Multi-sensor fusion with interacting multiple model filter for improved aircraft position accuracy.

PubMed

Cho, Taehwan; Lee, Changho; Choi, Sangbang

2013-03-27

The International Civil Aviation Organization (ICAO) has decided to adopt Communications, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) as the 21st century standard for navigation. Accordingly, ICAO members have provided an impetus to develop related technology and build sufficient infrastructure. For aviation surveillance with CNS/ATM, Ground-Based Augmentation System (GBAS), Automatic Dependent Surveillance-Broadcast (ADS-B), multilateration (MLAT) and wide-area multilateration (WAM) systems are being established. These sensors can track aircraft positions more accurately than existing radar and can compensate for the blind spots in aircraft surveillance. In this paper, we applied a novel sensor fusion method with Interacting Multiple Model (IMM) filter to GBAS, ADS-B, MLAT, and WAM data in order to improve the reliability of the aircraft position. Results of performance analysis show that the position accuracy is improved by the proposed sensor fusion method with the IMM filter.

Research of maneuvering target prediction and tracking technology based on IMM algorithm

NASA Astrophysics Data System (ADS)

Cao, Zheng; Mao, Yao; Deng, Chao; Liu, Qiong; Chen, Jing

2016-09-01

Maneuvering target prediction and tracking technology is widely used in both military and civilian applications, the study of those technologies is all along the hotspot and difficulty. In the Electro-Optical acquisition-tracking-pointing system (ATP), the primary traditional maneuvering targets are ballistic target, large aircraft and other big targets. Those targets have the features of fast velocity and a strong regular trajectory and Kalman Filtering and polynomial fitting have good effects when they are used to track those targets. In recent years, the small unmanned aerial vehicles developed rapidly for they are small, nimble and simple operation. The small unmanned aerial vehicles have strong maneuverability in the observation system of ATP although they are close-in, slow and small targets. Moreover, those vehicles are under the manual operation, therefore, the acceleration of them changes greatly and they move erratically. So the prediction and tracking precision is low when traditional algorithms are used to track the maneuvering fly of those targets, such as speeding up, turning, climbing and so on. The interacting multiple model algorithm (IMM) use multiple models to match target real movement trajectory, there are interactions between each model. The IMM algorithm can switch model based on a Markov chain to adapt to the change of target movement trajectory, so it is suitable to solve the prediction and tracking problems of the small unmanned aerial vehicles because of the better adaptability of irregular movement. This paper has set up model set of constant velocity model (CV), constant acceleration model (CA), constant turning model (CT) and current statistical model. And the results of simulating and analyzing the real movement trajectory data of the small unmanned aerial vehicles show that the prediction and tracking technology based on the interacting multiple model algorithm can get relatively lower tracking error and improve tracking precision comparing with traditional algorithms.

The Integrated Medical Model: Statistical Forecasting of Risks to Crew Health and Mission Success

NASA Technical Reports Server (NTRS)

Fitts, M. A.; Kerstman, E.; Butler, D. J.; Walton, M. E.; Minard, C. G.; Saile, L. G.; Toy, S.; Myers, J.

2008-01-01

The Integrated Medical Model (IMM) helps capture and use organizational knowledge across the space medicine, training, operations, engineering, and research domains. The IMM uses this domain knowledge in the context of a mission and crew profile to forecast crew health and mission success risks. The IMM is most helpful in comparing the risk of two or more mission profiles, not as a tool for predicting absolute risk. The process of building the IMM adheres to Probability Risk Assessment (PRA) techniques described in NASA Procedural Requirement (NPR) 8705.5, and uses current evidence-based information to establish a defensible position for making decisions that help ensure crew health and mission success. The IMM quantitatively describes the following input parameters: 1) medical conditions and likelihood, 2) mission duration, 3) vehicle environment, 4) crew attributes (e.g. age, sex), 5) crew activities (e.g. EVA's, Lunar excursions), 6) diagnosis and treatment protocols (e.g. medical equipment, consumables pharmaceuticals), and 7) Crew Medical Officer (CMO) training effectiveness. It is worth reiterating that the IMM uses the data sets above as inputs. Many other risk management efforts stop at determining only likelihood. The IMM is unique in that it models not only likelihood, but risk mitigations, as well as subsequent clinical outcomes based on those mitigations. Once the mathematical relationships among the above parameters are established, the IMM uses a Monte Carlo simulation technique (a random sampling of the inputs as described by their statistical distribution) to determine the probable outcomes. Because the IMM is a stochastic model (i.e. the input parameters are represented by various statistical distributions depending on the data type), when the mission is simulated 10-50,000 times with a given set of medical capabilities (risk mitigations), a prediction of the most probable outcomes can be generated. For each mission, the IMM tracks which conditions occurred and decrements the pharmaceuticals and supplies required to diagnose and treat these medical conditions. If supplies are depleted, then the medical condition goes untreated, and crew and mission risk increase. The IMM currently models approximately 30 medical conditions. By the end of FY2008, the IMM will be modeling over 100 medical conditions, approximately 60 of which have been recorded to have occurred during short and long space missions.

Integrated Medical Model (IMM) 4.0 Enhanced Functionalities

NASA Technical Reports Server (NTRS)

Young, M.; Keenan, A. B.; Saile, L.; Boley, L. A.; Walton, M. E.; Shah, R. V.; Kerstman, E. L.; Myers, J. G.

2015-01-01

The Integrated Medical Model is a probabilistic simulation model that uses input data on 100 medical conditions to simulate expected medical events, the resources required to treat, and the resulting impact to the mission for specific crew and mission characteristics. The newest development version of IMM, IMM v4.0, adds capabilities that remove some of the conservative assumptions that underlie the current operational version, IMM v3. While IMM v3 provides the framework to simulate whether a medical event occurred, IMMv4 also simulates when the event occurred during a mission timeline. This allows for more accurate estimation of mission time lost and resource utilization. In addition to the mission timeline, IMMv4.0 features two enhancements that address IMM v3 assumptions regarding medical event treatment. Medical events in IMMv3 are assigned the untreated outcome if any resource required to treat the event was unavailable. IMMv4 allows for partially treated outcomes that are proportional to the amount of required resources available, thus removing the dichotomous treatment assumption. An additional capability IMMv4 is to use an alternative medical resource when the primary resource assigned to the condition is depleted, more accurately reflecting the real-world system. The additional capabilities defining IMM v4.0the mission timeline, partial treatment, and alternate drug result in more realistic predicted mission outcomes. The primary model outcomes of IMM v4.0 for the ISS6 mission, including mission time lost, probability of evacuation, and probability of loss of crew life, are be compared to those produced by the current operational version of IMM to showcase enhanced prediction capabilities.

Validation of the Integrated Medical Model Using Historical Space Flight Data

NASA Technical Reports Server (NTRS)

Kerstman, Eric L.; Minard, Charles G.; FreiredeCarvalho, Mary H.; Walton, Marlei E.; Myers, Jerry G., Jr.; Saile, Lynn G.; Lopez, Vilma; Butler, Douglas J.; Johnson-Throop, Kathy A.

2010-01-01

The Integrated Medical Model (IMM) utilizes Monte Carlo methodologies to predict the occurrence of medical events, utilization of resources, and clinical outcomes during space flight. Real-world data may be used to demonstrate the accuracy of the model. For this analysis, IMM predictions were compared to data from historical shuttle missions, not yet included as model source input. Initial goodness of fit test-ing on International Space Station data suggests that the IMM may overestimate the number of occurrences for three of the 83 medical conditions in the model. The IMM did not underestimate the occurrence of any medical condition. Initial comparisons with shuttle data demonstrate the importance of understanding crew preference (i.e., preferred analgesic) for accurately predicting the utilization of re-sources. The initial analysis demonstrates the validity of the IMM for its intended use and highlights areas for improvement.

Integrated Medical Model Project - Overview and Summary of Historical Application

NASA Technical Reports Server (NTRS)

Myers, J.; Boley, L.; Butler, D.; Foy, M.; Goodenow, D.; Griffin, D.; Keenan, A.; Kerstman, E.; Melton, S.; McGuire, K.;

IMM-H004, A New Coumarin Derivative, Improved Focal Cerebral Ischemia via Blood-Brain Barrier Protection in Rats.

PubMed

Niu, Fei; Song, Xiu-Yun; Hu, Jin-Feng; Zuo, Wei; Kong, Ling-Lei; Wang, Xiao-Feng; Han, Ning; Chen, Nai-Hong

2017-10-01

IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a novel coumarin derivative that showed better effect in improving global cerebral ischemia in rats. However, the effects and mechanisms in focal cerebral ischemia were not clear. Blood-brain barrier (BBB) protection is a vital strategy for the treatment of cerebral ischemia. This study is to investigate whether IMM-H004 improves brain ischemia injury via BBB protection. Focal brain ischemia model was induced by middle cerebral artery occlusion for 1 hour and reperfusion (MCAO/R) for 24 hours in rats. IMM-H004 (1.5, 3, 6 mg/kg) and edaravone (positive drug, 6 mg/kg) were administered after 5 minutes of occlusion. Neurological score and TTC staining were used to evaluate the effect of IMM-H004. Evans Blue (EB) staining and electron microscopy were used to assess BBB permeability. Western blot, reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect the expression of BBB structure-related proteins. Compared with the model group, IMM-H004 in the focal brain ischemia model improved neurological function and reduced cerebral infarction size and edema content. IMM-H004 sharply reduced the EB content and alleviated BBB structure. In addition, IMM-H004 increased the level of zonula occludens (ZO-1) and occluding, decreased the level of aquaporin 4 and matrix metalloproteinase 9, either in cortex or in hippocampus. And all of these changed were related to BBB protection. IMM-H004 improved cerebral ischemia injury via BBB protection. For a potential therapy drug of cerebral ischemia, IMM-H004 merits further study. Copyright © 2017. Published by Elsevier Inc.

Integrated Medical Model Overview

NASA Technical Reports Server (NTRS)

Myers, J.; Boley, L.; Foy, M.; Goodenow, D.; Griffin, D.; Keenan, A.; Kerstman, E.; Melton, S.; McGuire, K.; Saile, L.;

Estimated Probabililty of Chest Injury During an International Space Station Mission

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Milo, Eric A.; Brooker, John E.; Weaver, Aaron S.; Myers, Jerry G., Jr.

2013-01-01

The Integrated Medical Model (IMM) is a decision support tool that is useful to spaceflight mission planners and medical system designers when assessing risks and optimizing medical systems. The IMM project maintains a database of medical conditions that could occur during a spaceflight. The IMM project is in the process of assigning an incidence rate, the associated functional impairment, and a best and a worst case end state for each condition. The purpose of this work was to develop the IMM Chest Injury Module (CIM). The CIM calculates the incidence rate of chest injury per person-year of spaceflight on the International Space Station (ISS). The CIM was built so that the probability of chest injury during one year on ISS could be predicted. These results will be incorporated into the IMM Chest Injury Clinical Finding Form and used within the parent IMM model.

Estimated Probability of Traumatic Abdominal Injury During an International Space Station Mission

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Brooker, John E.; Weavr, Aaron S.; Myers, Jerry G., Jr.; McRae, Michael P.

2013-01-01

The Integrated Medical Model (IMM) is a decision support tool that is useful to spaceflight mission planners and medical system designers when assessing risks and optimizing medical systems. The IMM project maintains a database of medical conditions that could occur during a spaceflight. The IMM project is in the process of assigning an incidence rate, the associated functional impairment, and a best and a worst case end state for each condition. The purpose of this work was to develop the IMM Abdominal Injury Module (AIM). The AIM calculates an incidence rate of traumatic abdominal injury per person-year of spaceflight on the International Space Station (ISS). The AIM was built so that the probability of traumatic abdominal injury during one year on ISS could be predicted. This result will be incorporated into the IMM Abdominal Injury Clinical Finding Form and used within the parent IMM model.

An IMM-Aided ZUPT Methodology for an INS/DVL Integrated Navigation System.

PubMed

Yao, Yiqing; Xu, Xiaosu; Xu, Xiang

2017-09-05

Inertial navigation system (INS)/Doppler velocity log (DVL) integration is the most common navigation solution for underwater vehicles. Due to the complex underwater environment, the velocity information provided by DVL always contains some errors. To improve navigation accuracy, zero velocity update (ZUPT) technology is considered, which is an effective algorithm for land vehicles to mitigate the navigation error during the pure INS mode. However, in contrast to ground vehicles, the ZUPT solution cannot be used directly for underwater vehicles because of the existence of the water current. In order to leverage the strengths of the ZUPT method and the INS/DVL solution, an interactive multiple model (IMM)-aided ZUPT methodology for the INS/DVL-integrated underwater navigation system is proposed. Both the INS/DVL and INS/ZUPT models are constructed and operated in parallel, with weights calculated according to their innovations and innovation covariance matrices. Simulations are conducted to evaluate the proposed algorithm. The results indicate that the IMM-aided ZUPT solution outperforms both the INS/DVL solution and the INS/ZUPT solution in the underwater environment, which can properly distinguish between the ZUPT and non-ZUPT conditions. In addition, during DVL outage, the effectiveness of the proposed algorithm is also verified.

Implementation of a Parameterized Interacting Multiple Model Filter on an FPGA for Satellite Communications

NASA Technical Reports Server (NTRS)

Hackett, Timothy M.; Bilen, Sven G.; Ferreira, Paulo Victor R.; Wyglinski, Alexander M.; Reinhart, Richard C.

2016-01-01

In a communications channel, the space environment between a spacecraft and an Earth ground station can potentially cause the loss of a data link or at least degrade its performance due to atmospheric effects, shadowing, multipath, or other impairments. In adaptive and coded modulation, the signal power level at the receiver can be used in order to choose a modulation-coding technique that maximizes throughput while meeting bit error rate (BER) and other performance requirements. It is the goal of this research to implement a generalized interacting multiple model (IMM) filter based on Kalman filters for improved received power estimation on software-dened radio (SDR) technology for satellite communications applications. The IMM filter has been implemented in Verilog consisting of a customizable bank of Kalman filters for choosing between performance and resource utilization. Each Kalman filter can be implemented using either solely a Schur complement module (for high area efficiency) or with Schur complement, matrix multiplication, and matrix addition modules (for high performance). These modules were simulated and synthesized for the Virtex II platform on the JPL Radio Experimenter Development System (EDS) at NASA Glenn Research Center. The results for simulation, synthesis, and hardware testing are presented.

The Integrated Medical Model: A Risk Assessment and Decision Support Tool for Space Flight Medical Systems

NASA Technical Reports Server (NTRS)

Kerstman, Eric; Minard, Charles; Saile, Lynn; deCarvalho, Mary Freire; Myers, Jerry; Walton, Marlei; Butler, Douglas; Iyengar, Sriram; Johnson-Throop, Kathy; Baumann, David

2009-01-01

The Integrated Medical Model (IMM) is a decision support tool that is useful to mission planners and medical system designers in assessing risks and designing medical systems for space flight missions. The IMM provides an evidence based approach for optimizing medical resources and minimizing risks within space flight operational constraints. The mathematical relationships among mission and crew profiles, medical condition incidence data, in-flight medical resources, potential crew functional impairments, and clinical end-states are established to determine probable mission outcomes. Stochastic computational methods are used to forecast probability distributions of crew health and medical resource utilization, as well as estimates of medical evacuation and loss of crew life. The IMM has been used in support of the International Space Station (ISS) medical kit redesign, the medical component of the ISS Probabilistic Risk Assessment, and the development of the Constellation Medical Conditions List. The IMM also will be used to refine medical requirements for the Constellation program. The IMM outputs for ISS and Constellation design reference missions will be presented to demonstrate the potential of the IMM in assessing risks, planning missions, and designing medical systems. The implementation of the IMM verification and validation plan will be reviewed. Additional planned capabilities of the IMM, including optimization techniques and the inclusion of a mission timeline, will be discussed. Given the space flight constraints of mass, volume, and crew medical training, the IMM is a valuable risk assessment and decision support tool for medical system design and mission planning.

Intelligence-aided multitarget tracking for urban operations - a case study: counter terrorism

NASA Astrophysics Data System (ADS)

Sathyan, T.; Bharadwaj, K.; Sinha, A.; Kirubarajan, T.

2006-05-01

In this paper, we present a framework for tracking multiple mobile targets in an urban environment based on data from multiple sources of information, and for evaluating the threat these targets pose to assets of interest (AOI). The motivating scenario is one where we have to track many targets, each with different (unknown) destinations and/or intents. The tracking algorithm is aided by information about the urban environment (e.g., road maps, buildings, hideouts), and strategic and intelligence data. The tracking algorithm needs to be dynamic in that it has to handle a time-varying number of targets and the ever-changing urban environment depending on the locations of the moving objects and AOI. Our solution uses the variable structure interacting multiple model (VS-IMM) estimator, which has been shown to be effective in tracking targets based on road map information. Intelligence information is represented as target class information and incorporated through a combined likelihood calculation within the VS-IMM estimator. In addition, we develop a model to calculate the probability that a particular target can attack a given AOI. This model for the calculation of the probability of attack is based on the target kinematic and class information. Simulation results are presented to demonstrate the operation of the proposed framework on a representative scenario.

The Integrated Medical Model: Outcomes from Independent Review

NASA Technical Reports Server (NTRS)

Myers, J.; Garcia, Y.; Griffin, D.; Arellano, J.; Boley, L.; Goodenow, D. A.; Kerstman, E.; Reyes, D.; Saile, L.; Walton, M.;

The Integrated Medical Model: A Risk Assessment and Decision Support Tool for Human Space Flight Missions

NASA Technical Reports Server (NTRS)

Kerstman, Eric L.; Minard, Charles; FreiredeCarvalho, Mary H.; Walton, Marlei E.; Myers, Jerry G., Jr.; Saile, Lynn G.; Lopez, Vilma; Butler, Douglas J.; Johnson-Throop, Kathy A.

2011-01-01

This slide presentation reviews the Integrated Medical Model (IMM) and its use as a risk assessment and decision support tool for human space flight missions. The IMM is an integrated, quantified, evidence-based decision support tool useful to NASA crew health and mission planners. It is intended to assist in optimizing crew health, safety and mission success within the constraints of the space flight environment for in-flight operations. It uses ISS data to assist in planning for the Exploration Program and it is not intended to assist in post flight research. The IMM was used to update Probability Risk Assessment (PRA) for the purpose of updating forecasts for the conditions requiring evacuation (EVAC) or Loss of Crew Life (LOC) for the ISS. The IMM validation approach includes comparison with actual events and involves both qualitative and quantitaive approaches. The results of these comparisons are reviewed. Another use of the IMM is to optimize the medical kits taking into consideration the specific mission and the crew profile. An example of the use of the IMM to optimize the medical kits is reviewed.

