. citratus and citral were the most active inhibiting L. infantum, L. tropica and L. major growth at IC(50) concentrations ranging from 25 to 52 μg/ml and from 34 to 42 μg/ml, respectively. L. infantum promastigotes exposed to essential oil and citral underwent considerable ultrastructural alterations, namely mitochondrial and kinetoplast swelling, autophagosomal structures, disruption of nuclear membrane and nuclear chromatin condensation. C. citratus essential oil and citral promoted the leishmanicidal effect by triggering a programmed cell death. In fact, the leishmanicidal activity was mediated via apoptosis as evidenced by externalization of phosphatidylserine, loss of mitochondrial membrane potential, and cell-cycle arrest at the G(0)/G(1) phase. Taken together, ours findings lead us to propose that citral was responsible for anti-Leishmania activity of the C. citratus and both may represent a valuable source for therapeutic control of leishmaniasis. Copyright © 2011 Elsevier Inc. All rights reserved.

Immunological Characterization of Intraocular Lymphoid Follicles in a Spontaneous Recurrent Uveitis Model.

PubMed

Kleinwort, Kristina J H; Amann, Barbara; Hauck, Stefanie M; Feederle, Regina; Sekundo, Walter; Deeg, Cornelia A

2016-08-01

Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues. Ectopic lymphoid tissues were located preferentially in the iris, ciliary body, and retina at the ora serrata of horses with naturally-occurring ERU. The majority of cells in the tertiary lymphoid follicles were T cells with a scattered distribution of B cells and PNA+ cells interspersed. A fraction of T cells was additionally positive for memory cell marker CD45RO. Almost all cells coexpressed CD166, a molecule associated with activation and transmigration of T cells into inflamed tissues. Several transcription factors that govern immune cell responses were detectable in the tertiary lymphoid follicles, among them Zap70, TFIIB, GATA3, and IRF4. A high expression of the phosphorylated signal transducers and activators of transcription (STAT) proteins 1 and 5 were found at the margin of the structures. Cellular composition and structural organization of these inflammation-associated tertiary lymphoid tissue structures and the expression of markers of matured T and B cells point to highly organized adaptive immune responses in these follicles in spontaneous recurrent uveitis.

Structure-based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies*

PubMed Central

Kesavardhana, Sannula; Das, Raksha; Citron, Michael; Datta, Rohini; Ecto, Linda; Srilatha, Nonavinakere Seetharam; DiStefano, Daniel; Swoyer, Ryan; Joyce, Joseph G.; Dutta, Somnath; LaBranche, Celia C.; Montefiori, David C.; Flynn, Jessica A.; Varadarajan, Raghavan

2017-01-01

A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bNAbs isolated from infected individuals. Nonetheless, all trimeric and monomeric Env immunogens designed to date have failed to elicit such antibodies. We report the structure-guided design of HIV-1 cyclically permuted gp120 that forms homogeneous, stable trimers, and displays enhanced binding to multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128, and the quaternary epitope-specific bNAbs PGT145 and PGDM1400. Constructs that were cyclically permuted in the V1 loop region and contained an N-terminal trimerization domain to stabilize V1V2-mediated quaternary interactions, showed the highest homogeneity and the best antigenic characteristics. In guinea pigs, a DNA prime-protein boost regimen with these new gp120 trimer immunogens elicited potent neutralizing antibody responses against highly sensitive Tier 1A isolates and weaker neutralizing antibody responses with an average titer of about 115 against a panel of heterologous Tier 2 isolates. A modest fraction of the Tier 2 virus neutralizing activity appeared to target the CD4 binding site on gp120. These results suggest that cyclically permuted HIV-1 gp120 trimers represent a viable platform in which further modifications may be made to eventually achieve protective bNAb responses. PMID:27879316

Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

NASA Technical Reports Server (NTRS)

Globus, Ruth K.; Searby, Nancy D.; Almeida, Eduardo A. C.; Sutijono, Darrell; Yu, Joon-Ho; Malouvier, Alexander; Doty, Steven B.; Morey-Holton, Emily; Weinstein, Steven L.; Dalton, Bonnie P. (Technical Monitor)

2000-01-01

Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We examined cell survival, reasoning that osteoblasts might mold skeletal structure in a hypergravity environment in part by regulating apoptosis and thus the duration of osteoblast productivity. Finally, we tested the influence of centrifugation on microbial activation of a macrophage cell line (RAW264.7). In response to the appropriate hormonal stimulation, this cell line is reportedly capable of undergoing differentiation to express osteoclast markers. In addition, a component of the cell wall of gram-negative bacteria, lipopolysaccaride (LPS), stimulates the formation of osteoclasts in vivo. Thus we tested the influence on centrifugation on RAW264.7 cells stimulated with LPS to provide an index of the function of osteoclast precursors.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

PubMed

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

Evaluating the Psychometric Properties and Responsiveness to Change of 3 Depression Measures in a Sample of Persons With Traumatic Spinal Cord Injury and Major Depressive Disorder.

PubMed

Williams, Ryan T; Heinemann, Allen W; Neumann, Holly Demark; Fann, Jesse R; Forchheimer, Martin; Richardson, Elizabeth J; Bombardier, Charles H

2016-06-01

To compare the measurement properties and responsiveness to change of the Patient Health Questionnaire-9 (PHQ-9), the Hopkins Symptom Checklist-20 (HSCL-20), and the Hamilton Depression Rating Scale (HAM-D) in people with spinal cord injury (SCI) diagnosed with major depressive disorder (MDD). Secondary analysis of depression symptoms measured at 6 occasions over 12 weeks as part of a randomized controlled trial of venlafaxine XR for MDD in persons with SCI. Outpatient and community settings. Individuals (N=133) consented and completed the drug trial. Eligibility criteria were age at least 18 years, traumatic SCI, and diagnosis of MDD. Venlafaxine XR. Patients completed the PHQ-9 and the HSCL-20 depression scales; clinical investigators completed the HAM-D and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) Dissociative Disorders, which was used as a diagnostic criterion measure. All 3 instruments were improved with rating scale analysis. The HSCL-20 and the HAM-D contained items that misfit the underlying construct and that correlated weakly with the total scores. Removing these items improved the internal consistency, with floor effects increasing slightly. The HAM-D correlated most strongly with Structured Clinical Interview for DSM-IV Dissociative Disorders diagnoses. Improvement in depression was similar on all outcome measures in both treatment and control groups. The psychometric properties of the revised depression instruments are more than adequate for routine use in adults with SCI and are responsive to clinical improvement. The PHQ-9 is the simplest instrument with measurement properties as good as or better than those of the other instruments and required the fewest modifications. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Brain circuitries involved in emotional interference task in major depression disorder.