An IMM-Aided ZUPT Methodology for an INS/DVL Integrated Navigation System

PubMed Central

Yao, Yiqing

2017-01-01

Inertial navigation system (INS)/Doppler velocity log (DVL) integration is the most common navigation solution for underwater vehicles. Due to the complex underwater environment, the velocity information provided by DVL always contains some errors. To improve navigation accuracy, zero velocity update (ZUPT) technology is considered, which is an effective algorithm for land vehicles to mitigate the navigation error during the pure INS mode. However, in contrast to ground vehicles, the ZUPT solution cannot be used directly for underwater vehicles because of the existence of the water current. In order to leverage the strengths of the ZUPT method and the INS/DVL solution, an interactive multiple model (IMM)-aided ZUPT methodology for the INS/DVL-integrated underwater navigation system is proposed. Both the INS/DVL and INS/ZUPT models are constructed and operated in parallel, with weights calculated according to their innovations and innovation covariance matrices. Simulations are conducted to evaluate the proposed algorithm. The results indicate that the IMM-aided ZUPT solution outperforms both the INS/DVL solution and the INS/ZUPT solution in the underwater environment, which can properly distinguish between the ZUPT and non-ZUPT conditions. In addition, during DVL outage, the effectiveness of the proposed algorithm is also verified. PMID:28872602

Infrared measurement and composite tracking algorithm for air-breathing hypersonic vehicles

NASA Astrophysics Data System (ADS)

Zhang, Zhao; Gao, Changsheng; Jing, Wuxing

2018-03-01

Air-breathing hypersonic vehicles have capabilities of hypersonic speed and strong maneuvering, and thus pose a significant challenge to conventional tracking methodologies. To achieve desirable tracking performance for hypersonic targets, this paper investigates the problems related to measurement model design and tracking model mismatching. First, owing to the severe aerothermal effect of hypersonic motion, an infrared measurement model in near space is designed and analyzed based on target infrared radiation and an atmospheric model. Second, using information from infrared sensors, a composite tracking algorithm is proposed via a combination of the interactive multiple models (IMM) algorithm, fitting dynamics model, and strong tracking filter. During the procedure, the IMMs algorithm generates tracking data to establish a fitting dynamics model of the target. Then, the strong tracking unscented Kalman filter is employed to estimate the target states for suppressing the impact of target maneuvers. Simulations are performed to verify the feasibility of the presented composite tracking algorithm. The results demonstrate that the designed infrared measurement model effectively and continuously observes hypersonic vehicles, and the proposed composite tracking algorithm accurately and stably tracks these targets.

Measuring motivational characteristics of courses: applying Keller's instructional materials motivation survey to a web-based course.

PubMed

Cook, David A; Beckman, Thomas J; Thomas, Kris G; Thompson, Warren G

2009-11-01

The Instructional Materials Motivation Survey (IMMS) purports to assess the motivational characteristics of instructional materials or courses using the Attention, Relevance, Confidence, and Satisfaction (ARCS) model of motivation. The IMMS has received little use or study in medical education. The authors sought to evaluate the validity of IMMS scores and compare scores between standard and adaptive Web-based learning modules. During the 2005-2006 academic year, 124 internal medicine residents at the Mayo School of Graduate Medical Education (Rochester, Minnesota) were asked to complete the IMMS for two Web-based learning modules. Participants were randomly assigned to use one module that adapted to their prior knowledge of the topic, and one module using a nonadaptive design. IMMS internal structure was evaluated using Cronbach alpha and interdimension score correlations. Relations to other variables were explored through correlation with global module satisfaction and regression with knowledge scores. Of the 124 eligible participants, 79 (64%) completed the IMMS at least once. Cronbach alpha was >or=0.75 for scores from all IMMS dimensions. Interdimension score correlations ranged 0.40 to 0.80, whereas correlations between IMMS scores and global satisfaction ratings ranged 0.40 to 0.63 (P<.001). Knowledge scores were associated with Attention and Relevance subscores (P=.033 and .01, respectively) but not with other IMMS dimensions (P>or=.07). IMMS scores were similar between module designs (on a five-point scale, differences ranged from 0.0 to 0.15, P>or=.33). These limited data generally support the validity of IMMS scores. Adaptive and standard Web-based instructional designs were similarly motivating. Cautious use and further study of the IMMS are warranted.

Integrated Modeling, Mapping, and Simulation (IMMS) framework for planning exercises.

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

Friedman-Hill, Ernest J.; Plantenga, Todd D.

2010-06-01

The Integrated Modeling, Mapping, and Simulation (IMMS) program is designing and prototyping a simulation and collaboration environment for linking together existing and future modeling and simulation tools to enable analysts, emergency planners, and incident managers to more effectively, economically, and rapidly prepare, analyze, train, and respond to real or potential incidents. When complete, the IMMS program will demonstrate an integrated modeling and simulation capability that supports emergency managers and responders with (1) conducting 'what-if' analyses and exercises to address preparedness, analysis, training, operations, and lessons learned, and (2) effectively, economically, and rapidly verifying response tactics, plans and procedures.

Sensitivity Analysis of the Integrated Medical Model for ISS Programs

NASA Technical Reports Server (NTRS)

Goodenow, D. A.; Myers, J. G.; Arellano, J.; Boley, L.; Garcia, Y.; Saile, L.; Walton, M.; Kerstman, E.; Reyes, D.; Young, M.

2016-01-01

Sensitivity analysis estimates the relative contribution of the uncertainty in input values to the uncertainty of model outputs. Partial Rank Correlation Coefficient (PRCC) and Standardized Rank Regression Coefficient (SRRC) are methods of conducting sensitivity analysis on nonlinear simulation models like the Integrated Medical Model (IMM). The PRCC method estimates the sensitivity using partial correlation of the ranks of the generated input values to each generated output value. The partial part is so named because adjustments are made for the linear effects of all the other input values in the calculation of correlation between a particular input and each output. In SRRC, standardized regression-based coefficients measure the sensitivity of each input, adjusted for all the other inputs, on each output. Because the relative ranking of each of the inputs and outputs is used, as opposed to the values themselves, both methods accommodate the nonlinear relationship of the underlying model. As part of the IMM v4.0 validation study, simulations are available that predict 33 person-missions on ISS and 111 person-missions on STS. These simulated data predictions feed the sensitivity analysis procedures. The inputs to the sensitivity procedures include the number occurrences of each of the one hundred IMM medical conditions generated over the simulations and the associated IMM outputs: total quality time lost (QTL), number of evacuations (EVAC), and number of loss of crew lives (LOCL). The IMM team will report the results of using PRCC and SRRC on IMM v4.0 predictions of the ISS and STS missions created as part of the external validation study. Tornado plots will assist in the visualization of the condition-related input sensitivities to each of the main outcomes. The outcomes of this sensitivity analysis will drive review focus by identifying conditions where changes in uncertainty could drive changes in overall model output uncertainty. These efforts are an integral part of the overall verification, validation, and credibility review of IMM v4.0.

In-Source Reduction of Disulfide-Bonded Peptides Monitored by Ion Mobility Mass Spectrometry

NASA Astrophysics Data System (ADS)

Stocks, Bradley B.; Melanson, Jeremy E.

2018-02-01

Many peptides with antimicrobial activity and/or therapeutic potential contain disulfide bonds as a means to enhance stability, and their quantitation is often performed using electrospray ionization mass spectrometry (ESI-MS). Disulfides can be reduced during ESI under commonly used instrument conditions, which has the potential to hinder accurate peptide quantitation. We demonstrate that this in-source reduction (ISR) is predominantly observed for peptides infused from acidic solutions and subjected to elevated ESI voltages (3-4 kV). ISR is readily apparent in the mass spectrum of oxytocin—a small, single disulfide-containing peptide. However, subtle m/z shifts due to partial ISR of highly charged (z ≥ 3) peptides with multiple disulfide linkages may proceed unnoticed. Ion mobility (IM)-MS separates ions on the basis of charge and shape in the gas phase, and using insulin as a model system, we show that IM-MS arrival time distributions (ATDs) are particularly sensitive to partial ISR of large peptides. Isotope modeling allows for the relative quantitation of disulfide-intact and partially reduced states of the mobility-separated peptide conformers. Interestingly, hepcidin peptides ionized from acidic solutions at elevated ESI voltages undergo gas-phase compaction, ostensibly due to partial disulfide ISR. Our IM-MS results lead us to propose that residual acid is the likely cause of disparate ATDs recently measured for hepcidin from different suppliers [Anal. Bioanal. Chem. 409, 2559-2567 (2017)]. Overall, our results demonstrate the utility of IM-MS to detect partial ISR of disulfide-bonded peptides and reinforce the notion that peptide/protein measurements should be carried out using minimally activating instrument conditions. [Figure not available: see fulltext.

Constrained State Estimation for Individual Localization in Wireless Body Sensor Networks

PubMed Central

Feng, Xiaoxue; Snoussi, Hichem; Liang, Yan; Jiao, Lianmeng

2014-01-01

Wireless body sensor networks based on ultra-wideband radio have recently received much research attention due to its wide applications in health-care, security, sports and entertainment. Accurate localization is a fundamental problem to realize the development of effective location-aware applications above. In this paper the problem of constrained state estimation for individual localization in wireless body sensor networks is addressed. Priori knowledge about geometry among the on-body nodes as additional constraint is incorporated into the traditional filtering system. The analytical expression of state estimation with linear constraint to exploit the additional information is derived. Furthermore, for nonlinear constraint, first-order and second-order linearizations via Taylor series expansion are proposed to transform the nonlinear constraint to the linear case. Examples between the first-order and second-order nonlinear constrained filters based on interacting multiple model extended kalman filter (IMM-EKF) show that the second-order solution for higher order nonlinearity as present in this paper outperforms the first-order solution, and constrained IMM-EKF obtains superior estimation than IMM-EKF without constraint. Another brownian motion individual localization example also illustrates the effectiveness of constrained nonlinear iterative least square (NILS), which gets better filtering performance than NILS without constraint. PMID:25390408

Multi-Sensor Fusion with Interaction Multiple Model and Chi-Square Test Tolerant Filter.

PubMed

Yang, Chun; Mohammadi, Arash; Chen, Qing-Wei

2016-11-02

Motivated by the key importance of multi-sensor information fusion algorithms in the state-of-the-art integrated navigation systems due to recent advancements in sensor technologies, telecommunication, and navigation systems, the paper proposes an improved and innovative fault-tolerant fusion framework. An integrated navigation system is considered consisting of four sensory sub-systems, i.e., Strap-down Inertial Navigation System (SINS), Global Navigation System (GPS), the Bei-Dou2 (BD2) and Celestial Navigation System (CNS) navigation sensors. In such multi-sensor applications, on the one hand, the design of an efficient fusion methodology is extremely constrained specially when no information regarding the system's error characteristics is available. On the other hand, the development of an accurate fault detection and integrity monitoring solution is both challenging and critical. The paper addresses the sensitivity issues of conventional fault detection solutions and the unavailability of a precisely known system model by jointly designing fault detection and information fusion algorithms. In particular, by using ideas from Interacting Multiple Model (IMM) filters, the uncertainty of the system will be adjusted adaptively by model probabilities and using the proposed fuzzy-based fusion framework. The paper also addresses the problem of using corrupted measurements for fault detection purposes by designing a two state propagator chi-square test jointly with the fusion algorithm. Two IMM predictors, running in parallel, are used and alternatively reactivated based on the received information form the fusion filter to increase the reliability and accuracy of the proposed detection solution. With the combination of the IMM and the proposed fusion method, we increase the failure sensitivity of the detection system and, thereby, significantly increase the overall reliability and accuracy of the integrated navigation system. Simulation results indicate that the proposed fault tolerant fusion framework provides superior performance over its traditional counterparts.

Multi-Sensor Fusion with Interaction Multiple Model and Chi-Square Test Tolerant Filter

PubMed Central

Yang, Chun; Mohammadi, Arash; Chen, Qing-Wei

2016-01-01

Motivated by the key importance of multi-sensor information fusion algorithms in the state-of-the-art integrated navigation systems due to recent advancements in sensor technologies, telecommunication, and navigation systems, the paper proposes an improved and innovative fault-tolerant fusion framework. An integrated navigation system is considered consisting of four sensory sub-systems, i.e., Strap-down Inertial Navigation System (SINS), Global Navigation System (GPS), the Bei-Dou2 (BD2) and Celestial Navigation System (CNS) navigation sensors. In such multi-sensor applications, on the one hand, the design of an efficient fusion methodology is extremely constrained specially when no information regarding the system’s error characteristics is available. On the other hand, the development of an accurate fault detection and integrity monitoring solution is both challenging and critical. The paper addresses the sensitivity issues of conventional fault detection solutions and the unavailability of a precisely known system model by jointly designing fault detection and information fusion algorithms. In particular, by using ideas from Interacting Multiple Model (IMM) filters, the uncertainty of the system will be adjusted adaptively by model probabilities and using the proposed fuzzy-based fusion framework. The paper also addresses the problem of using corrupted measurements for fault detection purposes by designing a two state propagator chi-square test jointly with the fusion algorithm. Two IMM predictors, running in parallel, are used and alternatively reactivated based on the received information form the fusion filter to increase the reliability and accuracy of the proposed detection solution. With the combination of the IMM and the proposed fusion method, we increase the failure sensitivity of the detection system and, thereby, significantly increase the overall reliability and accuracy of the integrated navigation system. Simulation results indicate that the proposed fault tolerant fusion framework provides superior performance over its traditional counterparts. PMID:27827832

Beating Heart Motion Accurate Prediction Method Based on Interactive Multiple Model: An Information Fusion Approach

PubMed Central

Xie, Weihong; Yu, Yang

2017-01-01

Robot-assisted motion compensated beating heart surgery has the advantage over the conventional Coronary Artery Bypass Graft (CABG) in terms of reduced trauma to the surrounding structures that leads to shortened recovery time. The severe nonlinear and diverse nature of irregular heart rhythm causes enormous difficulty for the robot to realize the clinic requirements, especially under arrhythmias. In this paper, we propose a fusion prediction framework based on Interactive Multiple Model (IMM) estimator, allowing each model to cover a distinguishing feature of the heart motion in underlying dynamics. We find that, at normal state, the nonlinearity of the heart motion with slow time-variant changing dominates the beating process. When an arrhythmia occurs, the irregularity mode, the fast uncertainties with random patterns become the leading factor of the heart motion. We deal with prediction problem in the case of arrhythmias by estimating the state with two behavior modes which can adaptively “switch” from one to the other. Also, we employed the signal quality index to adaptively determine the switch transition probability in the framework of IMM. We conduct comparative experiments to evaluate the proposed approach with four distinguished datasets. The test results indicate that the new proposed approach reduces prediction errors significantly. PMID:29124062

Beating Heart Motion Accurate Prediction Method Based on Interactive Multiple Model: An Information Fusion Approach.

PubMed

Liang, Fan; Xie, Weihong; Yu, Yang

2017-01-01

Robot-assisted motion compensated beating heart surgery has the advantage over the conventional Coronary Artery Bypass Graft (CABG) in terms of reduced trauma to the surrounding structures that leads to shortened recovery time. The severe nonlinear and diverse nature of irregular heart rhythm causes enormous difficulty for the robot to realize the clinic requirements, especially under arrhythmias. In this paper, we propose a fusion prediction framework based on Interactive Multiple Model (IMM) estimator, allowing each model to cover a distinguishing feature of the heart motion in underlying dynamics. We find that, at normal state, the nonlinearity of the heart motion with slow time-variant changing dominates the beating process. When an arrhythmia occurs, the irregularity mode, the fast uncertainties with random patterns become the leading factor of the heart motion. We deal with prediction problem in the case of arrhythmias by estimating the state with two behavior modes which can adaptively "switch" from one to the other. Also, we employed the signal quality index to adaptively determine the switch transition probability in the framework of IMM. We conduct comparative experiments to evaluate the proposed approach with four distinguished datasets. The test results indicate that the new proposed approach reduces prediction errors significantly.

A missense mutation in MYH1 is associated with susceptibility to immune-mediated myositis in Quarter Horses.

PubMed

Finno, Carrie J; Gianino, Giuliana; Perumbakkam, Sudeep; Williams, Zoë J; Bordbari, Matthew H; Gardner, Keri L; Burns, Erin; Peng, Sichong; Durward-Akhurst, Sian A; Valberg, Stephanie J

2018-03-06

The cause of immune-mediated myositis (IMM), characterized by recurrent, rapid-onset muscle atrophy in Quarter Horses (QH), is unknown. The histopathologic hallmark of IMM is lymphocytic infiltration of myofibers. The purpose of this study was to identify putative functional variants associated with equine IMM. A genome-wide association (GWA) study was performed on 36 IMM QHs and 54 breed matched unaffected QHs from the same environment using the Equine SNP50 and SNP70 genotyping arrays. A mixed model analysis identified nine SNPs within a ~ 2.87 Mb region on chr11 that were significantly (P unadjusted  < 1.4 × 10 - 6 ) associated with the IMM phenotype. Associated haplotypes within this region encompassed 38 annotated genes, including four myosin genes (MYH1, MYH2, MYH3, and MYH13). Whole genome sequencing of four IMM and four unaffected QHs identified a single segregating nonsynonymous E321G mutation in MYH1 encoding myosin heavy chain 2X. Genotyping of additional 35 IMM and 22 unaffected QHs confirmed an association (P = 2.9 × 10 - 5 ), and the putative mutation was absent in 175 horses from 21 non-QH breeds. Lymphocytic infiltrates occurred in type 2X myofibers and the proportion of 2X fibers was decreased in the presence of inflammation. Protein modeling and contact/stability analysis identified 14 residues affected by the mutation which significantly decreased stability. We conclude that a mutation in MYH1 is highly associated with susceptibility to the IMM phenotype in QH-related breeds. This is the first report of a mutation in MYH1 and the first link between a skeletal muscle myosin mutation and autoimmune disease.

Beneficial metabolic effects of 2', 3', 5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine in multiple biological matrices and intestinal flora of hyperlipidemic hamsters.

PubMed

Li, Tianqi; Sun, Shanshan; Zhang, Jinyue; Qu, Kai; Yang, Liu; Ma, Changlu; Jin, Xiangju; Zhu, Haibo; Wang, Yinghong

2018-06-21

ABSTRACT：Hyperlipidemia is one of the main causes of obesity, type 2 diabetes mellitus (T2DM) and atherosclerosis. The adenosine derivative, 2', 3', 5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) is an effective lipid-lowering compound that has important implications for the development of lipid-lowering drugs. Metabolomic analysis based on 1H-NMR was used to monitor dynamic changes in diverse biological media including serum, liver, urine, and feces in response to high-fat diet (HFD) and IMM-H007 treatments. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography (GC) analyses were performed to quantify the bile acids and fatty acids in the liver and feces. Fecal microbiome profiling was performed using Illumina sequencing of the 16S ribosomal RNA (16S rRNA) gene. IMM-H007 improved the metabolism of carbohydrate, ketone bodies, fatty acids, amino acids and bile acids in hyperlipidemic hamsters. The correlation between metabolite changes was explored in different biological media. Significant changes in gut microbiota were observed in the HFD and IMM-H007 treatment groups. In the HFD group at the phylum level, we found high levels of the Firmicutes genus and low levels of Bacteroidetes. In contrast, the administration of IMM-H007 reversed the levels of Firmicutes and Bacteroidetes. This reversal suggested that IMM-H007 may have the ability to regulate the composition of the gut flora. We also analyzed the correlation between the gut flora and the metabolites. Our results indicate that IMM-H007 treatment improves the hyperlipidemic metabolism and the structure of the gut microbiota in hyperlipidemic hamsters.

The Integrated Medical Model

NASA Technical Reports Server (NTRS)

Butler, Douglas J.; Kerstman, Eric

2010-01-01

This slide presentation reviews the goals and approach for the Integrated Medical Model (IMM). The IMM is a software decision support tool that forecasts medical events during spaceflight and optimizes medical systems during simulations. It includes information on the software capabilities, program stakeholders, use history, and the software logic.