PubMed

Chechko, Natalia; Augustin, Marc; Zvyagintsev, Michael; Schneider, Frank; Habel, Ute; Kellermann, Thilo

2013-07-01

Emotional and non-emotional Stroop are frequently applied to study major depressive disorder (MDD). The versions of emotional Stroop used in previous studies were not, unlike the ones employed in the present study, based on semantic incongruence, making it difficult to compare the tasks. We used functional magnetic resonance imaging (fMRI) to study the neural and behavioral responses of 18 healthy subjects and 18 subjects with MDD to emotional and non-emotional word-face Stroop tasks based on semantic incompatibility between targets and distractors. In both groups, the distractors triggered significant amounts of interference conflict. A between-groups comparison revealed hypoactivation in MDD during emotional task in areas supporting conflict resolution (lateral prefrontal cortex, parietal and extrastriate cortices) paralleled by increased response in the right amygdala. Response in the amygdala, however, did not vary between conflicting and non-conflicting trials. While in the emotional (compared to non-emotional) task healthy controls showed considerably stronger involvement of networks related to conflict resolution, in patients, the processing differences between the two conflict types were negligible. The patients group was inhomogeneous in terms of medication and clinical characteristics. The number of female participants was higher, due to which gender effects could not be studied or excluded. Whilst healthy controls seemed able to adjust the involvement of the network supporting conflict resolution based on conflict demand, patients appeared to lack this capability. The reduced cortical involvement coupled with increased response of limbic structures might underlie the maladjustment vis-à-vis new demands in depressed mood. Copyright © 2013 Elsevier B.V. All rights reserved.

Fasting induces a biphasic adaptive metabolic response in murine small intestine

PubMed Central

Sokolović, Milka; Wehkamp, Diederik; Sokolović, Aleksandar; Vermeulen, Jacqueline; Gilhuijs-Pederson, Lisa A; van Haaften, Rachel IM; Nikolsky, Yuri; Evelo, Chris TA; van Kampen, Antoine HC; Hakvoort, Theodorus BM; Lamers, Wouter H

2007-01-01

Background The gut is a major energy consumer, but a comprehensive overview of the adaptive response to fasting is lacking. Gene-expression profiling, pathway analysis, and immunohistochemistry were therefore carried out on mouse small intestine after 0, 12, 24, and 72 hours of fasting. Results Intestinal weight declined to 50% of control, but this loss of tissue mass was distributed proportionally among the gut's structural components, so that the microarrays' tissue base remained unaffected. Unsupervised hierarchical clustering of the microarrays revealed that the successive time points separated into distinct branches. Pathway analysis depicted a pronounced, but transient early response that peaked at 12 hours, and a late response that became progressively more pronounced with continued fasting. Early changes in gene expression were compatible with a cellular deficiency in glutamine, and metabolic adaptations directed at glutamine conservation, inhibition of pyruvate oxidation, stimulation of glutamate catabolism via aspartate and phosphoenolpyruvate to lactate, and enhanced fatty-acid oxidation and ketone-body synthesis. In addition, the expression of key genes involved in cell cycling and apoptosis was suppressed. At 24 hours of fasting, many of the early adaptive changes abated. Major changes upon continued fasting implied the production of glucose rather than lactate from carbohydrate backbones, a downregulation of fatty-acid oxidation and a very strong downregulation of the electron-transport chain. Cell cycling and apoptosis remained suppressed. Conclusion The changes in gene expression indicate that the small intestine rapidly looses mass during fasting to generate lactate or glucose and ketone bodies. Meanwhile, intestinal architecture is maintained by downregulation of cell turnover. PMID:17925015

Biological Networks Underlying Abiotic Stress Tolerance in Temperate Crops—A Proteomic Perspective

PubMed Central

Kosová, Klára; Vítámvás, Pavel; Urban, Milan Oldřich; Klíma, Miroslav; Roy, Amitava; Prášil, Ilja Tom

2015-01-01

Abiotic stress factors, especially low temperatures, drought, and salinity, represent the major constraints limiting agricultural production in temperate climate. Under the conditions of global climate change, the risk of damaging effects of abiotic stresses on crop production increases. Plant stress response represents an active process aimed at an establishment of novel homeostasis under altered environmental conditions. Proteins play a crucial role in plant stress response since they are directly involved in shaping the final phenotype. In the review, results of proteomic studies focused on stress response of major crops grown in temperate climate including cereals: common wheat (Triticum aestivum), durum wheat (Triticum durum), barley (Hordeum vulgare), maize (Zea mays); leguminous plants: alfalfa (Medicago sativa), soybean (Glycine max), common bean (Phaseolus vulgaris), pea (Pisum sativum); oilseed rape (Brassica napus); potato (Solanum tuberosum); tobacco (Nicotiana tabaccum); tomato (Lycopersicon esculentum); and others, to a wide range of abiotic stresses (cold, drought, salinity, heat, imbalances in mineral nutrition and heavy metals) are summarized. The dynamics of changes in various protein functional groups including signaling and regulatory proteins, transcription factors, proteins involved in protein metabolism, amino acid metabolism, metabolism of several stress-related compounds, proteins with chaperone and protective functions as well as structural proteins (cell wall components, cytoskeleton) are briefly overviewed. Attention is paid to the differences found between differentially tolerant genotypes. In addition, proteomic studies aimed at proteomic investigation of multiple stress factors are discussed. In conclusion, contribution of proteomic studies to understanding the complexity of crop response to abiotic stresses as well as possibilities to identify and utilize protein markers in crop breeding processes are discussed. PMID:26340626

Fasting induces a biphasic adaptive metabolic response in murine small intestine.

PubMed

Sokolović, Milka; Wehkamp, Diederik; Sokolović, Aleksandar; Vermeulen, Jacqueline; Gilhuijs-Pederson, Lisa A; van Haaften, Rachel I M; Nikolsky, Yuri; Evelo, Chris T A; van Kampen, Antoine H C; Hakvoort, Theodorus B M; Lamers, Wouter H

2007-10-09

The gut is a major energy consumer, but a comprehensive overview of the adaptive response to fasting is lacking. Gene-expression profiling, pathway analysis, and immunohistochemistry were therefore carried out on mouse small intestine after 0, 12, 24, and 72 hours of fasting. Intestinal weight declined to 50% of control, but this loss of tissue mass was distributed proportionally among the gut's structural components, so that the microarrays' tissue base remained unaffected. Unsupervised hierarchical clustering of the microarrays revealed that the successive time points separated into distinct branches. Pathway analysis depicted a pronounced, but transient early response that peaked at 12 hours, and a late response that became progressively more pronounced with continued fasting. Early changes in gene expression were compatible with a cellular deficiency in glutamine, and metabolic adaptations directed at glutamine conservation, inhibition of pyruvate oxidation, stimulation of glutamate catabolism via aspartate and phosphoenolpyruvate to lactate, and enhanced fatty-acid oxidation and ketone-body synthesis. In addition, the expression of key genes involved in cell cycling and apoptosis was suppressed. At 24 hours of fasting, many of the early adaptive changes abated. Major changes upon continued fasting implied the production of glucose rather than lactate from carbohydrate backbones, a downregulation of fatty-acid oxidation and a very strong downregulation of the electron-transport chain. Cell cycling and apoptosis remained suppressed. The changes in gene expression indicate that the small intestine rapidly looses mass during fasting to generate lactate or glucose and ketone bodies. Meanwhile, intestinal architecture is maintained by downregulation of cell turnover.

Joining Chemical Pressure and Epitaxial Strain to Yield Y-doped BiFeO3 Thin Films with High Dielectric Response

PubMed Central

Scarisoreanu, N. D.; Craciun, F.; Birjega, R.; Ion, V.; Teodorescu, V. S.; Ghica, C.; Negrea, R.; Dinescu, M.

2016-01-01

BiFeO3 is one of the most promising multiferroic materials but undergoes two major drawbacks: low dielectric susceptibility and high dielectric loss. Here we report high in-plane dielectric permittivity (ε’ ∼2500) and low dielectric loss (tan δ < 0.01) obtained on Bi0.95Y0.05FeO3 films epitaxially grown on SrTiO3 (001) by pulsed laser deposition. High resolution transmission electron microscopy and geometric phase analysis evidenced nanostripe domains with alternating compressive/tensile strain and slight lattice rotations. Nanoscale mixed phase/domain ensembles are commonly found in different complex materials with giant dielectric/electromechanical (ferroelectric/ relaxors) or magnetoresistance (manganites) response. Our work brings insight into the joined role of chemical pressure and epitaxial strain on the appearance of nanoscale stripe structure which creates conditions for easy reorientation and high dielectric response, and could be of more general relevance for the field of materials science where engineered materials with huge response to external stimuli are a highly priced target. PMID:27157090

Drug allergy

PubMed Central

Warrington, Richard

2012-01-01

Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

The sterile inflammatory response

PubMed Central

Rock, Kenneth L.; Latz, Eicke; Ontiveros, Fernando; Kono, Hajime

2015-01-01

The acute inflammatory response is a double-edged sword. On the one hand it plays a key role in initial host defense particularly against many infections. On the other hand its aim is imprecise and as a consequence, when it is drawn into battle, it can cause collateral damage in tissues. In situations where the inciting stimulus is sterile, the cost-benefit ratio may be high; because of this, sterile inflammation underlies the pathogenesis of a number of diseases. While there have been major advances in our understanding of how microbes trigger inflammation, much less has been learned about this process in sterile situations. This review focuses on a subset of the many sterile stimuli that can induce inflammation – specifically dead cells and a variety of irritant particles, including crystals, minerals, and protein aggregates. Although this subset of stimuli is structurally very diverse and might appear to be unrelated, there is accumulating evidence that the innate immune system may recognize them in similar ways and stimulate the sterile inflammatory response via common pathways. Here we review established and emerging data about these responses. PMID:20307211

Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD Responses during Perception of Dynamic Compared to Static Facial Expressions

PubMed Central

Rymarczyk, Krystyna; Żurawski, Łukasz; Jankowiak-Siuda, Kamila; Szatkowska, Iwona

2018-01-01

Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions. PMID:29467691

Human and Environmental Impacts on River Sediment Microbial Communities

DOE PAGES

Gibbons, Sean M.; Jones, Edwin; Bearquiver, Angelita; ...

2014-05-19

Sediment microbial communities are responsible for a majority of the metabolic activity in river and stream ecosystems. Understanding the dynamics in community structure and function across freshwater environments will help us to predict how these ecosystems will change in response to human land-use practices. Here we present a spatiotemporal study of sediments in the Tongue River (Montana, USA), comprising six sites along 134 km of river sampled in both spring and fall for two years. Sequencing of 16S rRNA amplicons and shotgun metagenomes revealed that these sediments are the richest (~65,000 microbial ‘species’ identified) and most novel (93% of OTUsmore » do not match known microbial diversity) ecosystems analyzed by the Earth Microbiome Project to date, and display more functional diversity than was detected in a recent review of global soil metagenomes. Community structure and functional potential have been significantly altered by anthropogenic drivers, including increased pathogenicity and antibiotic metabolism markers near towns and metabolic signatures of coal and coalbed methane extraction byproducts. The core (OTUs shared across all samples) and the overall microbial community exhibited highly similar structure, and phylogeny was weakly coupled with functional potential. Together, these results suggest that microbial community structure is shaped by environmental drivers and niche filtering, though stochastic assembly processes likely play a role as well. These results indicate that sediment microbial communities are highly complex and sensitive to changes in land use practices.« less

Molecular assessment of microbiota structure and dynamics along mixed olive oil and winery wastewaters biotreatment.