Economic consequence of local control with radiotherapy: Cost analysis of internal mammary and medial supraclavicular lymph node radiotherapy in breast cancer

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

Lievens, Yolande; Kesteloot, Katrien; Bogaert, Walter van den

2005-11-15

Purpose: To investigate the financial implications of radiotherapy (RT) to the internal mammary and medial supraclavicular lymph node chain (IM-MS) in postoperative breast cancer. Methods and Materials: A cost-effectiveness and cost-utility analysis were performed, using Markov models, comparing the early and delayed costs and effects of IM-MS during a 20-year time span from a societal viewpoint. The outcome estimates were based on Level I evidence from postoperative RT literature and the cost estimates on the standard practice of the Leuven University Hospitals, with the RT costs derived from an activity-based costing program developed in the department. Results: On the basismore » of the assumptions of the model and seen during a 20-year time span, primary treatment including IM-MS RT results in a cost savings (approximately EURO 10,000) compared with a strategy without RT. Because IM-MS RT also results in better clinical effectiveness and greater quality of life, the treatment with IM-MS dominates the approach without IM-MS. Sensitivity analyses confirmed the robustness of these results in all tested circumstances. Although threshold values were found for the cost of IM-MS, the cost at relapse, and the quality of life after treatment, these were substantially different from the baseline estimates, indicating that it is very unlikely that omitting IM-MS would become superior. Conclusion: This ex-ante cost evaluation of IM-MS RT showed that the upfront costs of locoregional RT are easily compensated for by avoiding the costs of treating locoregional and distant relapse at a later stage. The cost-sparing effect of RT should, however, be evaluated for a sufficiently long time span and is most specifically found in tumors with a rather slow natural history and a multitude of available systemic treatments at relapse, such as breast cancer.« less

A longitudinal study of factors associated with acute and chronic mastitis and their impact on lamb growth rate in 10 suckler sheep flocks in Great Britain.

PubMed

Grant, Claire; Smith, Edward Mark; Green, Laura Elizabeth

2016-05-01

A 2-year prospective, longitudinal study of 10 suckler sheep flocks in Great Britain was run to identify factors associated with acute mastitis (AM) and chronic mastitis, and their impact on lamb growth rate. Data were collected on AM, intramammary masses (IMM; a marker for chronic mastitis), udder and teat conformation, teat lesions, body condition, ewe nutrition, litter size, lamb weight and general flock management. Each flock was visited twice each year, approximately 4 weeks before lambing and 9 weeks into lactation, for two years and all ewes present at a visit were examined. There were 7021 examinations in total. AM was reported in 2.1-3.0% of ewes/year; this ranged from 0.0% to 37.1% by flock. IMM were detected in 4.7% of ewes in pregnancy and 10.9% of ewes in lactation. Once an IMM had been detected there was an increased risk of future IMM although IMM were not consistently present. The majority of ewes had good udder conformation to suckle lambs. Factors associated with AM, IMM in pregnant and lactating ewes, udder conformation and lamb daily live weight gain were explored using mixed effect multivariable models. An increased risk of AM was associated with underfeeding protein in pregnancy (OR 4.05), forward pointing teats (OR 2.54), downward pointing teats (OR 4.68), rearing≥2 lambs (OR 2.65), non-traumatic teat lesions (OR 2.09); and marginally associated with the presence of IMM. An increased risk of IMM in lactation was associated with AM during lactation (OR 12.39), IMM in pregnancy (OR 4.79), IMM in the previous lactation (OR 4.77), underfeeding energy in pregnancy (OR 6.66) and traumatic teat lesions (OR 2.48). An increased risk of IMM in pregnancy was associated with IMM in the previous pregnancy, IMM in the previous lactation and underfeeding energy in the previous lactation (OR 2.95). Lower lamb daily live weight gain was associated with traumatic teat lesions, IMM in lactation (-0.01kg/day) and AM (-0.04kg/day). We conclude that inadequate nutrition is an important cause of mastitis in suckler ewes which farmers could address in part using current nutritional guidelines but further work is needed. The relationship between AM and IMM indicates that separating or culling ewes with IMM would help reduce AM. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiple Gas-Phase Conformations of a Synthetic Linear Poly(acrylamide) Polymer Observed Using Ion Mobility-Mass Spectrometry.

PubMed

Haler, Jean R N; Far, Johann; Aqil, Abdelhafid; Claereboudt, Jan; Tomczyk, Nick; Giles, Kevin; Jérôme, Christine; De Pauw, Edwin

2017-11-01

Ion mobility-mass spectrometry (IM-MS) has emerged as a powerful separation and identification tool to characterize synthetic polymer mixtures and topologies (linear, cyclic, star-shaped,…). Electrospray coupled to IM-MS already revealed the coexistence of several charge state-dependent conformations for a single charge state of biomolecules with strong intramolecular interactions, even when limited resolving power IM-MS instruments were used. For synthetic polymers, the sample's polydispersity allows the observation of several chain lengths. A unique collision cross-section (CCS) trend is usually observed when increasing the degree of polymerization (DP) at constant charge state, allowing the deciphering of different polymer topologies. In this paper, we report multiple coexisting CCS trends when increasing the DP at constant charge state for linear poly(acrylamide) PAAm in the gas phase. This is similar to observations on peptides and proteins. Biomolecules show in addition population changes when collisionally heating the ions. In the case of synthetic PAAm, fragmentation occurred before reaching the energy for conformation conversion. These observations, which were made on two different IM-MS instruments (SYNAPT G2 HDMS and high resolution multi-pass cyclic T-Wave prototype from Waters), limit the use of ion mobility for synthetic polymer topology interpretations to polymers where unique CCS values are observed for each DP at constant charge state. Graphical Abstract ᅟ.

Multiple Gas-Phase Conformations of a Synthetic Linear Poly(acrylamide) Polymer Observed Using Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Haler, Jean R. N.; Far, Johann; Aqil, Abdelhafid; Claereboudt, Jan; Tomczyk, Nick; Giles, Kevin; Jérôme, Christine; De Pauw, Edwin

2017-08-01

Ion mobility-mass spectrometry (IM-MS) has emerged as a powerful separation and identification tool to characterize synthetic polymer mixtures and topologies (linear, cyclic, star-shaped,…). Electrospray coupled to IM-MS already revealed the coexistence of several charge state-dependent conformations for a single charge state of biomolecules with strong intramolecular interactions, even when limited resolving power IM-MS instruments were used. For synthetic polymers, the sample's polydispersity allows the observation of several chain lengths. A unique collision cross-section (CCS) trend is usually observed when increasing the degree of polymerization (DP) at constant charge state, allowing the deciphering of different polymer topologies. In this paper, we report multiple coexisting CCS trends when increasing the DP at constant charge state for linear poly(acrylamide) PAAm in the gas phase. This is similar to observations on peptides and proteins. Biomolecules show in addition population changes when collisionally heating the ions. In the case of synthetic PAAm, fragmentation occurred before reaching the energy for conformation conversion. These observations, which were made on two different IM-MS instruments (SYNAPT G2 HDMS and high resolution multi-pass cyclic T-Wave prototype from Waters), limit the use of ion mobility for synthetic polymer topology interpretations to polymers where unique CCS values are observed for each DP at constant charge state. [Figure not available: see fulltext.

Adaptive Estimation and Heuristic Optimization of Nonlinear Spacecraft Attitude Dynamics

DTIC Science & Technology

2016-09-15

Algorithm GPS Global Positioning System HOUF Higher Order Unscented Filter IC initial conditions IMM Interacting Multiple Model IMU Inertial Measurement Unit ...sources ranging from inertial measurement units to star sensors are used to construct observations for attitude estimation algorithms. The sensor...parameters. A single vector measurement will provide two independent parameters, as a unit vector constraint removes a DOF making the problem underdetermined

Integration of Evidence Base into a Probabilistic Risk Assessment

NASA Technical Reports Server (NTRS)

Saile, Lyn; Lopez, Vilma; Bickham, Grandin; Kerstman, Eric; FreiredeCarvalho, Mary; Byrne, Vicky; Butler, Douglas; Myers, Jerry; Walton, Marlei

2011-01-01

INTRODUCTION: A probabilistic decision support model such as the Integrated Medical Model (IMM) utilizes an immense amount of input data that necessitates a systematic, integrated approach for data collection, and management. As a result of this approach, IMM is able to forecasts medical events, resource utilization and crew health during space flight. METHODS: Inflight data is the most desirable input for the Integrated Medical Model. Non-attributable inflight data is collected from the Lifetime Surveillance for Astronaut Health study as well as the engineers, flight surgeons, and astronauts themselves. When inflight data is unavailable cohort studies, other models and Bayesian analyses are used, in addition to subject matters experts input on occasion. To determine the quality of evidence of a medical condition, the data source is categorized and assigned a level of evidence from 1-5; the highest level is one. The collected data reside and are managed in a relational SQL database with a web-based interface for data entry and review. The database is also capable of interfacing with outside applications which expands capabilities within the database itself. Via the public interface, customers can access a formatted Clinical Findings Form (CLiFF) that outlines the model input and evidence base for each medical condition. Changes to the database are tracked using a documented Configuration Management process. DISSCUSSION: This strategic approach provides a comprehensive data management plan for IMM. The IMM Database s structure and architecture has proven to support additional usages. As seen by the resources utilization across medical conditions analysis. In addition, the IMM Database s web-based interface provides a user-friendly format for customers to browse and download the clinical information for medical conditions. It is this type of functionality that will provide Exploratory Medicine Capabilities the evidence base for their medical condition list. CONCLUSION: The IMM Database in junction with the IMM is helping NASA aerospace program improve the health care and reduce risk for the astronauts crew. Both the database and model will continue to expand to meet customer needs through its multi-disciplinary evidence based approach to managing data. Future expansion could serve as a platform for a Space Medicine Wiki of medical conditions.

Analyzing slowly exchanging protein conformations by ion mobility mass spectrometry: study of the dynamic equilibrium of prolyl oligopeptidase.

PubMed

López, Abraham; Vilaseca, Marta; Madurga, Sergio; Varese, Monica; Tarragó, Teresa; Giralt, Ernest

2016-07-01

Ion mobility mass spectrometry (IMMS) is a biophysical technique that allows the separation of isobaric species on the basis of their size and shape. The high separation capacity, sensitivity and relatively fast time scale measurements confer IMMS great potential for the study of proteins in slow (µs-ms) conformational equilibrium in solution. However, the use of this technique for examining dynamic proteins is still not generalized. One of the major limitations is the instability of protein ions in the gas phase, which raises the question as to what extent the structures detected reflect those in solution. Here, we addressed this issue by analyzing the conformational landscape of prolyl oligopeptidase (POP) - a model of a large dynamic enzyme in the µs-ms range - by native IMMS and compared the results obtained in the gas phase with those obtained in solution. In order to interpret the experimental results, we used theoretical simulations. In addition, the stability of POP gaseous ions was explored by charge reduction and collision-induced unfolding experiments. Our experiments disclosed two species of POP in the gas phase, which correlated well with the open and closed conformations in equilibrium in solution; moreover, a gas-phase collapsed form of POP was also detected. Therefore, our findings not only support the potential of IMMS for the study of multiple co-existing conformations of large proteins in slow dynamic equilibrium in solution but also stress the need for careful data analysis to avoid artifacts. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Integrated Medical Model - A Risk Assessment and Decision Support Tool for Human Space Flight Missions

NASA Technical Reports Server (NTRS)

Kerstman, Eric; Minard, Charles G.; Saile, Lynn; FreiredeCarvalho, Mary; Myers, Jerry; Walton, Marlei; Butler, Douglas; Lopez, Vilma

2010-01-01

The Integrated Medical Model (IMM) is a decision support tool that is useful to space flight mission planners and medical system designers in assessing risks and optimizing medical systems. The IMM employs an evidence-based, probabilistic risk assessment (PRA) approach within the operational constraints of space flight.

IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet.

PubMed

Shi, Huijie; Wang, Qingchun; Yang, Liu; Xie, Shouxia; Zhu, Haibo

2017-09-01

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2',3',5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) can eliminate hepatic steatosis in hamsters fed a high-fat diet (HFD), as a model of NAFLD. Compared with HFD-only controls, IMM-H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1 H-MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM-H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM-H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo , IMM-H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. Thus, IMM-H007 has therapeutic potential for NAFLD.

The Use of the Integrated Medical Model for Forecasting and Mitigating Medical Risks for a Near-Earth Asteroid Mission

NASA Technical Reports Server (NTRS)

Kerstman, Eric; Saile, Lynn; Freire de Carvalho, Mary; Myers, Jerry; Walton, Marlei; Butler, Douglas; Lopez, Vilma

2011-01-01

Introduction The Integrated Medical Model (IMM) is a decision support tool that is useful to space flight mission managers and medical system designers in assessing risks and optimizing medical systems. The IMM employs an evidence-based, probabilistic risk assessment (PRA) approach within the operational constraints of space flight. Methods Stochastic computational methods are used to forecast probability distributions of medical events, crew health metrics, medical resource utilization, and probability estimates of medical evacuation and loss of crew life. The IMM can also optimize medical kits within the constraints of mass and volume for specified missions. The IMM was used to forecast medical evacuation and loss of crew life probabilities, as well as crew health metrics for a near-earth asteroid (NEA) mission. An optimized medical kit for this mission was proposed based on the IMM simulation. Discussion The IMM can provide information to the space program regarding medical risks, including crew medical impairment, medical evacuation and loss of crew life. This information is valuable to mission managers and the space medicine community in assessing risk and developing mitigation strategies. Exploration missions such as NEA missions will have significant mass and volume constraints applied to the medical system. Appropriate allocation of medical resources will be critical to mission success. The IMM capability of optimizing medical systems based on specific crew and mission profiles will be advantageous to medical system designers. Conclusion The IMM is a decision support tool that can provide estimates of the impact of medical events on human space flight missions, such as crew impairment, evacuation, and loss of crew life. It can be used to support the development of mitigation strategies and to propose optimized medical systems for specified space flight missions. Learning Objectives The audience will learn how an evidence-based decision support tool can be used to help assess risk, develop mitigation strategies, and optimize medical systems for exploration space flight missions.

Biomolecular signatures of diabetic wound healing by structural mass spectrometry

PubMed Central

Hines, Kelly M.; Ashfaq, Samir; Davidson, Jeffrey M.; Opalenik, Susan R.; Wikswo, John P.; McLean, John A.

2013-01-01

Wound fluid is a complex biological sample containing byproducts associated with the wound repair process. Contemporary techniques, such as immunoblotting and enzyme immunoassays, require extensive sample manipulation and do not permit the simultaneous analysis of multiple classes of biomolecular species. Structural mass spectrometry, implemented as ion mobility-mass spectrometry (IM-MS), comprises two sequential, gas-phase dispersion techniques well suited for the study of complex biological samples due to its ability to separate and simultaneously analyze multiple classes of biomolecules. As a model of diabetic wound healing, polyvinyl alcohol (PVA) sponges were inserted subcutaneously into non-diabetic (control) and streptozotocin-induced diabetic rats to elicit a granulation tissue response and to collect acute wound fluid. Sponges were harvested at days 2 or 5 to capture different stages of the early wound healing process. Utilizing IM-MS, statistical analysis, and targeted ultra-performance liquid chromatography (UPLC) analysis, biomolecular signatures of diabetic wound healing have been identified. The protein S100-A8 was highly enriched in the wound fluids collected from day 2 diabetic rats. Lysophosphatidylcholine (20:4) and cholic acid also contributed significantly to the differences between diabetic and control groups. This report provides a generalized workflow for wound fluid analysis demonstrated with a diabetic rat model. PMID:23452326

Analysis of Advanced Respiratory Support Onboard ISS and CCV

NASA Technical Reports Server (NTRS)

Shah, Ronak V.; Kertsman, Eric L.; Alexander, David J.; Duchesne, Ted; Law, Jennifer; Roden, Sean K.

2014-01-01

NASA is collaborating with private entities for the development of commercial space vehicles. The Space and Clinical Operations Division was tasked to review the oxygen and respiratory support system and recommend what capabilities, if any, the vehicle should have to support the return of an ill or injured crewmember. The Integrated Medical Model (IMM) was utilized as a data source for the development of these recommendations. The Integrated Medical Model (IMM) was used to simulate a six month, six crew, International Space Station (ISS) mission. Three medical system scenarios were considered based on the availability of (1) oxygen only, (2) oxygen and a ventilator, or (3) neither oxygen nor ventilator. The IMM analysis provided probability estimates of medical events that would require either oxygen or ventilator support. It also provided estimates of crew health, the probability of evacuation, and the probability of loss of crew life secondary to medical events for each of the three medical system scenarios. These IMM outputs were used as objective data to enable evidence-based decisions regarding oxygen and respiratory support system requirements for commercial crew vehicles. The IMM provides data that may be utilized to support informed decisions regarding the development of medical systems for commercial crew vehicles.

The Integrated Medical Model

NASA Technical Reports Server (NTRS)

Kerstman, Eric; Minard, Charles; Saile, Lynn; Freiere deCarvalho, Mary; Myers, Jerry; Walton, Marlei; Butler, Douglas; Iyengar, Sriram; Johnson-Throop, Kathy; Baumann, David

2010-01-01

The goals of the Integrated Medical Model (IMM) are to develop an integrated, quantified, evidence-based decision support tool useful to crew health and mission planners and to help align science, technology, and operational activities intended to optimize crew health, safety, and mission success. Presentation slides address scope and approach, beneficiaries of IMM capabilities, history, risk components, conceptual models, development steps, and the evidence base. Space adaptation syndrome is used to demonstrate the model's capabilities.

A Preliminary Validation of Attention, Relevance, Confidence and Satisfaction Model-Based Instructional Material Motivational Survey in a Computer-Based Tutorial Setting

ERIC Educational Resources Information Center

Huang, Wenhao; Huang, Wenyeh; Diefes-Dux, Heidi; Imbrie, Peter K.

2006-01-01

This paper describes a preliminary validation study of the Instructional Material Motivational Survey (IMMS) derived from the Attention, Relevance, Confidence and Satisfaction motivational design model. Previous studies related to the IMMS, however, suggest its practical application for motivational evaluation in various instructional settings…

Characterization of two strains of selectively bred guinea-pigs. 2. Differences in immune response to synthetic polypeptides.

PubMed

Lundberg, L; Koch, C; Magnusson, M; Bertelsen, C

1983-06-01

Two strains of guinea-pigs selectively bred for either high (IMM/S) or low (IMM/R) responsiveness to ovalbumin-induced respiratory anaphylaxis were examined for their immune response to a copolymer of L-glutamic acid and L-alanine (GA), a copolymer of L-glutamic acid and L-tyrosine (GT), and to a dinitro-phenyl derivative of a homopolymer of L-lysine (DNP-PLL). Considerable differences between the strains in development of cellular hypersensitivity and in the production of antibodies were observed. Guinea-pigs from IMM/S were all responders to GA and DNP-PLL and non-responders to GT, while guinea-pigs from two of three lines from IMM/R were responders to GT and non-responders to GA and DNP-PLL. The third IMM/R line showed an immune response pattern similar to guinea-pigs of strain IMM/S. Preliminary breeding studies confirmed that the immune response to these three antigens is under the control of dominant autosomal genes, since (IMM/S x IMM/R) F1 animals responded to all three antigens. It is concluded that these three antigens may serve as immune response markers in genetic studies of the differences between guinea-pigs from IMM/S and IMM/R in their ability to develop respiratory anaphylaxis.

Problems In Indoor Mapping and Modelling

NASA Astrophysics Data System (ADS)

Zlatanova, S.; Sithole, G.; Nakagawa, M.; Zhu, Q.

2013-11-01

Research in support of indoor mapping and modelling (IMM) has been active for over thirty years. This research has come in the form of As-Built surveys, Data structuring, Visualisation techniques, Navigation models and so forth. Much of this research is founded on advancements in photogrammetry, computer vision and image analysis, computer graphics, robotics, laser scanning and many others. While IMM used to be the privy of engineers, planners, consultants, contractors, and designers, this is no longer the case as commercial enterprises and individuals are also beginning to apply indoor models in their business process and applications. There are three main reasons for this. Firstly, the last two decades have seen greater use of spatial information by enterprises and the public. Secondly, IMM has been complimented by advancements in mobile computing and internet communications, making it easier than ever to access and interact with spatial information. Thirdly, indoor modelling has been advanced geometrically and semantically, opening doors for developing user-oriented, context-aware applications. This reshaping of the public's attitude and expectations with regards to spatial information has realised new applications and spurred demand for indoor models and the tools to use them. This paper examines the present state of IMM and considers the research areas that deserve attention in the future. In particular the paper considers problems in IMM that are relevant to commercial enterprises and the general public, groups this paper expects will emerge as the greatest users IMM. The subject of indoor modelling and mapping is discussed here in terms of Acquisitions and Sensors, Data Structures and Modelling, Visualisation, Applications, Legal Issues and Standards. Problems are discussed in terms of those that exist and those that are emerging. Existing problems are those that are currently being researched. Emerging problems are those problems or demands that are expected to arise because of social changes, technological advancements, or commercial interests. The motivation of this work is to define a set of research problems that are either being investigated or should be investigated. These will hopefully provide a framework for assessing progress and advances in indoor modelling. The framework will be developed in the form of a problem matrix, detailing existing and emerging problems, their solutions and present best practices. Once the framework is complete it will be published online so that the IMM community can discuss and modify it as necessary. When the framework has reached a steady state an empirical benchmark will be provided to test solutions to posed problems. A yearly evaluation of the problem matrix will follow, the results of which will be published.