PubMed

Eusébio, Ana; Tacão, Marta; Chaves, Sandra; Tenreiro, Rogério; Almeida-Vara, Elsa

2011-07-01

The major parcel of the degradation occurring along wastewater biotreatments is performed either by the native microbiota or by added microbial inocula. The main aim of this study was to apply two fingerprinting methods, temperature gradient gel electrophoresis (TGGE) and length heterogeneity-PCR (LH-PCR) analysis of 16S rRNA gene fragments, in order to assess the microbiota structure and dynamics during mixed olive oil and winery wastewaters aerobic biotreatment performed in a jet-loop reactor (JLR). Sequence homology analysis showed the presence of bacterial genera Gluconacetobacter, Klebsiella, Lactobacillus, Novosphingobium, Pseudomonas, Prevotella, Ralstonia, Sphingobium and Sphingomonas affiliated with five main phylogenetic groups: alpha-, beta- and gamma-Proteobacteria, Firmicutes and Bacteroidetes. LH-PCR analysis distinguished eight predominant DNA fragments correlated with the samples showing highest performance (COD removal rates of 67 up to 75%). Cluster analysis of both TGGE and LH-PCR fingerprinting profiles established five main clusters, with similarity coefficients higher than 79% (TGGE) and 62% (LH-PCR), and related with hydraulic retention time, indicating that this was the main factor responsible for the shifts in the microbiota structure. Canonical correspondence analysis revealed that changes observed on temperature and O(2) level were also responsible for shifts in microbiota composition. Community level metabolic profile analysis was used to test metabolic activities in samples. Integrated data revealed that the microbiota structure corresponds to bacterial groups with high degradative potential and good suitability for this type of effluents biotreatments.

Photo-sensitive Ge nanocrystal based films controlled by substrate deposition temperature

NASA Astrophysics Data System (ADS)

Stavarache, Ionel; Maraloiu, Valentin Adrian; Negrila, Catalin; Prepelita, Petronela; Gruia, Ion; Iordache, Gheorghe

2017-10-01

Lowering the temperature of crystallization by deposition of thin films on a heated substrate represents the easiest way to find new means to develop and improve new working devices based on nanocrystals embedded in thin films. The improvements are strongly related with the increasing of operation speed, substantially decreasing the energy consumption and reducing unit fabrication costs of the respective semiconductor devices. This approach avoids major problems, such as those related to diffusion or difficulties in controlling nanocrystallites size, which appear during thermal treatments at high temperatures after deposition. This article reports on a significant progress given by structuring Ge nanocrystals (Ge-NCs) embedded in silicon dioxide (SiO2) thin films by heating the substrate at 400 °C during co-deposition of Ge and SiO2 by magnetron sputtering. As a proof-of-concept, a Si/Ge-NCs:SiO2 photo-sensitive structure was fabricated thereof and characterized. The structure shows superior performance on broad operation bandwidth from visible to near-infrared, as strong rectification properties in dark, significant current rise in the inversion mode when illuminated, high responsivity, high photo-detectivity of 1014 Jones, quick response and significant conversion efficiency with peak value reaching 850% at -1 V and about 1000 nm. This simple preparation approach brings an important contribution to the effort of structuring Ge nanocrystallites in SiO2 thin films at a lower temperature for the purpose of using these materials for devices in optoelectronics, solar cells and electronics on flexible substrates.

Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain

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

Tan, Kemin; Deatherage Kaiser, Brooke L.; Wu, Ruiying

S. Typhimurium can induce both humoral and cell-mediated responses when establishing itself in the host. These responses are primarily stimulated against the lipopolysaccharide and major outer membrane (OM) proteins. OmpA is one of these major OM proteins. It comprises a N-terminal eight-stranded b-barrel trans membrane domain and a C-terminal domain (OmpACTD). The OmpACTD and its homologs are believed to bind to peptidoglycan (PG) within the periplasm, maintaining bacterial osmotic homeostasis and modulating the permeability and integrity of the OM. Here we present the first crystal structures of the OmpACTD from two pathogens: S. Typhimurium (STOmpACTD) in open and closed formsmore » and causative agent of Lyme Disease Borrelia burgdorferi (BbOmpACTD), in closed form. In the open form of STOmpACTD, an aspartic acid residue from a long b2-a3 loop points into the binding pocket, suggesting that an anion group such as a carboxylate group from PG is favored at the binding site. In the closed form of STOmpACTD and in the structure of BbOmpACTD, a sulfate group from the crystallization buffer is tightly bound at the binding site. The differences between the closed and open forms of STOmpACTD, suggest a large conformational change that includes an extension of a3 helix by ordering a part of b2-a3 loop. We propose that the sulfate anion observed in these structures mimics the carboxylate group of PG when bound to STOmpACTD suggesting PG-anchoring mechanism. In addition, the binding of PG or a ligand mimic may enhance dimerization of STOmpACTD, or possibly that of full length STOmpA.« less

Structural organisation and lipid composition of the epicuticular accessory layer of infective larvae of Trichinella spiralis.

PubMed

Gounaris, K; Smith, V P; Selkirk, M E

1996-05-22

The epicuticle of infective larvae of Trichinella spiralis represents the interface between this intracellular nematode parasite and the cytosol of mammalian skeletal muscle. The macromolecular structures that make up the epicuticle were studied by freeze-fracture electron microscopy and compositional analysis. Three fracture planes were observed: one with a typical plasma membrane-type bilayer organisation which was overlaid by two extended layers of lipid in an inverted cylindrical configuration. This overall structure remained unchanged in response to variations in temperature between 20 degrees C and 45 degrees C. The lipid cylinders were on average 6.8 nm in diameter, with randomly-associated particles that were not dissociated by high-salt treatment, indicative of hydrophobically associated proteins. The majority of the lipids were non-polar, consisting of cholesterol, cholesterol esters, mono- and tri-glycerides, and free fatty acids. Three major classes of phospholipids were identified: phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. Total lipid extracts did not adopt an inverted cylindrical or micellar configuration on isolation, but formed flat sheets of lamellae as did the purified polar and non-polar fractions of the lipids. Isolated lipids did not undergo thermally-induced polymorphism between 20 degrees C and 60 degrees C and there was no pH dependency of the structures adopted. The fatty acid saturation levels of the phospholipids were compatible with the observation that they did not form polymorphic structures on isolation. We suggest that this unusual configuration is probably stabilised by the associated (glyco)proteins and may be required for selective permeation of nutrients from the host cell cytosol and/or for maintaining the high curvature of the parasite within the cell.