Functionally interpretable local coordinate systems for the upper extremity using inertial & magnetic measurement systems.

PubMed

de Vries, W H K; Veeger, H E J; Cutti, A G; Baten, C; van der Helm, F C T

2010-07-20

Inertial Magnetic Measurement Systems (IMMS) are becoming increasingly popular by allowing for measurements outside the motion laboratory. The latest models enable long term, accurate measurement of segment motion in terms of joint angles, if initial segment orientations can accurately be determined. The standard procedure for definition of segmental orientation is based on the measurement of positions of bony landmarks (BLM). However, IMMS do not deliver position information, so an alternative method to establish IMMS based, anatomically understandable segment orientations is proposed. For five subjects, IMMS recordings were collected in a standard anatomical position for definition of static axes, and during a series of standardized motions for the estimation of kinematic axes of rotation. For all axes, the intra- and inter-individual dispersion was estimated. Subsequently, local coordinate systems (LCS) were constructed on the basis of the combination of IMMS axes with the lowest dispersion and compared with BLM based LCS. The repeatability of the method appeared to be high; for every segment at least two axes could be determined with a dispersion of at most 3.8 degrees. Comparison of IMMS based with BLM based LCS yielded compatible results for the thorax, but less compatible results for the humerus, forearm and hand, where differences in orientation rose to 17.2 degrees. Although different from the 'gold standard' BLM based LCS, IMMS based LCS can be constructed repeatable, enabling the estimation of segment orientations outside the laboratory. A procedure for the definition of local reference frames using IMMS is proposed. 2010 Elsevier Ltd. All rights reserved.

Integrated Modeling, Mapping, and Simulation (IMMS) Framework for Exercise and Response Planning

NASA Technical Reports Server (NTRS)

Mapar, Jalal; Hoette, Trisha; Mahrous, Karim; Pancerella, Carmen M.; Plantenga, Todd; Yang, Christine; Yang, Lynn; Hopmeier, Michael

2011-01-01

EmergenCy management personnel at federal, stale, and local levels can benefit from the increased situational awareness and operational efficiency afforded by simulation and modeling for emergency preparedness, including planning, training and exercises. To support this goal, the Department of Homeland Security's Science & Technology Directorate is funding the Integrated Modeling, Mapping, and Simulation (IMMS) program to create an integrating framework that brings together diverse models for use by the emergency response community. SUMMIT, one piece of the IMMS program, is the initial software framework that connects users such as emergency planners and exercise developers with modeling resources, bridging the gap in expertise and technical skills between these two communities. SUMMIT was recently deployed to support exercise planning for National Level Exercise 2010. Threat, casualty. infrastructure, and medical surge models were combined within SUMMIT to estimate health care resource requirements for the exercise ground truth.

Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus).

PubMed

Aoki, N; Yamaguchi, S; Kitajima, T; Takehara, A; Katagiri-Nakagawa, S; Matsui, R; Watanabe, D; Matsushima, T; Homma, K J

2015-11-12

Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hierarchical structure of the energy landscape of proteins revisited by time series analysis. I. Mimicking protein dynamics in different time scales

NASA Astrophysics Data System (ADS)

Alakent, Burak; Camurdan, Mehmet C.; Doruker, Pemra

2005-10-01

Time series models, which are constructed from the projections of the molecular-dynamics (MD) runs on principal components (modes), are used to mimic the dynamics of two proteins: tendamistat and immunity protein of colicin E7 (ImmE7). Four independent MD runs of tendamistat and three independent runs of ImmE7 protein in vacuum are used to investigate the energy landscapes of these proteins. It is found that mean-square displacements of residues along the modes in different time scales can be mimicked by time series models, which are utilized in dividing protein dynamics into different regimes with respect to the dominating motion type. The first two regimes constitute the dominance of intraminimum motions during the first 5ps and the random walk motion in a hierarchically higher-level energy minimum, which comprise the initial time period of the trajectories up to 20-40ps for tendamistat and 80-120ps for ImmE7. These are also the time ranges within which the linear nonstationary time series are completely satisfactory in explaining protein dynamics. Encountering energy barriers enclosing higher-level energy minima constrains the random walk motion of the proteins, and pseudorelaxation processes at different levels of minima are detected in tendamistat, depending on the sampling window size. Correlation (relaxation) times of 30-40ps and 150-200ps are detected for two energy envelopes of successive levels for tendamistat, which gives an overall idea about the hierarchical structure of the energy landscape. However, it should be stressed that correlation times of the modes are highly variable with respect to conformational subspaces and sampling window sizes, indicating the absence of an actual relaxation. The random-walk step sizes and the time length of the second regime are used to illuminate an important difference between the dynamics of the two proteins, which cannot be clarified by the investigation of relaxation times alone: ImmE7 has lower-energy barriers enclosing the higher-level energy minimum, preventing the protein to relax and letting it move in a random-walk fashion for a longer period of time.

Autonomous, In-Flight Crew Health Risk Management for Exploration-Class Missions: Leveraging the Integrated Medical Model for the Exploration Medical System Demonstration Project

NASA Technical Reports Server (NTRS)

Butler, D. J.; Kerstman, E.; Saile, L.; Myers, J.; Walton, M.; Lopez, V.; McGrath, T.

2011-01-01

The Integrated Medical Model (IMM) captures organizational knowledge across the space medicine, training, operations, engineering, and research domains. IMM uses this knowledge in the context of a mission and crew profile to forecast risks to crew health and mission success. The IMM establishes a quantified, statistical relationship among medical conditions, risk factors, available medical resources, and crew health and mission outcomes. These relationships may provide an appropriate foundation for developing an in-flight medical decision support tool that helps optimize the use of medical resources and assists in overall crew health management by an autonomous crew with extremely limited interactions with ground support personnel and no chance of resupply.

Investigation of imatinib loaded surface decorated biodegradable nanocarriers against glioblastoma cell lines: Intracellular uptake and cytotoxicity studies.

PubMed

Khan, Abrar M; Ahmad, Farhan Jalees; Panda, Amulya K; Talegaonkar, Sushama

2016-06-30

Overexpression of P-glycoprotein (P-gp) efflux transporter in glioma cells thwarts the build-up of therapeutic concentration of drugs usually resulting into poor therapeutic outcome. To surmount aforesaid challenge, Imatinib (IMM) loaded Poly-lactide-co-glycolic acid nanoparticles (IMM-PLGA-NPs) were developed and optimized by Box Behnken Design as a new treatment stratagem in malignant glioma. Optimized NPs were functionalized with Pluronic(®) P84, P-gp inhibitor (IMM-PLGA-P84-NPs) which showed size, PDI, zeta potential, drug loading, 182.63±13.56nm, 0.196±0.021, -15.2±1.49mV, 40.63±2.04μg/mg, respectively. Intracellular uptake study conducted on A172, U251MG and C6 glioma cells demonstrated significantly high uptake of IMM through NPs when compared with IMM solution (IMM-S), p<0.001. IMM-PLGA-P84-NPs showed better uptake in P-gp expressing cell line (U251MG and C6) while uncoated NPs showed higher uptake in non-P-gp expressing cell line (A-172). Cytotoxicity studies demonstrated significantly low IC50 for both IMM-PLGA-NPs and IMM-PLGA-P84-NPs when compared with IC50 of IMM-S. IMM-PLGA-P84-NPs showed a significantly low IC50 against P-gp overexpressing cell lines when compared with IC50 of IMM-PLGA-NPs. In contrary, IMM-PLGA-NPs showed lower IC50 against non P-gp expressing cell line. This study demonstrated the feasibility of targeting surface decorated NPs to multidrug resistant gliomas. However, to address its clinical utility extensive in vivo studies are required. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization Routine for Generating Medical Kits for Spaceflight Using the Integrated Medical Model

NASA Technical Reports Server (NTRS)

Graham, Kimberli; Myers, Jerry; Goodenow, Deb

2017-01-01

The Integrated Medical Model (IMM) is a MATLAB model that provides probabilistic assessment of the medical risk associated with human spaceflight missions.Different simulations or profiles can be run in which input conditions regarding both mission characteristics and crew characteristics may vary. For each simulation, the IMM records the total medical events that occur and “treats” each event with resources drawn from import scripts. IMM outputs include Total Medical Events (TME), Crew Health Index (CHI), probability of Evacuation (pEVAC), and probability of Loss of Crew Life (pLOCL).The Crew Health Index is determined by the amount of quality time lost (QTL). Previously, an optimization code was implemented in order to efficiently generate medical kits. The kits were optimized to have the greatest benefit possible, given amass and/or volume constraint. A 6-crew, 14-day lunar mission was chosen for the simulation and run through the IMM for 100,000 trials. A built-in MATLAB solver, mixed-integer linear programming, was used for the optimization routine. Kits were generated in 10% increments ranging from 10%-100% of the benefit constraints. Conditions wheremass alone was minimized, volume alone was minimized, and where mass and volume were minimizedjointly were tested.

Modeling of defect tolerance of IMM multijunction photovoltaics for space application

NASA Astrophysics Data System (ADS)

Mehrotra, Akhil; Freundlich, Alex

2013-03-01

Reduction of defects by use of thick sophisticated graded metamorphic buffers in inverted metamorphic solar cells has been a requirement to obtain high efficiency devices. With increase in number of metamorphic junctions to obtain higher efficiencies, these graded buffers constitute a significant part of growth time and cost for manufacturer of the solar cells. It's been shown that ultrathin 3 and 4 junction IMM devices perform better in presence of dislocations or/and radiation harsh environment compared to conventional thick IMM devices. Thickness optimization of the device would result in better defect and radiation tolerant behavior of 0.7ev and 1.0ev InGaAs sub-cells which would in turn require thinner buffers with higher efficiencies, hence reducing the total device thickness. It is also shown that for 3 and 4 junc. IMM, with an equivalent 1015 cm-2 1 MeV electron fluence radiation, very high EOL efficiencies can be afforded with substantially higher dislocation densities (<2×107 cm-2) than those commonly perceived as acceptable for IMM devices with remaining power factor as high as 0.85. The irregular radiation degradation behavior in 4-junc IMM is also explained by back photon reflection from gold contacts and reduced by using thickness optimization of 0.7ev and 1.0ev InGaAs sub-cells.

Collision Cross Sections and Ion Mobility Separation of Fragment Ions from Complex N-Glycans.

PubMed

Harvey, David J; Watanabe, Yasunori; Allen, Joel D; Rudd, Pauline; Pagel, Kevin; Crispin, Max; Struwe, Weston B

2018-06-01

Ion mobility mass spectrometry (IM-MS) holds great potential for structural glycobiology, in particular in its ability to resolve glycan isomers. Generally, IM-MS has largely been applied to intact glycoconjugate ions with reports focusing on the separation of different adduct types. Here, we explore IM separation and report the collision cross section (CCS) of complex type N-glycans and their fragments in negative ion mode following collision-induced dissociation (CID). CCSs of isomeric fragment ions were found, in some cases, to reveal structural details that were not present in CID spectra themselves. Many fragment ions were confirmed as possessing multiple structure, details of which could be obtained by comparing their drift time profiles to different glycans. By using fragmentation both before and after mobility separation, information was gathered on the fragmentation pathways producing some of the ions. These results help demonstrate the utility of IM and will contribute to the growing use of IM-MS for glycomics. Graphical Abstract ᅟ.

Collision Cross Sections and Ion Mobility Separation of Fragment Ions from Complex N-Glycans

NASA Astrophysics Data System (ADS)

Harvey, David J.; Watanabe, Yasunori; Allen, Joel D.; Rudd, Pauline; Pagel, Kevin; Crispin, Max; Struwe, Weston B.

2018-04-01

Ion mobility mass spectrometry (IM-MS) holds great potential for structural glycobiology, in particular in its ability to resolve glycan isomers. Generally, IM-MS has largely been applied to intact glycoconjugate ions with reports focusing on the separation of different adduct types. Here, we explore IM separation and report the collision cross section (CCS) of complex type N-glycans and their fragments in negative ion mode following collision-induced dissociation (CID). CCSs of isomeric fragment ions were found, in some cases, to reveal structural details that were not present in CID spectra themselves. Many fragment ions were confirmed as possessing multiple structure, details of which could be obtained by comparing their drift time profiles to different glycans. By using fragmentation both before and after mobility separation, information was gathered on the fragmentation pathways producing some of the ions. These results help demonstrate the utility of IM and will contribute to the growing use of IM-MS for glycomics. [Figure not available: see fulltext.

Architecture Mapping of the Inner Mitochondrial Membrane Proteome by Chemical Tools in Live Cells.

PubMed

Lee, Song-Yi; Kang, Myeong-Gyun; Shin, Sanghee; Kwak, Chulhwan; Kwon, Taejoon; Seo, Jeong Kon; Kim, Jong-Seo; Rhee, Hyun-Woo

2017-03-15

The inner mitochondrial membrane (IMM) proteome plays a central role in maintaining mitochondrial physiology and cellular metabolism. Various important biochemical reactions such as oxidative phosphorylation, metabolite production, and mitochondrial biogenesis are conducted by the IMM proteome, and mitochondria-targeted therapeutics have been developed for IMM proteins, which is deeply related for various human metabolic diseases including cancer and neurodegenerative diseases. However, the membrane topology of the IMM proteome remains largely unclear because of the lack of methods to evaluate it in live cells in a high-throughput manner. In this article, we reveal the in vivo topological direction of 135 IMM proteins, using an in situ-generated radical probe with genetically targeted peroxidase (APEX). Owing to the short lifetime of phenoxyl radicals generated in situ by submitochondrial targeted APEX and the impermeability of the IMM to small molecules, the solvent-exposed tyrosine residues of both the matrix and intermembrane space (IMS) sides of IMM proteins were exclusively labeled with the radical probe in live cells by Matrix-APEX and IMS-APEX, respectively and identified by mass spectrometry. From this analysis, we confirmed 58 IMM protein topologies and we could determine the topological direction of 77 IMM proteins whose topology at the IMM has not been fully characterized. We also found several IMM proteins (e.g., LETM1 and OXA1) whose topological information should be revised on the basis of our results. Overall, our identification of structural information on the mitochondrial inner-membrane proteome can provide valuable insights for the architecture and connectome of the IMM proteome in live cells.

Validation of the Instructional Materials Motivation Survey (IMMS) in a Self-Directed Instructional Setting Aimed at Working with Technology

ERIC Educational Resources Information Center

Loorbach, Nicole; Peters, Oscar; Karreman, Joyce; Steehouder, Michaël

2015-01-01

The ARCS Model of Motivational Design has been used myriad times to design motivational instructions that focus on attention, relevance, confidence and satisfaction in order to motivate students. The Instructional Materials Motivation Survey (IMMS) is a 36-item situational measure of people's reactions to instructional materials in the light…

Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

PubMed

Durward-Akhurst, S A; Finno, C J; Barnes, N; Shivers, J; Guo, L T; Shelton, G D; Valberg, S J

2016-07-01

Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). Immunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed. Sarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles. Deficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Coming to Grips with Ambiguity: Ion Mobility-Mass Spectrometry for Protein Quaternary Structure Assignment

NASA Astrophysics Data System (ADS)

Eschweiler, Joseph D.; Frank, Aaron T.; Ruotolo, Brandon T.

2017-10-01

Multiprotein complexes are central to our understanding of cellular biology, as they play critical roles in nearly every biological process. Despite many impressive advances associated with structural characterization techniques, large and highly-dynamic protein complexes are too often refractory to analysis by conventional, high-resolution approaches. To fill this gap, ion mobility-mass spectrometry (IM-MS) methods have emerged as a promising approach for characterizing the structures of challenging assemblies due in large part to the ability of these methods to characterize the composition, connectivity, and topology of large, labile complexes. In this Critical Insight, we present a series of bioinformatics studies aimed at assessing the information content of IM-MS datasets for building models of multiprotein structure. Our computational data highlights the limits of current coarse-graining approaches, and compelled us to develop an improved workflow for multiprotein topology modeling, which we benchmark against a subset of the multiprotein complexes within the PDB. This improved workflow has allowed us to ascertain both the minimal experimental restraint sets required for generation of high-confidence multiprotein topologies, and quantify the ambiguity in models where insufficient IM-MS information is available. We conclude by projecting the future of IM-MS in the context of protein quaternary structure assignment, where we predict that a more complete knowledge of the ultimate information content and ambiguity within such models will undoubtedly lead to applications for a broader array of challenging biomolecular assemblies. [Figure not available: see fulltext.

Evaluation of the efficacy of intramuscular versus intramammary treatment of subclinical Streptococcus agalactiae mastitis in dairy cows in Colombia.

PubMed

Reyes, J; Chaffer, M; Sanchez, J; Torres, G; Macias, D; Jaramillo, M; Duque, P C; Ceballos, A; Keefe, G P

2015-08-01

A randomized controlled trial was performed in 17 Colombian dairy herds to determine the cure risk among cows subclinically infected with Streptococcus agalactiae exposed to 2 antibiotic therapies. Composite milk samples were collected before milking at the onset of the trial (pretreatment) and 2 subsequent times over a period of approximately 63 d. The intramammary application (IMM) of ampicillin-cloxacillin was compared with the intramuscular application (IM) of penethamate hydriodide, and cure risks after an initial and retreatment application were assessed. Cure risk after the initial treatment was higher (82.4%) for the IMM treatment than for IM therapy (65.8%). However, no difference was observed in the cure risk of refractory cases after retreatment (IMM=52.6% vs. IM=51.2%). The cumulative cure risk (both initial and retreatment) was 90.4 and 82.9% for the IMM and IM products, respectively. A 2-level random effects logistic model that controlled for pretreatment cow-level somatic cell count, indicated that IM treatment (odds ratio=0.37) had a lower cure risk than IMM and a tendency for a lower cure risk with increasing baseline somatic cell count. Our findings suggest that both products and administration routes can reduce the prevalence of S. agalactiae in affected herds, but the IMM product had a better efficacy in curing the infection. In addition to the treatment protocol, the cow somatic cell count should be considered when making management decisions for cows infected with S. agalactiae. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Bayesian Analysis for Risk Assessment of Selected Medical Events in Support of the Integrated Medical Model Effort

NASA Technical Reports Server (NTRS)

Gilkey, Kelly M.; Myers, Jerry G.; McRae, Michael P.; Griffin, Elise A.; Kallrui, Aditya S.

2012-01-01

The Exploration Medical Capability project is creating a catalog of risk assessments using the Integrated Medical Model (IMM). The IMM is a software-based system intended to assist mission planners in preparing for spaceflight missions by helping them to make informed decisions about medical preparations and supplies needed for combating and treating various medical events using Probabilistic Risk Assessment. The objective is to use statistical analyses to inform the IMM decision tool with estimated probabilities of medical events occurring during an exploration mission. Because data regarding astronaut health are limited, Bayesian statistical analysis is used. Bayesian inference combines prior knowledge, such as data from the general U.S. population, the U.S. Submarine Force, or the analog astronaut population located at the NASA Johnson Space Center, with observed data for the medical condition of interest. The posterior results reflect the best evidence for specific medical events occurring in flight. Bayes theorem provides a formal mechanism for combining available observed data with data from similar studies to support the quantification process. The IMM team performed Bayesian updates on the following medical events: angina, appendicitis, atrial fibrillation, atrial flutter, dental abscess, dental caries, dental periodontal disease, gallstone disease, herpes zoster, renal stones, seizure, and stroke.