Flavonoids: hemisynthesis, reactivity, characterization and free radical scavenging activity.

PubMed

Es-Safi, Nour-Eddine; Ghidouche, Souhila; Ducrot, Paul Henri

2007-09-26

Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been isolated as pure compounds and their structures unambiguously established through spectroscopic methods. Correlation between the structure of the oxidation product and the substitution pattern of the starting materials allows mechanistic features of this transformation to be elucidated.

Crystal Structures of Wild-type and Mutant Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase Reveal an Alternative Conformation of NADPH that may be Linked to Trimethoprim Resistance

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

Frey, K.; Liu, J; Lombardo, M

2009-01-01

Both hospital- and community-acquired Staphylococcus aureus infections have become major health concerns in terms of morbidity, suffering and cost. Trimethoprim-sulfamethoxazole (TMP-SMZ) is an alternative treatment for methicillin-resistant S. aureus (MRSA) infections. However, TMP-resistant strains have arisen with point mutations in dihydrofolate reductase (DHFR), the target for TMP. A single point mutation, F98Y, has been shown biochemically to confer the majority of this resistance to TMP. Using a structure-based approach, we have designed a series of novel propargyl-linked DHFR inhibitors that are active against several trimethoprim-resistant enzymes. We screened this series against wild-type and mutant (F98Y) S. aureus DHFR and foundmore » that several are active against both enzymes and specifically that the meta-biphenyl class of these inhibitors is the most potent. In order to understand the structural basis of this potency, we determined eight high-resolution crystal structures: four each of the wild-type and mutant DHFR enzymes bound to various propargyl-linked DHFR inhibitors. In addition to explaining the structure-activity relationships, several of the structures reveal a novel conformation for the cofactor, NADPH. In this new conformation that is predominantly associated with the mutant enzyme, the nicotinamide ring is displaced from its conserved location and three water molecules complete a network of hydrogen bonds between the nicotinamide ring and the protein. In this new position, NADPH has reduced interactions with the inhibitor. An equilibrium between the two conformations of NADPH, implied by their occupancies in the eight crystal structures, is influenced both by the ligand and the F98Y mutation. The mutation induced equilibrium between two NADPH-binding conformations may contribute to decrease TMP binding and thus may be responsible for TMP resistance.« less

HMGN proteins modulate chromatin regulatory sites and gene expression during activation of naïve B cells

PubMed Central

Zhang, Shaofei; Zhu, Iris; Deng, Tao; Furusawa, Takashi; Rochman, Mark; Vacchio, Melanie S.; Bosselut, Remy; Yamane, Arito; Casellas, Rafael; Landsman, David; Bustin, Michael

2016-01-01

The activation of naïve B lymphocyte involves rapid and major changes in chromatin organization and gene expression; however, the complete repertoire of nuclear factors affecting these genomic changes is not known. We report that HMGN proteins, which bind to nucleosomes and affect chromatin structure and function, co-localize with, and maintain the intensity of DNase I hypersensitive sites genome wide, in resting but not in activated B cells. Transcription analyses of resting and activated B cells from wild-type and Hmgn−/− mice, show that loss of HMGNs dampens the magnitude of the transcriptional response and alters the pattern of gene expression during the course of B-cell activation; defense response genes are most affected at the onset of activation. Our study provides insights into the biological function of the ubiquitous HMGN chromatin binding proteins and into epigenetic processes that affect the fidelity of the transcriptional response during the activation of B cell lymphocytes. PMID:27112571

Mussel-Inspired Protein Nanoparticles Containing Iron(III)-DOPA Complexes for pH-Responsive Drug Delivery.

PubMed

Kim, Bum Jin; Cheong, Hogyun; Hwang, Byeong Hee; Cha, Hyung Joon

2015-06-15

A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve pH-responsive drug release exploits the pH-dependent changes in the coordination stoichiometry of iron(III)-3,4-dihydroxyphenylalanine (DOPA) complexes, which play a major cross-linking role in mussel byssal threads. Doxorubicin-loaded polymeric NPs that are based on Fe(III)-DOPA complexation were thus synthesized with a DOPA-modified recombinant mussel adhesive protein through a co-electrospraying process. The release of doxorubicin was found to be predominantly governed by a change in the structure of the Fe(III)-DOPA complexes induced by an acidic pH value. It was also demonstrated that the fabricated NPs exhibited effective cytotoxicity towards cancer cells through efficient cellular uptake and cytosolic release. Therefore, it is anticipated that Fe(III)-DOPA complexation can be successfully utilized as a new design principle for pH-responsive NPs for diverse controlled drug-delivery applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectral response data for development of cool coloured tile coverings

NASA Astrophysics Data System (ADS)

Libbra, Antonio; Tarozzi, Luca; Muscio, Alberto; Corticelli, Mauro A.

2011-03-01

Most ancient or traditional buildings in Italy show steep-slope roofs covered by red clay tiles. As the rooms immediately below the roof are often inhabited in historical or densely urbanized centres, the combination of low solar reflectance of tile coverings and low thermal inertia of either wooden roof structures or sub-tile insulation panels makes summer overheating a major problem. The problem can be mitigated by using tiles coated with cool colours, that is colours with the same spectral response of clay tiles in the visible, but highly reflecting in the near infrared range, which includes more than half of solar radiation. Cool colours can yield the same visible aspect of common building surfaces, but higher solar reflectance. Studies aimed at developing cool colour tile coverings for traditional Italian buildings have been started. A few coating solutions with the typical red terracotta colour have been produced and tested in the laboratory, using easily available materials. The spectral response and the solar reflectance have been measured and compared with that of standard tiles.

Forest response and recovery following disturbance in upland forests of the Atlantic Coastal Plain.

PubMed

Schäfer, Karina V R; Renninger, Heidi J; Carlo, Nicholas J; Vanderklein, Dirk W

2014-01-01

Carbon and water cycling of forests contribute significantly to the Earth's overall biogeochemical cycling and may be affected by disturbance and climate change. As a larger body of research becomes available about leaf-level, ecosystem and regional scale effects of disturbances on forest ecosystems, a more mechanistic understanding is developing which can improve modeling efforts. Here, we summarize some of the major effects of physical and biogenic disturbances, such as drought, prescribed fire, and insect defoliation, on leaf and ecosystem-scale physiological responses as well as impacts on carbon and water cycling in an Atlantic Coastal Plain upland oak/pine and upland pine forest. During drought, stomatal conductance and canopy stomatal conductance were reduced, however, defoliation increased conductance on both leaf-level and canopy scale. Furthermore, after prescribed fire, leaf-level stomatal conductance was unchanged for pines but decreased for oaks, while canopy stomatal conductance decreased temporarily, but then rebounded the following growing season, thus exhibiting transient responses. This study suggests that forest response to disturbance varies from the leaf to ecosystem level as well as species level and thus, these differential responses interplay to determine the fate of forest structure and functioning post disturbance.

Improving the seismic torsional behavior of plan-asymmetric, single-storey, concrete moment resisting buildings with fluid viscous dampers

NASA Astrophysics Data System (ADS)

Rofooei, Fayaz Rahimzadeh; Mohammadzadeh, Sahar

2016-03-01

The optimal distribution of fluid viscous dampers (FVD) in controlling the seismic response of eccentric, single-storey, moment resisting concrete structures is investigated using the previously defined center of damping constant (CDC). For this purpose, a number of structural models with different one-way stiffness and strength eccentricities are considered. Extensive nonlinear time history analyses are carried out for various arrangements of FVDs. It is shown that the arrangement of FVDs for controlling the torsional behavior due to asymmetry in the concrete structures is very dependent on the intensity of the peak ground acceleration (PGA) and the extent of the structural stiffness and strength eccentricities. The results indicate that, in the linear range of structural behavior the stiffness eccentricity es which is the main parameter in determining the location of optimal CDC, is found to be less or smaller than the optimal damping constant eccentricity e*d, i.e., |e*d| > |es|. But, in the nonlinear range of structural behavior where the strength eccentricity er is the dominant factor in determining the location of optimal CDC, |e*d| > |er|. It is also concluded that for the majority of the plan-asymmetric, concrete structures considered in this study with er ≠ 0, the optimal CDC approaches the center of mass as er decreases.

A structural transect across the Mongolian Western Altai: Active transpressional mountain building in central Asia

NASA Astrophysics Data System (ADS)

Dickson Cunningham, W.; Windley, Brian F.; Dorjnamjaa, D.; Badamgarov, G.; Saandar, M.

1996-02-01

We present results from the first detailed geological transect across the Mongolian Western Altai using modern methods of structural geology and fault kinematic analysis. Our purpose was to document the structures responsible for Cenozoic uplift of the range in order to better understand processes of intracontinental mountain building. Historical right-lateral strike-slip and oblique-slip earthquakes have previously been documented from the Western Altai, and many mountain fronts are marked by active fault scarps indicating current tectonic activity and uplift. The dominant structures in the range are long (>200 km) NNW trending right-lateral strike-slip faults. Our transect can be divided into three separate domains that contain active, right-lateral strike-slip master faults and thrust faults with opposing vergence. The current deformation regime is thus transpressional. Each domain has an asymmetric flower structure cross-sectional geometry, and the transect as a whole is interpreted as three separate large flower structures. The mechanism of uplift along the transect appears to be horizontal and vertical growth of flower structures rooted into the dominant right-lateral strike-slip faults. The major Bulgan Fault forms the southern structural boundary to the range and is a 3.5-km-wide brittle-ductile zone that has accommodated reverse and left-lateral strike-slip displacements. It appears to be linked to the North Gobi Fault Zone to the east and Irtysh Fault zone to the west and thus may be over 900 km in length. Two major ductile left-lateral extensional shear zones were identified in the interior of the range that appear to be preserved structures related to a regional Paleozoic or Mesozoic extensional event. Basement rocks along the transect are dominantly metavolcanic, metasedimentary, or intrusive units probably representing a Paleozoic accretionary prism and arc complex. The extent to which Cenozoic uplift has been accommodated by reactivation of older structures and inversion of older basins is unknown and will require further study. As previously suggested by others, Cenozoic uplift of the Altai is interpreted to be due to NE-SW directed compressional stress resulting from the Indo-Eurasian collision 2500 km to the south.

St. Petersburg Coastal and Marine Science Center coral reef research

USGS Publications Warehouse

Poore, Richard Z.; Kuffner, Ilsa B.; Kellogg, Christina A.

2010-01-01

The U.S. Geological Survey (USGS) Coral Reef Ecosystem STudies (CREST) Project specifically addresses priorities identified in the 'Facing tomorrow's challenges' U.S. Geological Survey science in the decade 2007-2017' document (USGS, 2007). Research includes a blend of historical, monitoring, and process studies aimed at improving our understanding of the development, current status and function, as well as likely future changes in coral ecosystems. Topics such as habitat characterization and distribution, coral disease, and trends in biogenic calcification are major focus areas. We seek to increase the understanding of reef structure, ecological integrity, and responses to global change.

Critical incidents in nursing academics: discovering a new identity.