Terrain mapping and control of unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Kang, Yeonsik

In this thesis, methods for terrain mapping and control of unmanned aerial vehicles (UAVs) are proposed. First, robust obstacle detection and tracking algorithm are introduced to eliminate the clutter noise uncorrelated with the real obstacle. This is an important problem since most types of sensor measurements are vulnerable to noise. In order to eliminate such noise, a Kalman filter-based interacting multiple model (IMM) algorithm is employed to effectively detect obstacles and estimate their positions precisely. Using the outcome of the IMM-based obstacle detection algorithm, a new method of building a probabilistic occupancy grid map is proposed based on Bayes rule in probability theory. Since the proposed map update law uses the outputs of the IMM-based obstacle detection algorithm, simultaneous tracking of moving targets and mapping of stationary obstacles are possible. This can be helpful especially in a noisy outdoor environment where different types of obstacles exist. Another feature of the algorithm is its capability to eliminate clutter noise as well as measurement noise. The proposed algorithm is simulated in Matlab using realistic sensor models. The results show close agreement with the layout of real obstacles. An efficient method called "quadtree" is used to process massive geographical information in a convenient manner. The algorithm is evaluated in a realistic simulation environment called RIPTIDE, which the NASA Ames Research Center developed to access the performance of complicated software for UAVs. Supposing that a UAV is equipped with abovementioned obstacle detection and mapping algorithm, the control problem of a small fixed-wing UAV is studied. A Nonlinear Model Predictive Control (NMPC is designed as a high level controller for the fixed-wing UAV using a kinematic model of the UAV. The kinematic model is employed because of the assumption that there exist low level controls on the UAV. The UAV dynamics are nonlinear with input constraints which is the main challenge explored in this thesis. The control objective of the NMPC is determined to track a desired line, and the analysis of the designed NMPC's stability is followed to find the conditions that can assure stability. Then, the control objective is extended to track adjoined multiple line segments with obstacle avoidance capability. In simulation, the performance of the NMPC is superb with fast convergence and small overshoot. The computation time is not a burden for a fixed-wing UAV controller with a Pentium level on-board computer that provides a reasonable control update rate.

A Hybrid Positioning Strategy for Vehicles in a Tunnel Based on RFID and In-Vehicle Sensors

PubMed Central

Song, Xiang; Li, Xu; Tang, Wencheng; Zhang, Weigong; Li, Bin

2014-01-01

Many intelligent transportation system applications require accurate, reliable, and continuous vehicle positioning. How to achieve such positioning performance in extended GPS-denied environments such as tunnels is the main challenge for land vehicles. This paper proposes a hybrid multi-sensor fusion strategy for vehicle positioning in tunnels. First, the preliminary positioning algorithm is developed. The Radio Frequency Identification (RFID) technology is introduced to achieve preliminary positioning in the tunnel. The received signal strength (RSS) is used as an indicator to calculate the distances between the RFID tags and reader, and then a Least Mean Square (LMS) federated filter is designed to provide the preliminary position information for subsequent global fusion. Further, to improve the positioning performance in the tunnel, an interactive multiple model (IMM)-based global fusion algorithm is developed to fuse the data from preliminary positioning results and low-cost in-vehicle sensors, such as electronic compasses and wheel speed sensors. In the actual implementation of IMM, the strong tracking extended Kalman filter (STEKF) algorithm is designed to replace the conventional extended Kalman filter (EKF) to achieve model individual filtering. Finally, the proposed strategy is evaluated through experiments. The results validate the feasibility and effectiveness of the proposed strategy. PMID:25490581

A hybrid positioning strategy for vehicles in a tunnel based on RFID and in-vehicle sensors.

PubMed

Song, Xiang; Li, Xu; Tang, Wencheng; Zhang, Weigong; Li, Bin

2014-12-05

Many intelligent transportation system applications require accurate, reliable, and continuous vehicle positioning. How to achieve such positioning performance in extended GPS-denied environments such as tunnels is the main challenge for land vehicles. This paper proposes a hybrid multi-sensor fusion strategy for vehicle positioning in tunnels. First, the preliminary positioning algorithm is developed. The Radio Frequency Identification (RFID) technology is introduced to achieve preliminary positioning in the tunnel. The received signal strength (RSS) is used as an indicator to calculate the distances between the RFID tags and reader, and then a Least Mean Square (LMS) federated filter is designed to provide the preliminary position information for subsequent global fusion. Further, to improve the positioning performance in the tunnel, an interactive multiple model (IMM)-based global fusion algorithm is developed to fuse the data from preliminary positioning results and low-cost in-vehicle sensors, such as electronic compasses and wheel speed sensors. In the actual implementation of IMM, the strong tracking extended Kalman filter (STEKF) algorithm is designed to replace the conventional extended Kalman filter (EKF) to achieve model individual filtering. Finally, the proposed strategy is evaluated through experiments. The results validate the feasibility and effectiveness of the proposed strategy.

Labeled RFS-Based Track-Before-Detect for Multiple Maneuvering Targets in the Infrared Focal Plane Array.

PubMed

Li, Miao; Li, Jun; Zhou, Yiyu

2015-12-08

The problem of jointly detecting and tracking multiple targets from the raw observations of an infrared focal plane array is a challenging task, especially for the case with uncertain target dynamics. In this paper a multi-model labeled multi-Bernoulli (MM-LMB) track-before-detect method is proposed within the labeled random finite sets (RFS) framework. The proposed track-before-detect method consists of two parts-MM-LMB filter and MM-LMB smoother. For the MM-LMB filter, original LMB filter is applied to track-before-detect based on target and measurement models, and is integrated with the interacting multiple models (IMM) approach to accommodate the uncertainty of target dynamics. For the MM-LMB smoother, taking advantage of the track labels and posterior model transition probability, the single-model single-target smoother is extended to a multi-model multi-target smoother. A Sequential Monte Carlo approach is also presented to implement the proposed method. Simulation results show the proposed method can effectively achieve tracking continuity for multiple maneuvering targets. In addition, compared with the forward filtering alone, our method is more robust due to its combination of forward filtering and backward smoothing.

Labeled RFS-Based Track-Before-Detect for Multiple Maneuvering Targets in the Infrared Focal Plane Array

PubMed Central

Li, Miao; Li, Jun; Zhou, Yiyu

2015-01-01

The problem of jointly detecting and tracking multiple targets from the raw observations of an infrared focal plane array is a challenging task, especially for the case with uncertain target dynamics. In this paper a multi-model labeled multi-Bernoulli (MM-LMB) track-before-detect method is proposed within the labeled random finite sets (RFS) framework. The proposed track-before-detect method consists of two parts—MM-LMB filter and MM-LMB smoother. For the MM-LMB filter, original LMB filter is applied to track-before-detect based on target and measurement models, and is integrated with the interacting multiple models (IMM) approach to accommodate the uncertainty of target dynamics. For the MM-LMB smoother, taking advantage of the track labels and posterior model transition probability, the single-model single-target smoother is extended to a multi-model multi-target smoother. A Sequential Monte Carlo approach is also presented to implement the proposed method. Simulation results show the proposed method can effectively achieve tracking continuity for multiple maneuvering targets. In addition, compared with the forward filtering alone, our method is more robust due to its combination of forward filtering and backward smoothing. PMID:26670234

Genome Wide Identification of the Immunophilin Gene Family in Leptosphaeria maculans: A Causal Agent of Blackleg Disease in Oilseed Rape (Brassica napus)

PubMed Central

Zouhar, Miloslav; Mazakova, Jana; Rysanek, Pavel

2014-01-01

Abstract Phoma stem canker (blackleg) is a disease of world-wide importance on oilseed rape (Brassica napus) and can cause serious losses for crops globally. The disease is caused by dothideomycetous fungus, Leptosphaeria maculans, which is highly virulent/aggressive. Cyclophilins (CYPs) and FK506-binding proteins (FKBPs) are ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) family. They are collectively referred to as immunophilins (IMMs). In the present study, IMM genes, CYP and FKBP in haploid strain v23.1.3 of L. maculans genome, were identified and classified. Twelve CYPs and five FKBPs were determined in total. Domain architecture analysis revealed the presence of a conserved cyclophilin-like domain (CLD) in the case of CYPs and FKBP_C in the case of FKBPs. Interestingly, IMMs in L. maculans also subgrouped into single domain (SD) and multidomain (MD) proteins. They were primarily found to be localized in cytoplasm, nuclei, and mitochondria. Homologous and orthologous gene pairs were also determined by comparison with the model organism Saccharomyces cerevisiae. Remarkably, IMMs of L. maculans contain shorter introns in comparison to exons. Moreover, CYPs, in contrast with FKBPs, contain few exons. However, two CYPs were determined as being intronless. The expression profile of IMMs in both mycelium and infected primary leaves of B. napus demonstrated their potential role during infection. Secondary structure analysis revealed the presence of atypical eight β strands and two α helices fold architecture. Gene ontology analysis of IMMs predicted their significant role in protein folding and PPIase activity. Taken together, our findings for the first time present new prospects of this highly conserved gene family in phytopathogenic fungus. PMID:25259854

ECP Bone Workshop Day 2, Session 1: Validation of Exercise Countermeasures

NASA Technical Reports Server (NTRS)

Myers, Jerry G.

2007-01-01

The thesis of this session of the ECP Bone workshop is that computer modeling is required in order to evaluate factor of risk for fracture when considering the uniquely localized bone loss conditions experienced by Astronauts. This session provides an opportunity to introduce the Integrated Medical Model Bone Fracture Risk (IMM-BFxRM) simulation approach and how this and other models improve understanding of the effects of exercise countermeasures. This workshop session also provides an opportunity for the panel to provide recommendations on this and other "complex modeling" approaches, as well as, the importance of funding the IMM-BFxRM and companion efforts by external scientists (Lang and Keyak).

Integration of an Evidence Base into a Probabilistic Risk Assessment Model. The Integrated Medical Model Database: An Organized Evidence Base for Assessing In-Flight Crew Health Risk and System Design

NASA Technical Reports Server (NTRS)

Saile, Lynn; Lopez, Vilma; Bickham, Grandin; FreiredeCarvalho, Mary; Kerstman, Eric; Byrne, Vicky; Butler, Douglas; Myers, Jerry; Walton, Marlei

2011-01-01

This slide presentation reviews the Integrated Medical Model (IMM) database, which is an organized evidence base for assessing in-flight crew health risk. The database is a relational database accessible to many people. The database quantifies the model inputs by a ranking based on the highest value of the data as Level of Evidence (LOE) and the quality of evidence (QOE) score that provides an assessment of the evidence base for each medical condition. The IMM evidence base has already been able to provide invaluable information for designers, and for other uses.

Regulation of gene expression in plasmid ColE1: delayed expression of the kil gene.

PubMed Central

Zhang, S P; Yan, L F; Zubay, G

1988-01-01

cea, imm, and kil are a cluster of three functionally related genes of the plasmid ColE1. The cea and kil genes are in the same inducible operon, with transcription being initiated from a promoter adjacent to the cea gene. The imm gene is located between the cea and kil genes, but it is transcribed in the opposite direction. Complementary interaction between the imm mRNA and the anti-imm sequences in the middle of the cea-kil transcript causes a pronounced delay in expression of the kil gene when the cea-kil operon is induced. A segment in the overlapping region between the cea and imm genes causes delayed expression of the kil gene in the absence of imm gene transcription. This delay effect increases the yields of colicin synthesized in induced cells. Images PMID:3142845

Multiple-hypothesis multiple-model line tracking

NASA Astrophysics Data System (ADS)

Pace, Donald W.; Owen, Mark W.; Cox, Henry

2000-07-01

Passive sonar signal processing generally includes tracking of narrowband and/or broadband signature components observed on a Lofargram or on a Bearing-Time-Record (BTR) display. Fielded line tracking approaches to date have been recursive and single-hypthesis-oriented Kalman- or alpha-beta filters, with no mechanism for considering tracking alternatives beyond the most recent scan of measurements. While adaptivity is often built into the filter to handle changing track dynamics, these approaches are still extensions of single target tracking solutions to multiple target tracking environment. This paper describes an application of multiple-hypothesis, multiple target tracking technology to the sonar line tracking problem. A Multiple Hypothesis Line Tracker (MHLT) is developed which retains the recursive minimum-mean-square-error tracking behavior of a Kalman Filter in a maximum-a-posteriori delayed-decision multiple hypothesis context. Multiple line track filter states are developed and maintained using the interacting multiple model (IMM) state representation. Further, the data association and assignment problem is enhanced by considering line attribute information (line bandwidth and SNR) in addition to beam/bearing and frequency fit. MHLT results on real sonar data are presented to demonstrate the benefits of the multiple hypothesis approach. The utility of the system in cluttered environments and particularly in crossing line situations is shown.

Advancing the large-scale CCS database for metabolomics and lipidomics at the machine-learning era.

PubMed

Zhou, Zhiwei; Tu, Jia; Zhu, Zheng-Jiang

2018-02-01

Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in complex biological samples. The collision cross-section (CCS) value derived from IM-MS is a valuable physiochemical property for the unambiguous identification of metabolites and lipids. However, CCS values obtained from experimental measurement and computational modeling are limited available, which significantly restricts the application of IM-MS. In this review, we will discuss the recently developed machine-learning based prediction approach, which could efficiently generate precise CCS databases in a large scale. We will also highlight the applications of CCS databases to support metabolomics and lipidomics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sizing and Discovery of Nanosized Polyoxometalate Clusters by Mass Spectrometry

PubMed Central

2016-01-01

Ion mobility-mass spectrometry (IM-MS) is a powerful technique for structural characterization, e.g., sizing and conformation, particularly when combined with quantitative modeling and comparison to theoretical values. Traveling wave IM-MS (TW-IM-MS) has recently become commercially available to nonspecialist groups and has been exploited in the structural study of large biomolecules, however reliable calibrants for large anions have not been available. Polyoxometalate (POM) species—nanoscale inorganic anions—share many of the facets of large biomolecules, however, the full potential of IM-MS in their study has yet to be realized due to a lack of suitable calibration data or validated theoretical models. Herein we address these limitations by reporting DT-IM (drift tube) data for a set of POM clusters {M12} Keggin 1, {M18} Dawson 2, and two {M7} Anderson derivatives 3 and 4 which demonstrate their use as a TW-IM-MS calibrant set to facilitate characterization of very large (ca. 1–4 nm) anionic species. The data was also used to assess the validity of standard techniques to model the collision cross sections of large inorganic anions using the nanoscale family of compounds based upon the {Se2W29} unit including the trimer, {Se8W86O299} A, tetramer, {Se8W116O408} B, and hexamer {Se12W174O612} C, including their relative sizing in solution. Furthermore, using this data set, we demonstrated how IM-MS can be used to conveniently characterize and identify the synthesis of two new, i.e., previously unreported POM species, {P8W116}, unknown D, and {Te8W116}, unknown E, which are not amenable to analysis by other means with the approximate formulation of [H34W118X8M2O416]44–, where X = P and M = Co for D and X = Te and M = Mn for E. This work establishes a new type of inorganic calibrant for IM-MS allowing sizing, structural analysis, and discovery of molecular nanostructures directly from solution. PMID:26906879

Comparison of two polymer-based immunohistochemical detection systems: ENVISION+ and ImmPRESS.

PubMed

Ramos-Vara, José A; Miller, Margaret A

2006-11-01

The non-specific background reaction produced in avidin-biotin-based immunohistochemistry, particularly after harsh antigen retrieval procedures, has promoted the use of non-avidin-biotin systems, yet there are few reports comparing the performance of non-avidin-biotin, polymer-based methods. In this study we compare two of these methods, ENVISION+trade mark and ImmPRESS, in animal tissues. We examined the immunoreactivity of 18 antigens in formalin-fixed, paraffin-embedded tissues. Antigens were located in the cytoplasmic membrane (CD11d, CD18 and CD79a), cytoplasm (calretinin, COX-1, COX-2, Glut-1, HepPar 1, KIT, Melan A, tryptase and uroplakin III) or nucleus (MUM-1, PGP 9.5 and thyroid transcription factor 1). We also evaluated three infectious agents (Aspergillus, calicivirus and West Nile virus). The staining with ENVISION+ or ImmPRESS was performed simultaneously for each antigen. The intensity of the reaction and background staining were scored. ImmPRESS yielded similar or higher reaction intensity than ENVISION+trade mark in 16/18 antigens. ImmPRESS produced abundant background with the other two antigens (calretinin and COX-2), which hindered interpretation of the specific reaction. The cost of ImmPRESS was 25% lower than for ENVISION+trade mark. Based on these results, ImmPRESS is a good polymer-based detection system for routine immunohistochemistry.

Recent progress of Spectrolab high-efficiency space solar cells

NASA Astrophysics Data System (ADS)

Law, Daniel C.; Boisvert, J. C.; Rehder, E. M.; Chiu, P. T.; Mesropian, S.; Woo, R. L.; Liu, X. Q.; Hong, W. D.; Fetzer, C. M.; Singer, S. B.; Bhusari, D. M.; Edmondson, K. M.; Zakaria, A.; Jun, B.; Krut, D. D.; King, R. R.; Sharma, S. K.; Karam, N. H.

2013-09-01

Recent progress in III-V multijunction space solar cell has led to Spectrolab's GaInP/GaAs/Ge triple-junction, XTJ, cells with average 1-sun efficiency of 29% (AM0, 28°C) for cell size ranging from 59 to 72-cm2. High-efficiency inverted metamorphic (IMM) multijunction cells are developed as the next space solar cell architecture. Spectrolab's large-area IMM3J and IMM4J cells have achieved 33% and 34% 1-sun, AM0 efficiencies, respectively. The IMM3J and the IMM4J cells have both demonstrated normalized power retention of 0.86 at 5x1014 e-/cm2 fluence and 0.83 and 0.82 at 1x1015 e-/cm2 fluence post 1-MeV electron radiation, respectively. The IMM cells were further assembled into coverglass-interconnect-cell (CIC) strings and affixed to typical rigid aluminum honeycomb panels for thermal cycling characterization. Preliminary temperature cycling data of two coupons populated with IMM cell strings showed no performance degradation. Spectrolab has also developed semiconductor bonded technology (SBT) where highperformance component subcells were grown on GaAs and InP substrates separately then bonded directly to form the final multijunction cells. Large-area SBT 5-junction cells have achieved a 35.1% efficiency under 1-sun, AM0 condition.

Fuzzy adaptive interacting multiple model nonlinear filter for integrated navigation sensor fusion.

PubMed

Tseng, Chien-Hao; Chang, Chih-Wen; Jwo, Dah-Jing

2011-01-01

In this paper, the application of the fuzzy interacting multiple model unscented Kalman filter (FUZZY-IMMUKF) approach to integrated navigation processing for the maneuvering vehicle is presented. The unscented Kalman filter (UKF) employs a set of sigma points through deterministic sampling, such that a linearization process is not necessary, and therefore the errors caused by linearization as in the traditional extended Kalman filter (EKF) can be avoided. The nonlinear filters naturally suffer, to some extent, the same problem as the EKF for which the uncertainty of the process noise and measurement noise will degrade the performance. As a structural adaptation (model switching) mechanism, the interacting multiple model (IMM), which describes a set of switching models, can be utilized for determining the adequate value of process noise covariance. The fuzzy logic adaptive system (FLAS) is employed to determine the lower and upper bounds of the system noise through the fuzzy inference system (FIS). The resulting sensor fusion strategy can efficiently deal with the nonlinear problem for the vehicle navigation. The proposed FUZZY-IMMUKF algorithm shows remarkable improvement in the navigation estimation accuracy as compared to the relatively conventional approaches such as the UKF and IMMUKF.