PubMed

Aguayo-González, Mariela; Castelló-Badía, Montserrat; Monereo-Font, Carles

2015-01-01

a qualitative study that followed the principles of the grounded theory in order to analyze the professional identity of nursing academics through the analysis of the most disturbing critical incidents. semi-structured interviews were conducted with seven nurses who worked as professors and researchers in a private university in Barcelona. the resulting empirical material was organized into two categories: characterization of critical incidents and responsiveness to the incident. the professional identity of nurses regarding the academic area is still under construction and inexperience is the major obstacle in the management of critical incidents in the teaching career.

STS-1 Pogo analysis

NASA Technical Reports Server (NTRS)

1981-01-01

Some of the pogo related data from STS-1 are documented. The measurements and data reduction are described. In the data analysis reference is made to FRF and single engine test results. The measurements are classified under major project elements of the space shuttle main engine, the external tank, and the orbiter. The subsystems are structural dynamics and main propulsion. Data were recorded onboard the orbiter with a minimum response rate of 1.5 to 50 Hz. The wideband, 14 track recorder was used, and the data required demultiplexing before reduction. The flight phase of interest was from liftoff through main engine cutoff.

Chemical and Biological Mobile Laboratory: infrastructure employed by Brazilian Army in emergency response actions

NASA Astrophysics Data System (ADS)

Cardozo, M.; Oliveira, V. G. M.; Sousa, R. B.; de Paula, R. L.

2018-03-01

The Brazilian Army specified and acquired a mobile chemical and biological laboratory in order to confirm in a fast and mobile way with more precise analytical techniques the information obtained by the emergency responders field teams. The laboratory was designed for displacement in different scenarios of the national territory. This paper describes the laboratorial structure, the material flow and the deployment of this defense product in the major international events occurred in Brazil from 2011 to 2016, with the objective of providing in situ identification of chemical and biological threats.

A Gimbal sizing analysis for an IPACS rotating assembly

NASA Technical Reports Server (NTRS)

Burke, P. R.; Coronato, P. A.

1985-01-01

All major components of an integrated power/attitude control system (IPACS) assembly were analyzed for testing, launch, and operational stresses. The conceptual design for the outer gimbal and mounting ring structures were developed and analyzed along with preliminary designs of the pivot and torquer assemblies. Results from the system response analysis and the thermal analysis are also presented. Gimballing of this rotating assembly should present few difficulties as the maximum gimballing rate is quite low. However, the inner gimbal assembly in its current configuration must be modified to develop the system from a laboratory concept to a realistic flight hardware status.

Structural modal parameter identification using local mean decomposition

NASA Astrophysics Data System (ADS)

Keyhani, Ali; Mohammadi, Saeed

2018-02-01

Modal parameter identification is the first step in structural health monitoring of existing structures. Already, many powerful methods have been proposed for this concept and each method has some benefits and shortcomings. In this study, a new method based on local mean decomposition is proposed for modal identification of civil structures from free or ambient vibration measurements. The ability of the proposed method was investigated using some numerical studies and the results compared with those obtained from the Hilbert-Huang transform (HHT). As a major advantage, the proposed method can extract natural frequencies and damping ratios of all active modes from only one measurement. The accuracy of the identified modes depends on their participation in the measured responses. Nevertheless, the identified natural frequencies have reasonable accuracy in both cases of free and ambient vibration measurements, even in the presence of noise. The instantaneous phase angle and the natural logarithm of instantaneous amplitude curves obtained from the proposed method have more linearity rather than those from the HHT algorithm. Also, the end effect is more restricted for the proposed method.

Collagen and the myocardium: fibrillar structure, biosynthesis and degradation in relation to hypertrophy and its regression.

PubMed

Eghbali, M; Weber, K T

1990-07-17

The extracellular matrix of the myocardium contains an elaborate structural matrix composed mainly of fibrillar types I and III collagen. This matrix is responsible for the support and alignment of myocytes and capillaries. Because of its alignment, location, configuration and tensile strength, relative to cardiac myocytes, the collagen matrix represents a major determinant of myocardial stiffness. Cardiac fibroblasts, not myocytes, contain the mRNA for these fibrillar collagens. In the hypertrophic remodeling of the myocardium that accompanies arterial hypertension, a progressive structural and biochemical remodeling of the matrix follows enhanced collagen gene expression. The resultant significant accumulation of collagen in the interstitium and around intramyocardial coronary arteries, or interstitial and perivascular fibrosis, represents a pathologic remodeling of the myocardium that compromises this normally efficient pump. This report reviews the structural nature, biosynthesis and degradation of collagen in the normal and hypertrophied myocardium. It suggests that interstitial heart disease, or the disproportionate growth of the extracellular matrix relative to myocyte hypertrophy, is an entity that merits greater understanding, particularly the factors regulating types I and III collagen gene expression and their degradation.

The middeck 0-gravity dynamics experiment

NASA Technical Reports Server (NTRS)

Crawley, Edward F.; Vanschoor, Marthinus C.; Bokhour, Edward B.

1993-01-01

The Middeck 0-Gravity Dynamics Experiment (MODE), flown onboard the Shuttle STS-48 Mission, consists of three major elements: the Experiment Support Module, a dynamics test bed providing computer experiment control, analog signal conditioning, power conditioning, an operator interface consisting of a keypad and display, experiment electrical and thermal control, and archival data storage: the Fluid Test Article assembly, used to investigate the dynamics of fluid-structure interaction in 0-gravity; and the Structural Test Article for investigating the open-loop dynamics of structures in 0-gravity. Deployable, erectable, and rotary modules were assembled to form three one- and two-dimensional structures, in which variations in bracing wire and rotary joint preload could be introduced. Change in linear modal parameters as well as the change in nonlinear nature of the response is examined. Trends in modal parameters are presented as a function of force amplitude, joint preload, and ambient gravity. An experimental study of the lateral slosh behavior of contained fluids is also presented. A comparison of the measured earth and space results identifies and highlights the effects of gravity on the linear and nonlinear slosh behavior of these fluids.