The Impact of Health Literacy Status on the Comparative Validity and Sensitivity of an Interactive Multimedia Beverage Intake Questionnaire.

PubMed

Hooper, Lucy P; Myers, Emily A; Zoellner, Jamie M; Davy, Brenda M; Hedrick, Valisa E

2016-12-23

Self-reported dietary assessment methods can be challenging to validate, and reporting errors for those with lower health literacy (HL) may be augmented. Interactive multimedia (IMM) based questionnaires could help overcome these limitations. The objectives of this investigation are to assess the comparative validity and sensitivity to change of an IMM beverage intake questionnaire (IMM-BEVQ) as compared to dietary recalls and determine the impact of HL. Adults completed three 24-h dietary recalls and the IMM-BEVQ at baseline and after a six-month intervention targeting either sugar-sweetened beverages (SSB) or physical activity. Correlations and paired-samples t -tests are presented. For validity ( n = 273), intake of SSB (mean difference = 10.6 fl oz) and total beverage consumption (mean difference = 16.0 fl oz) were significantly different ( p ≤ 0.001) at baseline between the IMM-BEVQ and dietary recalls for all participants. However, the differences in intake were generally greater in low HL participants than in adequate HL participants. For sensitivity ( n = 162), change in SSB intake (mean difference = 7.2 fl oz) was significantly different ( p ≤ 0.01) between pre-/post-IMM-BEVQ and pre-/post-dietary recalls, but not total beverage intake (mean difference = 7.6 fl oz) for all participants. Changes in SSB and total beverage intake were not significantly different for those with adequate HL. The IMM-BEVQ is a valid dietary assessment tool that is as responsive to detecting changes in beverage intake as dietary recalls. However, adults with lower HL may need additional guidance when completing the IMM-BEVQ.

Lightweight IMM PV Flexible Blanket Assembly

NASA Technical Reports Server (NTRS)

Spence, Brian

2015-01-01

Deployable Space Systems (DSS) has developed an inverted metamorphic multijunction (IMM) photovoltaic (PV) integrated modular blanket assembly (IMBA) that can be rolled or z-folded. This IMM PV IMBA technology enables a revolutionary flexible PV blanket assembly that provides high specific power, exceptional stowed packaging efficiency, and high-voltage operation capability. DSS's technology also accommodates standard third-generation triple junction (ZTJ) PV device technologies to provide significantly improved performance over the current state of the art. This SBIR project demonstrated prototype, flight-like IMM PV IMBA panel assemblies specifically developed, designed, and optimized for NASA's high-voltage solar array missions.

Polar versus Cartesian velocity models for maneuvering target tracking with IMM

NASA Astrophysics Data System (ADS)

Laneuville, Dann

This paper compares various model sets in different IMM filters for the maneuvering target tracking problem. The aim is to see whether we can improve the tracking performance of what is certainly the most widely used model set in the literature for the maneuvering target tracking problem: a Nearly Constant Velocity model and a Nearly Coordinated Turn model. Our new challenger set consists of a mixed Cartesian position and polar velocity state vector to describe the uniform motion segments and is augmented with the turn rate to obtain the second model for the maneuvering segments. This paper also gives a general procedure to discretize up to second order any non-linear continuous time model with linear diffusion. Comparative simulations on an air defence scenario with a 2D radar, show that this new approach improves significantly the tracking performance in this case.

The Impact of Health Literacy Status on the Comparative Validity and Sensitivity of an Interactive Multimedia Beverage Intake Questionnaire

PubMed Central

Hooper, Lucy P.; Myers, Emily A.; Zoellner, Jamie M.; Davy, Brenda M.; Hedrick, Valisa E.

2016-01-01

Self-reported dietary assessment methods can be challenging to validate, and reporting errors for those with lower health literacy (HL) may be augmented. Interactive multimedia (IMM) based questionnaires could help overcome these limitations. The objectives of this investigation are to assess the comparative validity and sensitivity to change of an IMM beverage intake questionnaire (IMM-BEVQ) as compared to dietary recalls and determine the impact of HL. Adults completed three 24-h dietary recalls and the IMM-BEVQ at baseline and after a six-month intervention targeting either sugar-sweetened beverages (SSB) or physical activity. Correlations and paired-samples t-tests are presented. For validity (n = 273), intake of SSB (mean difference = 10.6 fl oz) and total beverage consumption (mean difference = 16.0 fl oz) were significantly different (p ≤ 0.001) at baseline between the IMM-BEVQ and dietary recalls for all participants. However, the differences in intake were generally greater in low HL participants than in adequate HL participants. For sensitivity (n = 162), change in SSB intake (mean difference = 7.2 fl oz) was significantly different (p ≤ 0.01) between pre-/post-IMM-BEVQ and pre-/post-dietary recalls, but not total beverage intake (mean difference = 7.6 fl oz) for all participants. Changes in SSB and total beverage intake were not significantly different for those with adequate HL. The IMM-BEVQ is a valid dietary assessment tool that is as responsive to detecting changes in beverage intake as dietary recalls. However, adults with lower HL may need additional guidance when completing the IMM-BEVQ. PMID:28025538

Assessment of Medical Risks and Optimization of their Management using Integrated Medical Model

NASA Technical Reports Server (NTRS)

Fitts, Mary A.; Madurai, Siram; Butler, Doug; Kerstman, Eric; Risin, Diana

2008-01-01

The Integrated Medical Model (IMM) Project is a software-based technique that will identify and quantify the medical needs and health risks of exploration crew members during space flight and evaluate the effectiveness of potential mitigation strategies. The IMM Project employs an evidence-based approach that will quantify probability and consequences of defined in-flight medical risks, mitigation strategies, and tactics to optimize crew member health. Using stochastic techniques, the IMM will ultimately inform decision makers at both programmatic and institutional levels and will enable objective assessment of crew health and optimization of mission success using data from relevant cohort populations and from the astronaut population. The objectives of the project include: 1) identification and documentation of conditions that may occur during exploration missions (Baseline Medical Conditions List [BMCL), 2) assessment of the likelihood of conditions in the BMCL occurring during exploration missions (incidence rate), 3) determination of the risk associated with these conditions and quantify in terms of end states (Loss of Crew, Loss of Mission, Evacuation), 4) optimization of in-flight hardware mass, volume, power, bandwidth and cost for a given level of risk or uncertainty, and .. validation of the methodologies used.

The Integrated Medical Model - Optimizing In-flight Space Medical Systems to Reduce Crew Health Risk and Mission Impacts

NASA Technical Reports Server (NTRS)

Kerstman, Eric; Walton, Marlei; Minard, Charles; Saile, Lynn; Myers, Jerry; Butler, Doug; Lyengar, Sriram; Fitts, Mary; Johnson-Throop, Kathy

2009-01-01

The Integrated Medical Model (IMM) is a decision support tool used by medical system planners and designers as they prepare for exploration planning activities of the Constellation program (CxP). IMM provides an evidence-based approach to help optimize the allocation of in-flight medical resources for a specified level of risk within spacecraft operational constraints. Eighty medical conditions and associated resources are represented in IMM. Nine conditions are due to Space Adaptation Syndrome. The IMM helps answer fundamental medical mission planning questions such as What medical conditions can be expected? What type and quantity of medical resources are most likely to be used?", and "What is the probability of crew death or evacuation due to medical events?" For a specified mission and crew profile, the IMM effectively characterizes the sequence of events that could potentially occur should a medical condition happen. The mathematical relationships among mission and crew attributes, medical conditions and incidence data, in-flight medical resources, potential clinical and crew health end states are established to generate end state probabilities. A Monte Carlo computational method is used to determine the probable outcomes and requires up to 25,000 mission trials to reach convergence. For each mission trial, the pharmaceuticals and supplies required to diagnose and treat prevalent medical conditions are tracked and decremented. The uncertainty of patient response to treatment is bounded via a best-case, worst-case, untreated case algorithm. A Crew Health Index (CHI) metric, developed to account for functional impairment due to a medical condition, provides a quantified measure of risk and enables risk comparisons across mission scenarios. The use of historical in-flight medical data, terrestrial surrogate data as appropriate, and space medicine subject matter expertise has enabled the development of a probabilistic, stochastic decision support tool capable of optimizing in-flight medical systems based on crew and mission parameters. This presentation will illustrate how to apply quantitative risk assessment methods to optimize the mass and volume of space-based medical systems for a space flight mission given the level of crew health and mission risk.

Mass and Volume Optimization of Space Flight Medical Kits

NASA Technical Reports Server (NTRS)

Keenan, A. B.; Foy, Millennia Hope; Myers, Jerry

2014-01-01

Resource allocation is a critical aspect of space mission planning. All resources, including medical resources, are subject to a number of mission constraints such a maximum mass and volume. However, unlike many resources, there is often limited understanding in how to optimize medical resources for a mission. The Integrated Medical Model (IMM) is a probabilistic model that estimates medical event occurrences and mission outcomes for different mission profiles. IMM simulates outcomes and describes the impact of medical events in terms of lost crew time, medical resource usage, and the potential for medically required evacuation. Previously published work describes an approach that uses the IMM to generate optimized medical kits that maximize benefit to the crew subject to mass and volume constraints. We improve upon the results obtained previously and extend our approach to minimize mass and volume while meeting some benefit threshold. METHODS We frame the medical kit optimization problem as a modified knapsack problem and implement an algorithm utilizing dynamic programming. Using this algorithm, optimized medical kits were generated for 3 mission scenarios with the goal of minimizing the medical kit mass and volume for a specified likelihood of evacuation or Crew Health Index (CHI) threshold. The algorithm was expanded to generate medical kits that maximize likelihood of evacuation or CHI subject to mass and volume constraints. RESULTS AND CONCLUSIONS In maximizing benefit to crew health subject to certain constraints, our algorithm generates medical kits that more closely resemble the unlimited-resource scenario than previous approaches which leverage medical risk information generated by the IMM. Our work here demonstrates that this algorithm provides an efficient and effective means to objectively allocate medical resources for spaceflight missions and provides an effective means of addressing tradeoffs in medical resource allocations and crew mission success parameters.

The Integrated Medical Model: A Decision Support Tool for In-flight Crew Health Care

NASA Technical Reports Server (NTRS)

Butler, Doug

2009-01-01

This viewgraph presentation reviews the development of an Integrated Medical Model (IMM) decision support tool for in-flight crew health care safety. Clinical methods, resources, and case scenarios are also addressed.

Investigation of sliding DNA clamp dynamics by single-molecule fluorescence, mass spectrometry and structure-based modeling

PubMed Central

Gadkari, Varun V; Harvey, Sophie R; Raper, Austin T; Chu, Wen-Ting; Wang, Jin; Wysocki, Vicki H; Suo, Zucai

2018-01-01

Abstract Proliferating cell nuclear antigen (PCNA) is a trimeric ring-shaped clamp protein that encircles DNA and interacts with many proteins involved in DNA replication and repair. Despite extensive structural work to characterize the monomeric, dimeric, and trimeric forms of PCNA alone and in complex with interacting proteins, no structure of PCNA in a ring-open conformation has been published. Here, we use a multidisciplinary approach, including single-molecule Förster resonance energy transfer (smFRET), native ion mobility-mass spectrometry (IM-MS), and structure-based computational modeling, to explore the conformational dynamics of a model PCNA from Sulfolobus solfataricus (Sso), an archaeon. We found that Sso PCNA samples ring-open and ring-closed conformations even in the absence of its clamp loader complex, replication factor C, and transition to the ring-open conformation is modulated by the ionic strength of the solution. The IM-MS results corroborate the smFRET findings suggesting that PCNA dynamics are maintained in the gas phase and further establishing IM-MS as a reliable strategy to investigate macromolecular motions. Our molecular dynamic simulations agree with the experimental data and reveal that ring-open PCNA often adopts an out-of-plane left-hand geometry. Collectively, these results implore future studies to define the roles of PCNA dynamics in DNA loading and other PCNA-mediated interactions. PMID:29529283

Risks from Solar Particle Events for Long Duration Space Missions Outside Low Earth Orbit

NASA Technical Reports Server (NTRS)

Over, S.; Myers, J.; Ford, J.

2016-01-01

The Integrated Medical Model (IMM) simulates the medical occurrences and mission outcomes for various mission profiles using probabilistic risk assessment techniques. As part of the work with the Integrated Medical Model (IMM), this project focuses on radiation risks from acute events during extended human missions outside low Earth orbit (LEO). Of primary importance in acute risk assessment are solar particle events (SPEs), which are low probability, high consequence events that could adversely affect mission outcomes through acute radiation damage to astronauts. SPEs can be further classified into coronal mass ejections (CMEs) and solar flares/impulsive events (Fig. 1). CMEs are an eruption of solar material and have shock enhancements that contribute to make these types of events higher in total fluence than impulsive events.

Classification of rice (Oryza sativa L. Japonica nipponbare) immunophilins (FKBPs, CYPs) and expression patterns under water stress.

PubMed

Ahn, Jun Cheul; Kim, Dae-Won; You, Young Nim; Seok, Min Sook; Park, Jeong Mee; Hwang, Hyunsik; Kim, Beom-Gi; Luan, Sheng; Park, Hong-Seog; Cho, Hye Sun

2010-11-18

FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding. They are collectively referred to as immunophilin (IMM), being present in almost all cellular organs. In particular, a number of IMMs relate to environmental stresses. FKBP and CYP proteins in rice (Oryza sativa cv. Japonica) were identified and classified, and given the appropriate name for each IMM, considering the ortholog-relation with Arabidopsis and Chlamydomonas or molecular weight of the proteins. 29 FKBP and 27 CYP genes can putatively be identified in rice; among them, a number of genes can be putatively classified as orthologs of Arabidopsis IMMs. However, some genes were novel, did not match with those of Arabidopsis and Chlamydomonas, and several genes were paralogs by genetic duplication. Among 56 IMMs in rice, a significant number are regulated by salt and/or desiccation stress. In addition, their expression levels responding to the water-stress have been analyzed in different tissues, and some subcellular IMMs located by means of tagging with GFP protein. Like other green photosynthetic organisms such as Arabidopsis (23 FKBPs and 29 CYPs) and Chlamydomonas (23 FKBs and 26 CYNs), rice has the highest number of IMM genes among organisms reported so far, suggesting that the numbers relate closely to photosynthesis. Classification of the putative FKBPs and CYPs in rice provides the information about their evolutional/functional significance when comparisons are drawn with the relatively well studied genera, Arabidopsis and Chlamydomonas. In addition, many of the genes upregulated by water stress offer the possibility of manipulating the stress responses in rice.

Combining tabular, rule-based, and procedural knowledge in computer-based guidelines for childhood immunization.

PubMed

Miller, P L; Frawley, S J; Sayward, F G; Yasnoff, W A; Duncan, L; Fleming, D W

1997-06-01

IMM/Serve is a computer program which implements the clinical guidelines for childhood immunization. IMM/Serve accepts as input a child's immunization history. It then indicates which vaccinations are due and which vaccinations should be scheduled next. The clinical guidelines for immunization are quite complex and are modified quite frequently. As a result, it is important that IMM/Serve's knowledge be represented in a format that facilitates the maintenance of that knowledge as the field evolves over time. To achieve this goal, IMM/Serve uses four representations for different parts of its knowledge base: (1) Immunization forecasting parameters that specify the minimum ages and wait-intervals for each dose are stored in tabular form. (2) The clinical logic that determines which set of forecasting parameters applies for a particular patient in each vaccine series is represented using if-then rules. (3) The temporal logic that combines dates, ages, and intervals to calculate recommended dates, is expressed procedurally. (4) The screening logic that checks each previous dose for validity is performed using a decision table that combines minimum ages and wait intervals with a small amount of clinical logic. A knowledge maintenance tool, IMM/Def, has been developed to help maintain the rule-based logic. The paper describes the design of IMM/Serve and the rationale and role of the different forms of knowledge used.

Long-Term Anti-Allodynic Effect of Immediate Pulsed Radiofrequency Modulation through Down-Regulation of Insulin-Like Growth Factor 2 in a Neuropathic Pain Model.

PubMed

Yeh, Chun-Chang; Sun, Hsiao-Lun; Huang, Chi-Jung; Wong, Chih-Shung; Cherng, Chen-Hwan; Huh, Billy Keon; Wang, Jinn-Shyan; Chien, Chih-Cheng

2015-11-13

Pulsed radiofrequency (PRF) is effective in the treatment of neuropathic pain in clinical practice. Its application to sites proximal to nerve injury can inhibit the activity of extra-cellular signal-regulated kinase (ERK) for up to 28 days. The spared nerve injury (SNI)+ immPRF group (immediate exposure to PRF for 6 min after SNI) exhibited a greater anti-allodynic effect compared with the control group (SNI alone) or the SNI + postPRF group (application of PRF for 6 min on the 14th day after SNI). Insulin-like growth factor 2 (IGF2) was selected using microarray assays and according to web-based gene ontology annotations in the SNI + immPRF group. An increase in IGF2 and activation of ERK1/2 were attenuated by the immPRF treatment compared with an SNI control group. Using immunofluorescent staining, we detected co-localized phosphorylated ERK1/2 and IGF2 in the dorsal horn regions of rats from the SNI group, where the IGF2 protein predominantly arose in CD11b- or NeuN-positive cells, whereas IGF2 immunoreactivity was not detected in the SNI + immPRF group. Taken together, these results suggest that PRF treatment immediately after nerve injury significantly inhibited the development of neuropathic pain with a lasting effect, most likely through IGF2 down-regulation and the inhibition of ERK1/2 activity primarily in microglial cells.

CoMIC, the hidden dynamics of mitochondrial inner compartments

PubMed Central

Cho, Bongki; Sun, Woong

2017-01-01

Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood. Recently, we found that the IMM and the inner compartments undergo transient and reversible constriction prior to the OMM division, which we termed CoMIC, Constriction of Mitochondrial Inner Compartment. In this short review, we further discuss the evolutionary perspective and the regulatory mechanism of CoMIC during mitochondrial division. PMID:28803609

CoMIC, the hidden dynamics of mitochondrial inner compartments.

PubMed

Cho, Bongki; Sun, Woong

2017-12-01

Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood. Recently, we found that the IMM and the inner compartments undergo transient and reversible constriction prior to the OMM division, which we termed CoMIC, Constriction of Mitochondrial Inner Compartment. In this short review, we further discuss the evolutionary perspective and the regulatory mechanism of CoMIC during mitochondrial division. [BMB Reports 2017; 50(12): 597-598].

Integrated Display and Simulation for Automatic Dependent Surveillance-Broadcast and Traffic Collision Avoidance System Data Fusion.

PubMed

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-11-13

Automatic Dependent Surveillance-Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications.

Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states

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

Banco, Michael T.; Mishra, Vidhi; Ostermann, Andreas

2016-11-16

MTAN (5'-methylthioadenosine nucleosidase) catalyzes the hydrolysis of the N-ribosidic bond of a variety of adenosine-containing metabolites. The Helicobacter pylori MTAN (HpMTAN) hydrolyzes 6-amino-6-deoxyfutalosine in the second step of the alternative menaquinone biosynthetic pathway. Substrate binding of the adenine moiety is mediated almost exclusively by hydrogen bonds, and the proposed catalytic mechanism requires multiple proton-transfer events. Of particular interest is the protonation state of residue D198, which possesses a pKa above 8 and functions as a general acid to initiate the enzymatic reaction. In this study we present three corefined neutron/X-ray crystal structures of wild-type HpMTAN cocrystallized with S-adenosylhomocysteine (SAH), Formycinmore » A (FMA), and (3R,4S)-4-(4-Chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine (p-ClPh-Thio-DADMe-ImmA) as well as one neutron/X-ray crystal structure of an inactive variant (HpMTAN-D198N) cocrystallized with SAH. These results support a mechanism of D198 pKa elevation through the unexpected sharing of a proton with atom N7 of the adenine moiety possessing unconventional hydrogen-bond geometry. Additionally, the neutron structures also highlight active site features that promote the stabilization of the transition state and slight variations in these interactions that result in 100-fold difference in binding affinities between the DADMe-ImmA and ImmA analogs.« less

Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states

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

Banco, Michael T.; Mishra, Vidhi; Ostermann, Andreas

MTAN (5'-methylthioadenosine nucleosidase) catalyzes the hydrolysis of the N-ribosidic bond of a variety of adenosine-containing metabolites. The Helicobacter pylori MTAN (HpMTAN) hydrolyzes 6-amino-6-deoxyfutalosine in the second step of the alternative menaquinone biosynthetic pathway. Substrate binding of the adenine moiety is mediated almost exclusively by hydrogen bonds, and the proposed catalytic mechanism requires multiple proton-transfer events. Of particular interest is the protonation state of residue D198, which possesses a pK a above 8 and functions as a general acid to initiate the enzymatic reaction. In this study we present three corefined neutron/X-ray crystal structures of wild-type HpMTAN cocrystallized with S-adenosylhomocysteine (SAH),more » Formycin A (FMA), and (3R,4S)-4-(4-Chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine (p-ClPh-Thio-DADMe-ImmA) as well as one neutron/X-ray crystal structure of an inactive variant (HpMTAN-D198N) cocrystallized with SAH. These results support a mechanism of D198 pKa elevation through the unexpected sharing of a proton with atom N7 of the adenine moiety possessing unconventional hydrogen-bond geometry. Additionally, the neutron structures also highlight active site features that promote the stabilization of the transition state and slight variations in these interactions that result in 100-fold difference in binding affinities between the DADMe-ImmA and ImmA analogs.« less

Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states

DOE PAGES

Banco, Michael T.; Mishra, Vidhi; Ostermann, Andreas; ...

2016-10-01

MTAN (5'-methylthioadenosine nucleosidase) catalyzes the hydrolysis of the N-ribosidic bond of a variety of adenosine-containing metabolites. The Helicobacter pylori MTAN (HpMTAN) hydrolyzes 6-amino-6-deoxyfutalosine in the second step of the alternative menaquinone biosynthetic pathway. Substrate binding of the adenine moiety is mediated almost exclusively by hydrogen bonds, and the proposed catalytic mechanism requires multiple proton-transfer events. Of particular interest is the protonation state of residue D198, which possesses a pK a above 8 and functions as a general acid to initiate the enzymatic reaction. In this study we present three corefined neutron/X-ray crystal structures of wild-type HpMTAN cocrystallized with S-adenosylhomocysteine (SAH),more » Formycin A (FMA), and (3R,4S)-4-(4-Chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine (p-ClPh-Thio-DADMe-ImmA) as well as one neutron/X-ray crystal structure of an inactive variant (HpMTAN-D198N) cocrystallized with SAH. These results support a mechanism of D198 pKa elevation through the unexpected sharing of a proton with atom N7 of the adenine moiety possessing unconventional hydrogen-bond geometry. Additionally, the neutron structures also highlight active site features that promote the stabilization of the transition state and slight variations in these interactions that result in 100-fold difference in binding affinities between the DADMe-ImmA and ImmA analogs.« less

Neuronal plasticity and multisensory integration in filial imprinting.

PubMed

Town, Stephen Michael; McCabe, Brian John

2011-03-10

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus.

Neuronal Plasticity and Multisensory Integration in Filial Imprinting

PubMed Central

Town, Stephen Michael; McCabe, Brian John

2011-01-01

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus. PMID:21423770

Preparation, Separation, and Conformational Analysis of Differentially Sulfated Heparin Octasaccharide Isomers using Ion Mobility Mass Spectrometry

PubMed Central

Seo, Youjin; Andaya, Armann; Leary, Julie A.

2012-01-01

Heparin is a linear sulfated polysaccharide widely used in medicine because of its anticoagulant properties. The various sulfation and/or acetylation patterns on heparin impart different degrees of conformational change around the glycosidic bonds and subsequently alter its function as an anticoagulant, anticancer, or antiviral drug. Characterization of these structures is important for eventual elucidation of its function but presents itself as an analytical challenge due to the inherent heterogeneity of the carbohydrates. Heparin octasaccharide structural isomers of various sulfation patterns were investigated using ion mobility mass spectrometry (IMMS). In addition to distinguishing the isomers, we report the preparation and tandem mass spectrometry analysis for multiple sulfated or acetylated oligosaccharides. Herein, our data indicate that heparin octasaccharide isomers were separated based on their structural conformations in the ion mobility cell. Subsequent to this separation, isomers were further distinguished using product ions resulting from tandem mass spectrometry. Overall, IMMS analysis was used to successfully characterize and separate individual isomers and subsequently measure their conformations. PMID:22283665

Effects of drift gas on collision cross sections of a protein standard in linear drift tube and traveling wave ion mobility mass spectrometry.

PubMed

Jurneczko, Ewa; Kalapothakis, Jason; Campuzano, Iain D G; Morris, Michael; Barran, Perdita E

2012-10-16

There has been a significant increase in the use of ion mobility mass spectrometry (IM-MS) to investigate conformations of proteins and protein complexes following electrospray ionization. Investigations which employ traveling wave ion mobility mass spectrometry (TW IM-MS) instrumentation rely on the use of calibrants to convert the arrival times of ions to collision cross sections (CCS) providing "hard numbers" of use to structural biology. It is common to use nitrogen as the buffer gas in TW IM-MS instruments and to calibrate by extrapolating from CCS measured in helium via drift tube (DT) IM-MS. In this work, both DT and TW IM-MS instruments are used to investigate the effects of different drift gases (helium, neon, nitrogen, and argon) on the transport of multiply charged ions of the protein myoglobin, frequently used as a standard in TW IM-MS studies. Irrespective of the drift gas used, recorded mass spectra are found to be highly similar. In contrast, the recorded arrival time distributions and the derived CCS differ greatly. At low charge states (7 ≤ z ≤ 11) where the protein is compact, the CCS scale with the polarizability of the gas; this is also the case for higher charge states (12 ≤ z ≤ 22) where the protein is more unfolded for the heavy gases (neon, argon, and nitrogen) but not the case for helium. This is here interpreted as a different conformational landscape being sampled by the lighter gas and potentially attributable to increased field heating by helium. Under nanoelectrospray ionization (nESI) conditions, where myoglobin is sprayed from an aqueous solution buffered to pH 6.8 with 20 mM ammonium acetate, in the DT IM-MS instrument, each buffer gas can yield a different arrival time distribution (ATD) for any given charge state.

The Integrated Medical Model: A Probabilistic Simulation Model for Predicting In-Flight Medical Risks

NASA Technical Reports Server (NTRS)

Keenan, Alexandra; Young, Millennia; Saile, Lynn; Boley, Lynn; Walton, Marlei; Kerstman, Eric; Shah, Ronak; Goodenow, Debra A.; Myers, Jerry G.

2015-01-01

The Integrated Medical Model (IMM) is a probabilistic model that uses simulation to predict mission medical risk. Given a specific mission and crew scenario, medical events are simulated using Monte Carlo methodology to provide estimates of resource utilization, probability of evacuation, probability of loss of crew, and the amount of mission time lost due to illness. Mission and crew scenarios are defined by mission length, extravehicular activity (EVA) schedule, and crew characteristics including: sex, coronary artery calcium score, contacts, dental crowns, history of abdominal surgery, and EVA eligibility. The Integrated Medical Evidence Database (iMED) houses the model inputs for one hundred medical conditions using in-flight, analog, and terrestrial medical data. Inputs include incidence, event durations, resource utilization, and crew functional impairment. Severity of conditions is addressed by defining statistical distributions on the dichotomized best and worst-case scenarios for each condition. The outcome distributions for conditions are bounded by the treatment extremes of the fully treated scenario in which all required resources are available and the untreated scenario in which no required resources are available. Upon occurrence of a simulated medical event, treatment availability is assessed, and outcomes are generated depending on the status of the affected crewmember at the time of onset, including any pre-existing functional impairments or ongoing treatment of concurrent conditions. The main IMM outcomes, including probability of evacuation and loss of crew life, time lost due to medical events, and resource utilization, are useful in informing mission planning decisions. To date, the IMM has been used to assess mission-specific risks with and without certain crewmember characteristics, to determine the impact of eliminating certain resources from the mission medical kit, and to design medical kits that maximally benefit crew health while meeting mass and volume constraints.

The Integrated Medical Model: A Probabilistic Simulation Model Predicting In-Flight Medical Risks

NASA Technical Reports Server (NTRS)

Keenan, Alexandra; Young, Millennia; Saile, Lynn; Boley, Lynn; Walton, Marlei; Kerstman, Eric; Shah, Ronak; Goodenow, Debra A.; Myers, Jerry G., Jr.

2015-01-01

The Integrated Medical Model (IMM) is a probabilistic model that uses simulation to predict mission medical risk. Given a specific mission and crew scenario, medical events are simulated using Monte Carlo methodology to provide estimates of resource utilization, probability of evacuation, probability of loss of crew, and the amount of mission time lost due to illness. Mission and crew scenarios are defined by mission length, extravehicular activity (EVA) schedule, and crew characteristics including: sex, coronary artery calcium score, contacts, dental crowns, history of abdominal surgery, and EVA eligibility. The Integrated Medical Evidence Database (iMED) houses the model inputs for one hundred medical conditions using in-flight, analog, and terrestrial medical data. Inputs include incidence, event durations, resource utilization, and crew functional impairment. Severity of conditions is addressed by defining statistical distributions on the dichotomized best and worst-case scenarios for each condition. The outcome distributions for conditions are bounded by the treatment extremes of the fully treated scenario in which all required resources are available and the untreated scenario in which no required resources are available. Upon occurrence of a simulated medical event, treatment availability is assessed, and outcomes are generated depending on the status of the affected crewmember at the time of onset, including any pre-existing functional impairments or ongoing treatment of concurrent conditions. The main IMM outcomes, including probability of evacuation and loss of crew life, time lost due to medical events, and resource utilization, are useful in informing mission planning decisions. To date, the IMM has been used to assess mission-specific risks with and without certain crewmember characteristics, to determine the impact of eliminating certain resources from the mission medical kit, and to design medical kits that maximally benefit crew health while meeting mass and volume constraints.

Discrimination of Native-like States of Membrane Proteins with Implicit Membrane-based Scoring Functions.

PubMed

Dutagaci, Bercem; Wittayanarakul, Kitiyaporn; Mori, Takaharu; Feig, Michael

2017-06-13

A scoring protocol based on implicit membrane-based scoring functions and a new protocol for optimizing the positioning of proteins inside the membrane was evaluated for its capacity to discriminate native-like states from misfolded decoys. A decoy set previously established by the Baker lab (Proteins: Struct., Funct., Genet. 2006, 62, 1010-1025) was used along with a second set that was generated to cover higher resolution models. The Implicit Membrane Model 1 (IMM1), IMM1 model with CHARMM 36 parameters (IMM1-p36), generalized Born with simple switching (GBSW), and heterogeneous dielectric generalized Born versions 2 (HDGBv2) and 3 (HDGBv3) were tested along with the new HDGB van der Waals (HDGBvdW) model that adds implicit van der Waals contributions to the solvation free energy. For comparison, scores were also calculated with the distance-scaled finite ideal-gas reference (DFIRE) scoring function. Z-scores for native state discrimination, energy vs root-mean-square deviation (RMSD) correlations, and the ability to select the most native-like structures as top-scoring decoys were evaluated to assess the performance of the scoring functions. Ranking of the decoys in the Baker set that were relatively far from the native state was challenging and dominated largely by packing interactions that were captured best by DFIRE with less benefit of the implicit membrane-based models. Accounting for the membrane environment was much more important in the second decoy set where especially the HDGB-based scoring functions performed very well in ranking decoys and providing significant correlations between scores and RMSD, which shows promise for improving membrane protein structure prediction and refinement applications. The new membrane structure scoring protocol was implemented in the MEMScore web server ( http://feiglab.org/memscore ).

Consistency of immigrant and country-of-birth suicide rates: a meta-analysis.

PubMed

Voracek, M; Loibl, L M

2008-10-01

Multifaceted evidence (family, twin, adoption, molecular genetic, geographic and surname studies of suicide) suggests genetic risk factors for suicide. Migrant studies are also informative in this context, but underused. In particular, a meta-analysis of the associations of immigrant (IMM) and country-of-birth (COB) suicide rates is unavailable. Thirty-three studies, reporting IMM suicide rates for nearly 50 nationalities in seven host countries (Australia, Austria, Canada, England, the Netherlands, Sweden and the USA), were retrieved. Total-population IMM and COB suicide rates were strongly positively associated (combined rank-order correlation across 20 eligible studies: 0.65, 95% CI: 0.56-0.73, P < 10(-9)). The effect generalized across both sexes, host countries and study periods. Following the logic of the migrant study design of genetic epidemiology, the correspondence of IMM and COB suicide rates is consistent with the assumption of population differences in the prevalence of genetic risk factors for suicide.

High Radiation Resistance IMM Solar Cell

NASA Technical Reports Server (NTRS)

Pan, Noren

2015-01-01

Due to high launch costs, weight reduction is a key driver for the development of new solar cell technologies suitable for space applications. This project is developing a unique triple-junction inverted metamorphic multijunction (IMM) technology that enables the manufacture of very lightweight, low-cost InGaAsP-based multijunction solar cells. This IMM technology consists of indium (In) and phosphorous (P) solar cell active materials, which are designed to improve the radiation-resistant properties of the triple-junction solar cell while maintaining high efficiency. The intrinsic radiation hardness of InP materials makes them of great interest for building solar cells suitable for deployment in harsh radiation environments, such as medium Earth orbit and missions to the outer planets. NASA Glenn's recently developed epitaxial lift-off (ELO) process also will be applied to this new structure, which will enable the fabrication of the IMM structure without the substrate.

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes.

PubMed

Sachdev, Saachi; Wang, Qi; Billington, Charles; Connett, John; Ahmed, Leaque; Inabnet, William; Chua, Streamson; Ikramuddin, Sayeed; Korner, Judith

2016-05-01

This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n = 15) or RYGB (n = 15). Mean HbA1c decreased from 9.7 to 6.4% after RYGB and from 9.1 to 6.1% in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB, FGF19 increased in the fasted (93 ± 15 to 152 ± 19 pg/ml; P = 0.008) and postprandial states (area under the curve (AUC), 10.8 ± 1.9 to 23.4 ± 4.1 pg × h/ml × 10(3); P = 0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC ×10(3), 6.63 ± 1.3 to 15.16 ± 2.56 μM × h; P = 0.003) and decreased after IMM (AUC ×10(3), 8.22 ± 1.24 to 5.70 ± 0.70; P = 0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r = 0.54, P = 0.04) and trended negatively with HbA1c (r = -0.44; P = 0.09); these associations were not observed after IMM. BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

Roux-en-Y Gastric Bypass versus Intensive Medical Management for the Control of Type 2 Diabetes, Hypertension and Hyperlipidemia: An International, Multicenter, Randomized Trial

PubMed Central

Ikramuddin, Sayeed; Korner, Judith; Lee, Wei-Jei; Connett, John E.; Inabnet, William B.; Billington, Charles B.; Thomas, Avis J.; Leslie, Daniel B.; Chong, Keong; Jeffery, Robert W.; Ahmed, Leaque; Vella, Adrian; Chuang, Lee-Ming; Bessler, Marc; Sarr, Michael G.; Swain, James M.; Laqua, Patricia; Jensen, Michael D.; Bantle, John P.

2014-01-01

Context Guideline directed care for diabetes calls for control of glycemia, blood pressure and cholesterol (composite goal). Most patients treated medically do not reach this goal. Objective Determine the efficacy and safety of Roux-en-Y gastric bypass (RYGB) added to lifestyle modification and intensive medical management (LS/IMM) to achieve control of all 3 endpoints. Design Two-arm unblinded randomized clinical trial with 120 participants. The primary endpoint of the composite outcome was assessed at 12 months. The study began in April 2008 and completed one year follow-up in all participants in December 2012. Setting Four academic teaching hospitals in the U.S. and Taiwan, involving five operating surgeons. Participants Inclusion criteria for the Diabetes Surgery Study (DSS) included HbA1c ≥ 8.0%, BMI 30.0-39.9 kg/m2, diagnosis and treatment of type 2 diabetes for at least six months, and stimulated C peptide > 1.0 ng/ml. Interventions All patients received lifestyle intervention modeled after the Look AHEAD study. Medications for hyperglycemia, hypertension, and dyslipidemia were prescribed according to protocol. RYGB techniques were standardized. Main Outcome Measure Attainment of a composite goal: HbA1c < 7.0%, LDL-C < 100 mg/dl, and SBP < 130 mmHg. Results One hundred and twenty participants were randomized with equal probability into LS/IMM or RYGB (60 in each group). Baseline characteristics were similar between groups. Mean BMI was 34.6 kg/m2 (95% CI 29.2 to 40.8 kg/m2) with 71 (59%; 95% CI 50% to 68%) participants having BMI < 35 kg/m2, and mean HbA1c was 9.6% (95% CI 9.4% to 9.8%). At 12 months the followup rate was 95%, and 11 (19%) in the LS/IMM group and 28 (49%) in the RYGB group achieved the primary endpoint (OR = 4.8, 95% CI 1.9 to 11.6). RYGB participants required 3.1 fewer medications than LS/IMM (4.8 versus 1.7, 95% CI -3.6 to -2.3). Weight loss was 7.9% LS/IMM vs. 26.1% RYGB (difference 18.2% 95% CI 14.2% to 20.7%). Regression analyses indicate that achieving the composite endpoint was primarily attributable to weight loss. There were 22 serious adverse events in the RYGB group, including one cardiovascular event, and 15 in the LS/IMM group. There were 4 peri-operative complications and 6 late postoperative complications in the RYGB group. Nutritional deficiency of iron, vitamin B12 and albumin were observed more frequently with RYGB. Conclusions In mild to moderately obese patients with type 2 diabetes addition of RYGB to LS/IMM resulted in greater likelihood of achieving the composite treatment goal. RYGB participants required fewer medications but had more complications. PMID:23736733

Estimating the Risk of Renal Stone Events during Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Reyes, David; Kerstman, Eric; Gray, Gary; Locke, James

2014-01-01

Introduction: Given the bone loss and increased urinary calcium excretion in the microgravity environment, persons participating in long-duration spaceflight may have an increased risk for renal stone formation. Renal stones are often an incidental finding of abdominal imaging studies done for other reasons. Thus, some crewmembers may have undiscovered, asymptomatic stones prior to their mission. Methods: An extensive literature search was conducted concerning the natural history of asymptomatic renal stones. For comparison, simulations were done using the Integrated Medical Model (IMM). The IMM is an evidence-based decision support tool that provides risk analysis and has the capability to optimize medical systems for missions by minimizing the occurrence of adverse mission outcomes such as evacuation and loss of crew life within specified mass and volume constraints. Results: The literature of the natural history of asymptomatic renal stones in the general medical population shows that the probability of symptomatic event is 8% to 34% at 1 to 3 years for stones < 7 mm. Extrapolated to a 6-month mission, for stones < 5 to 7 mm, the risk for any stone event is about 4 to 6%, with a 0.7% to 4% risk for intervention, respectively. IMM simulations compare favorably with risk estimates garnered from the terrestrial literature. The IMM forecasts that symptomatic renal stones may be one of the top drivers for medical evacuation of an International Space Station (ISS) mission. Discussion: Although the likelihood of a stone event is low, the consequences could be severe due to limitations of current ISS medical capabilities. Therefore, these risks need to be quantified to aid planning, limit crew morbidity and mitigate mission impacts. This will be especially critical for missions beyond earth orbit, where evacuation may not be an option.