Linking structure and activity in nonlinear spiking networks

PubMed Central

Josić, Krešimir; Shea-Brown, Eric

2017-01-01

Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks’ spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities—including those of different cell types—combine with connectivity to shape population activity and function. PMID:28644840

Crystal Structures of the β2-Adrenergic Receptor

NASA Astrophysics Data System (ADS)

Weis, William I.; Rosenbaum, Daniel M.; Rasmussen, Søren G. F.; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Yao, Xiao-Jie; Day, Peter W.; Parnot, Charles; Fung, Juan J.; Ratnala, Venkata R. P.; Kobilka, Brian K.; Cherezov, Vadim; Hanson, Michael A.; Kuhn, Peter; Stevens, Raymond C.; Edwards, Patricia C.; Schertler, Gebhard F. X.; Burghammer, Manfred; Sanishvili, Ruslan; Fischetti, Robert F.; Masood, Asna; Rohrer, Daniel K.

G protein coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome, and are responsible for the majority of signal transduction events involving hormones and neuro-transmitters across the cell membrane. GPCRs that bind to diffusible ligands have low natural abundance, are relatively unstable in detergents, and display basal G protein activation even in the absence of ligands. To overcome these problems two approaches were taken to obtain crystal structures of the β2-adrenergic receptor (β2AR), a well-characterized GPCR that binds cate-cholamine hormones. The receptor was bound to the partial inverse agonist carazolol and co-crystallized with a Fab made to a three-dimensional epitope formed by the third intracellular loop (ICL3), or by replacement of ICL3 with T4 lysozyme. Small crystals were obtained in lipid bicelles (β2AR-Fab) or lipidic cubic phase (β2AR-T4 lysozyme), and diffraction data were obtained using microfocus technology. The structures provide insights into the basal activity of the receptor, the structural features that enable binding of diffusible ligands, and the coupling between ligand binding and G-protein activation.

The Crystal Structure of the RNA-Dependent RNA Polymerase from Human Rhinovirus: A Dual Function Target for Common Cold Antiviral Therapy

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

Love, Robert A.; Maegley, Karen A.; Yu, Xiu

Human rhinoviruses (HRV), the predominant members of the Picornaviridae family of positive-strand RNA viruses, are the major causative agents of the common cold. Given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) denoted 3D{sup pol}, which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. Here the crystal structures for three viral serotypes (1B, 14, and 16) of HRV 3D{sup pol} have been determined. The three structures are very similar to one another, and tomore » the closely related poliovirus (PV) 3D{sup pol} enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3D{sup pol} provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3D{sup pol} also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.« less

Mathematical modeling of vibration processes in reinforced concrete structures for setting up crack initiation monitoring

NASA Astrophysics Data System (ADS)

Bykov, A. A.; Matveenko, B. P.; Serovaev, G. S.; Shardakov, I. N.; Shestakov, A. P.

2015-03-01

The contemporary construction industry is based on the use of reinforced concrete structures, but emergency situations resulting in fracture can arise in their exploitation. In a majority of cases, reinforced concrete fracture is realized as the process of crack formation and development. As a rule, the appearance of the first cracks does not lead to the complete loss of the carrying capacity but is a fracture precursor. One method for ensuring the safe operation of building structures is based on crack initiation monitoring. A vibration method for the monitoring of reinforced concrete structures is justified in this paper. An example of a reinforced concrete beam is used to consider all stages related to the analysis of the behavior of natural frequencies in the development of a crack-shaped defect and the use of the obtained numerical results for the vibration test method. The efficiency of the method is illustrated by the results of modeling of the physical part of the method related to the analysis of the natural frequency evolution as a response to the impact action in the crack development process.

Comparative interactomics provides evidence for functional specialization of the nuclear pore complex.

PubMed

Obado, Samson O; Field, Mark C; Rout, Michael P

2017-07-04

The core architecture of the eukaryotic cell was established well over one billion years ago, and is largely retained in all extant lineages. However, eukaryotic cells also possess lineage-specific features, frequently keyed to specific functional requirements. One quintessential core eukaryotic structure is the nuclear pore complex (NPC), responsible for regulating exchange of macromolecules between the nucleus and cytoplasm as well as acting as a nuclear organizational hub. NPC architecture has been best documented in one eukaryotic supergroup, the Opisthokonts (e.g. Saccharomyces cerevisiae and Homo sapiens), which although compositionally similar, have significant variations in certain NPC subcomplex structures. The variation of NPC structure across other taxa in the eukaryotic kingdom however, remains poorly understood. We explored trypanosomes, highly divergent organisms, and mapped and assigned their NPC proteins to specific substructures to reveal their NPC architecture. We showed that the NPC central structural scaffold is conserved, likely across all eukaryotes, but more peripheral elements can exhibit very significant lineage-specific losses, duplications or other alterations in their components. Amazingly, trypanosomes lack the major components of the mRNA export platform that are asymmetrically localized within yeast and vertebrate NPCs. Concomitant with this, the trypanosome NPC is ALMOST completely symmetric with the nuclear basket being the only major source of asymmetry. We suggest these features point toward a stepwise evolution of the NPC in which a coating scaffold first stabilized the pore after which selective gating emerged and expanded, leading to the addition of peripheral remodeling machineries on the nucleoplasmic and cytoplasmic sides of the pore.

Redox-active antibiotics control gene expression and community behavior in divergent bacteria.

PubMed

Dietrich, Lars E P; Teal, Tracy K; Price-Whelan, Alexa; Newman, Dianne K

2008-08-29

It is thought that bacteria excrete redox-active pigments as antibiotics to inhibit competitors. In Pseudomonas aeruginosa, the endogenous antibiotic pyocyanin activates SoxR, a transcription factor conserved in Proteo- and Actinobacteria. In Escherichia coli, SoxR regulates the superoxide stress response. Bioinformatic analysis coupled with gene expression studies in P. aeruginosa and Streptomyces coelicolor revealed that the majority of SoxR regulons in bacteria lack the genes required for stress responses, despite the fact that many of these organisms still produce redox-active small molecules, which indicates that redox-active pigments play a role independent of oxidative stress. These compounds had profound effects on the structural organization of colony biofilms in both P. aeruginosa and S. coelicolor, which shows that "secondary metabolites" play important conserved roles in gene expression and development.