Estimating the Risk of Renal Stone Events During Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Reyes, David; Kerstman, Eric; Locke, James

2014-01-01

Introduction: Given the bone loss and increased urinary calcium excretion in the microgravity environment, persons participating in long-duration spaceflight may have an increased risk for renal stone formation. Renal stones are often an incidental finding of abdominal imaging studies done for other reasons. Thus, some crewmembers may have undiscovered, asymptomatic stones prior to their mission. Methods: An extensive literature search was conducted concerning the natural history of asymptomatic renal stones. For comparison, simulations were done using the Integrated Medical Model (IMM). The IMM is an evidence-based decision support tool that provides risk analysis and has the capability to optimize medical systems for missions by minimizing the occurrence of adverse mission outcomes such as evacuation and loss of crew life within specified mass and volume constraints. Results: The literature of the natural history of asymptomatic renal stones in the general medical population shows that the probability of symptomatic event is 8% to 34% at 1 to 3 years for stones < 7 mm. Extrapolated to a 6-month mission, for stones < 5 to 7 mm, the risk for any stone event is about 4 to 6%, with a 0.7% to 4% risk for intervention, respectively. IMM simulations compare favorably with risk estimates garnered from the terrestrial literature. The IMM forecasts that symptomatic renal stones may be one of the top drivers for medical evacuation of an International Space Station (ISS) mission. Discussion: Although the likelihood of a stone event is low, the consequences could be severe due to limitations of current ISS medical capabilities. Therefore, these risks need to be quantified to aid planning, limit crew morbidity and mitigate mission impacts. This will be especially critical for missions beyond earth orbit, where evacuation may not be an option.

Comparison of Different Ion Mobility Setups Using Poly (Ethylene Oxide) PEO Polymers: Drift Tube, TIMS, and T-Wave

NASA Astrophysics Data System (ADS)

Haler, Jean R. N.; Massonnet, Philippe; Chirot, Fabien; Kune, Christopher; Comby-Zerbino, Clothilde; Jordens, Jan; Honing, Maarten; Mengerink, Ynze; Far, Johann; Dugourd, Philippe; De Pauw, Edwin

2018-01-01

Over the years, polymer analyses using ion mobility-mass spectrometry (IM-MS) measurements have been performed on different ion mobility spectrometry (IMS) setups. In order to be able to compare literature data taken on different IM(-MS) instruments, ion heating and ion temperature evaluations have already been explored. Nevertheless, extrapolations to other analytes are difficult and thus straightforward same-sample instrument comparisons seem to be the only reliable way to make sure that the different IM(-MS) setups do not greatly change the gas-phase behavior. We used a large range of degrees of polymerization (DP) of poly(ethylene oxide) PEO homopolymers to measure IMS drift times on three different IM-MS setups: a homemade drift tube (DT), a trapped (TIMS), and a traveling wave (T-Wave) IMS setup. The drift time evolutions were followed for increasing polymer DPs (masses) and charge states, and they are found to be comparable and reproducible on the three instruments. [Figure not available: see fulltext.

48 CFR 208.7003-1 - Assignments under integrated materiel management (IMM).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Assignments under integrated materiel management (IMM). 208.7003-1 Section 208.7003-1 Federal Acquisition Regulations System... SUPPLIES AND SERVICES Coordinated Acquisition 208.7003-1 Assignments under integrated materiel management...

48 CFR 208.7003-1 - Assignments under integrated materiel management (IMM).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Assignments under integrated materiel management (IMM). 208.7003-1 Section 208.7003-1 Federal Acquisition Regulations System... SUPPLIES AND SERVICES Coordinated Acquisition 208.7003-1 Assignments under integrated materiel management...

48 CFR 208.7003-1 - Assignments under integrated materiel management (IMM).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Assignments under integrated materiel management (IMM). 208.7003-1 Section 208.7003-1 Federal Acquisition Regulations System... SUPPLIES AND SERVICES Coordinated Acquisition 208.7003-1 Assignments under integrated materiel management...

48 CFR 208.7003-1 - Assignments under integrated materiel management (IMM).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Assignments under integrated materiel management (IMM). 208.7003-1 Section 208.7003-1 Federal Acquisition Regulations System... SUPPLIES AND SERVICES Coordinated Acquisition 208.7003-1 Assignments under integrated materiel management...

48 CFR 208.7003-1 - Assignments under integrated materiel management (IMM).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Assignments under integrated materiel management (IMM). 208.7003-1 Section 208.7003-1 Federal Acquisition Regulations System... SUPPLIES AND SERVICES Coordinated Acquisition 208.7003-1 Assignments under integrated materiel management...

Clinical evaluation of a Mucorales-specific real-time PCR assay in tissue and serum samples.

PubMed

Springer, Jan; Lackner, Michaela; Ensinger, Christian; Risslegger, Brigitte; Morton, Charles Oliver; Nachbaur, David; Lass-Flörl, Cornelia; Einsele, Hermann; Heinz, Werner J; Loeffler, Juergen

2016-12-01

Molecular diagnostic assays can accelerate the diagnosis of fungal infections and subsequently improve patient outcomes. In particular, the detection of infections due to Mucorales is still challenging for laboratories and physicians. The aim of this study was to evaluate a probe-based Mucorales-specific real-time PCR assay (Muc18S) using tissue and serum samples from patients suffering from invasive mucormycosis (IMM). This assay can detect a broad range of clinically relevant Mucorales species and can be used to complement existing diagnostic tests or to screen high-risk patients. An advantage of the Muc18S assay is that it exclusively detects Mucorales species allowing the diagnosis of Mucorales DNA without sequencing within a few hours. In paraffin-embedded tissue samples this PCR-based method allowed rapid identification of Mucorales in comparison with standard methods and showed 91 % sensitivity in the IMM tissue samples. We also evaluated serum samples, an easily accessible material, from patients at risk from IMM. Mucorales DNA was detected in all patients with probable/proven IMM (100 %) and in 29 % of the possible cases. Detection of IMM in serum could enable an earlier diagnosis (up to 21 days) than current methods including tissue samples, which were gained mainly post-mortem. A screening strategy for high-risk patients, which would enable targeted treatment to improve patient outcomes, is therefore possible.

Broadband ion mobility deconvolution for rapid analysis of complex mixtures.

PubMed

Pettit, Michael E; Brantley, Matthew R; Donnarumma, Fabrizio; Murray, Kermit K; Solouki, Touradj

2018-05-04

High resolving power ion mobility (IM) allows for accurate characterization of complex mixtures in high-throughput IM mass spectrometry (IM-MS) experiments. We previously demonstrated that pure component IM-MS data can be extracted from IM unresolved post-IM/collision-induced dissociation (CID) MS data using automated ion mobility deconvolution (AIMD) software [Matthew Brantley, Behrooz Zekavat, Brett Harper, Rachel Mason, and Touradj Solouki, J. Am. Soc. Mass Spectrom., 2014, 25, 1810-1819]. In our previous reports, we utilized a quadrupole ion filter for m/z-isolation of IM unresolved monoisotopic species prior to post-IM/CID MS. Here, we utilize a broadband IM-MS deconvolution strategy to remove the m/z-isolation requirement for successful deconvolution of IM unresolved peaks. Broadband data collection has throughput and multiplexing advantages; hence, elimination of the ion isolation step reduces experimental run times and thus expands the applicability of AIMD to high-throughput bottom-up proteomics. We demonstrate broadband IM-MS deconvolution of two separate and unrelated pairs of IM unresolved isomers (viz., a pair of isomeric hexapeptides and a pair of isomeric trisaccharides) in a simulated complex mixture. Moreover, we show that broadband IM-MS deconvolution improves high-throughput bottom-up characterization of a proteolytic digest of rat brain tissue. To our knowledge, this manuscript is the first to report successful deconvolution of pure component IM and MS data from an IM-assisted data-independent analysis (DIA) or HDMSE dataset.

Integrated Display and Simulation for Automatic Dependent Surveillance–Broadcast and Traffic Collision Avoidance System Data Fusion

PubMed Central

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-01-01

Automatic Dependent Surveillance–Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications. PMID:29137194

Using Interactive Multimedia to Teach Pedestrian Safety: An Exploratory Study

ERIC Educational Resources Information Center

Glang, Ann; Noell, John; Ary, Dennis; Swartz, Lynne

2005-01-01

Objectives: To evaluate an interactive multimedia (IMM) program that teaches young children safe pedestrian skills. Methods: The program uses IMM (animation and video) to teach children critical skills for crossing streets safely. A computer-delivered video assessment and a real-life street simulation were used to measure the effectiveness of the…

Food safety education using an interactive multimedia kiosk in a WIC setting: correlates of client satisfaction and practical issues.

PubMed

Trepka, Mary Jo; Newman, Frederick L; Huffman, Fatma G; Dixon, Zisca

2010-01-01

To assess acceptability of food safety education delivered by interactive multimedia (IMM) in a Supplemental Nutrition Program for Women, Infants and Children Program (WIC) clinic. Female clients or caregivers (n=176) completed the food-handling survey; then an IMM food safety education program on a computer kiosk. Satisfaction with program, participant demographics, and change in food-handling behavior were assessed by univariate analyses. Over 90% of the participants enjoyed the kiosk, and most (87.5%) reported using computers a lot. Compared with participants with education beyond high school, participants with less education were more likely to report enjoying the kiosk (98.2% vs 88.1%, P = .007), preferred learning with the kiosk (91.7% vs 79.1%, P = .02), and would like to learn about other topics using IMM (95.4% vs 86.6%, P = .04). Food safety education delivered by IMM was well accepted by inner-city WIC clinic clients, including those with less education. Copyright 2010 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

Fingernail Injuries and NASA's Integrated Medical Model

NASA Technical Reports Server (NTRS)

Kerstman, Eric; Butler, Doug

2008-01-01

The goal of space medicine is to optimize both crew health and performance. Currently, expert opinion is primarily relied upon for decision-making regarding medical equipment and supplies flown in space. Evidence-based decisions are preferred due to mass and volume limitations and the expense of space flight. The Integrated Medical Model (IMM) is an attempt to move us in that direction!

Best cost-effectiveness and worker productivity with initial triple DMARD therapy compared with methotrexate monotherapy in early rheumatoid arthritis: cost-utility analysis of the tREACH trial.

PubMed

de Jong, Pascal H P; Hazes, Johanna M; Buisman, Leander R; Barendregt, Pieternella J; van Zeben, Derkjen; van der Lubbe, Peter A; Gerards, Andreas H; de Jager, Mike H; de Sonnaville, Peter B J; Grillet, Bernard A; Luime, Jolanda J; Weel, Angelique E A M

2016-12-01

To evaluate direct and indirect costs per quality adjusted life year (QALY) for different initial treatment strategies in very early RA. The 1-year data of the treatment in the Rotterdam Early Arthritis Cohort trial were used. Patients with a high probability (>70%) according to their likelihood of progressing to persistent arthritis, based on the prediction model of Visser, were randomized into one of following initial treatment strategies: (A) initial triple DMARD therapy (iTDT) with glucocorticoids (GCs) intramuscular (n = 91); (B) iTDT with an oral GC tapering scheme (n = 93); and (C) initial MTX monotherapy (iMM) with GCs similar to B (n = 97). Data on QALYs, measured with the Dutch EuroQol, and direct and indirect cost were used. Direct costs are costs of treatment and medical consumption, whereas indirect costs are costs due to loss of productivity. Average QALYs (sd) for A, B and C were, respectively, 0.75 (0.12), 0.75 (0.10) and 0.73 (0.13) for Dutch EuroQol. Highest total costs per QALY (sd) were, respectively, €12748 (€18767), €10 380 (€15 608) and €17 408 (€21 828) for strategy A, B and C (P = 0.012, B vs C). Direct as well as indirect costs were higher with iMM (strategy C) compared with iTDT (strategy B). Higher direct costs were due to ∼40% more biologic usage over time. Higher indirect costs, on the other hand, were caused by more long-term sickness and reduction in contract hours. iTDT was >95% cost-effective across all willingness-to-pay thresholds compared with iMM. iTDT was more cost-effective and had better worker productivity compared with iMM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improving the Effectiveness of Penicillin Allergy De-labeling.

PubMed

Bourke, Jack; Pavlos, Rebecca; James, Ian; Phillips, Elizabeth

2015-01-01

Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs. We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies. Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes. SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (≤ 1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to ≥ 1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P < .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up. Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Inner Mitochondrial Membrane Disruption Links Apoptotic and Agonist-Initiated Phosphatidylserine Externalization in Platelets.

PubMed

Choo, Hyo-Jung; Kholmukhamedov, Andaleb; Zhou, ChengZing; Jobe, Shawn

2017-08-01

Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption. In both ABT-737 (apoptotic) and agonist (necrotic)-treated platelets, phosphatidylserine externalization was temporally correlated with IMM disruption. Agonist stimulation resulted in rapid cyclophilin D-dependent IMM disruption that coincided with phosphatidylserine exposure. ABT-737 treatment caused rapid cytochrome c release, eventually followed by caspase-dependent IMM disruption that again closely coincided with phosphatidylserine exposure. A nonmitochondrial and integrin-mediated mechanism has been implicated in the formation of a novel phosphatidylserine-externalizing platelet subpopulation. Using image cytometry, this subpopulation is demonstrated to be the result of the interaction of an aggregatory platelet and a procoagulant platelet rather than indicative of a novel intracellular mechanism regulating platelet phosphatidylserine externalization. Using electron microscopy, similar interactions between aggregatory and procoagulant platelets are demonstrated in vitro and in vivo within a mesenteric vein hemostatic thrombus. Platelet phosphatidylserine externalization is closely associated with the mitochondrial event of IMM disruption identifying a common pathway in phosphatidylserine-externalizing platelets. The limited interaction of procoagulant platelets and integrin-active aggregatory platelets identifies a potential mechanism for procoagulant platelet retention within the hemostatic thrombus. © 2017 American Heart Association, Inc.

Estimating the Need for Medical Intervention due to Sleep Disruption on the International Space Station

NASA Technical Reports Server (NTRS)

Myers, Jerry G.; Lewandowski, Beth E.; Brooker, John E.; Hurst, S. R.; Mallis, Melissa M.; Caldwell, J. Lynn

2008-01-01

During ISS and shuttle missions, difficulties with sleep affect more than half of all US crews. Mitigation strategies to help astronauts cope with the challenges of disrupted sleep patterns can negatively impact both mission planning and vehicle design. The methods for addressing known detrimental impacts for some mission scenarios may have a substantial impact on vehicle specific consumable mass or volume or on the mission timeline. As part of the Integrated Medical Model (IMM) task, NASA Glenn Research Center is leading the development of a Monte Carlo based forecasting tool designed to determine the consumables required to address risks related to sleep disruption. The model currently focuses on the International Space Station and uses an algorithm that assembles representative mission schedules and feeds this into a well validated model that predicts relative levels of performance, and need for sleep (SAFTE Model, IBR Inc). Correlation of the resulting output to self-diagnosed needs for hypnotics, stimulants, and other pharmaceutical countermeasures, allows prediction of pharmaceutical use and the uncertainty of the specified prediction. This paper outlines a conceptual model for determining a rate of pharmaceutical utilization that can be used in the IMM model for comparison and optimization of mitigation methods with respect to all other significant medical needs and interventions.

Food Safety Education Using an Interactive Multimedia Kiosk in a WIC Setting: Correlates of Client Satisfaction and Practical Issues

ERIC Educational Resources Information Center

Trepka, Mary Jo; Newman, Frederick L.; Huffman, Fatma G.; Dixon, Zisca

2010-01-01

Objective: To assess acceptability of food safety education delivered by interactive multimedia (IMM) in a Supplemental Nutrition Program for Women, Infants and Children Program (WIC) clinic. Methods: Female clients or caregivers (n = 176) completed the food-handling survey; then an IMM food safety education program on a computer kiosk.…

Learner Perceptions on Instructional Design of Multimedia in Learning Abstract Concepts in Science at a Distance

ERIC Educational Resources Information Center

Kulasekara, Geetha Udayangani; Jayatilleke, Buddhini Gayathri; Coomaraswamy, Uma

2011-01-01

This study was carried out to explore learner perceptions on the instructional design features of interactive multimedia (IMM), which was especially designed to support the open and distance learners studying microbiology as a part of the BSc degree programme of the Open University of Sri Lanka (OUSL). The purpose of developing this IMM was to…

Monoclonal TCR-redirected tumor cell killing.

PubMed

Liddy, Nathaniel; Bossi, Giovanna; Adams, Katherine J; Lissina, Anna; Mahon, Tara M; Hassan, Namir J; Gavarret, Jessie; Bianchi, Frayne C; Pumphrey, Nicholas J; Ladell, Kristin; Gostick, Emma; Sewell, Andrew K; Lissin, Nikolai M; Harwood, Naomi E; Molloy, Peter E; Li, Yi; Cameron, Brian J; Sami, Malkit; Baston, Emma E; Todorov, Penio T; Paston, Samantha J; Dennis, Rebecca E; Harper, Jane V; Dunn, Steve M; Ashfield, Rebecca; Johnson, Andy; McGrath, Yvonne; Plesa, Gabriela; June, Carl H; Kalos, Michael; Price, David A; Vuidepot, Annelise; Williams, Daniel D; Sutton, Deborah H; Jakobsen, Bent K

2012-06-01

T cell immunity can potentially eradicate malignant cells and lead to clinical remission in a minority of patients with cancer. In the majority of these individuals, however, there is a failure of the specific T cell receptor (TCR)–mediated immune recognition and activation process. Here we describe the engineering and characterization of new reagents termed immune-mobilizing monoclonal TCRs against cancer (ImmTACs). Four such ImmTACs, each comprising a distinct tumor-associated epitope-specific monoclonal TCR with picomolar affinity fused to a humanized cluster of differentiation 3 (CD3)-specific single-chain antibody fragment (scFv), effectively redirected T cells to kill cancer cells expressing extremely low surface epitope densities. Furthermore, these reagents potently suppressed tumor growth in vivo. Thus, ImmTACs overcome immune tolerance to cancer and represent a new approach to tumor immunotherapy.

Structure and Inhibition of Quorum Sensing Target from Streptococcus pneumoniae

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

Singh,V.; Shi, W.; Almo, S.

2006-01-01

Streptococcus pneumoniae 5'-methylthioadenosine/S-adenosylhomocysteine hydrolase (MTAN) catalyzes the hydrolytic deadenylation of its substrates to form adenine and 5-methylthioribose or S-ribosylhomocysteine (SRH). MTAN is not found in mammals but is involved in bacterial quorum sensing. MTAN gene disruption affects the growth and pathogenicity of bacteria, making it a target for antibiotic design. Kinetic isotope effects and computational studies have established a dissociative S{sub N}1 transition state for Escherichia coli MTAN, and transition state analogues resembling the transition state are powerful inhibitors of the enzyme [Singh, V., Lee, J. L., Nunez, S., Howell, P. L., and Schramm, V. L. (2005) Biochemistry 44, 11647-11659].more » The sequence of MTAN from S. pneumoniae is 40% identical to that of E. coli MTAN, but S. pneumoniae MTAN exhibits remarkably distinct kinetic and inhibitory properties. 5'-Methylthio-Immucillin-A (MT-ImmA) is a transition state analogue resembling an early S{sub N}1 transition state. It is a weak inhibitor of S. pneumoniae MTAN with a K{sub i} of 1.0 {mu}M. The X-ray structure of S. pneumoniae MTAN with MT-ImmA indicates a dimer with the methylthio group in a flexible hydrophobic pocket. Replacing the methyl group with phenyl (PhT-ImmA), tolyl (p-TolT-ImmA), or ethyl (EtT-ImmA) groups increases the affinity to give K{sub i} values of 335, 60, and 40 nM, respectively. DADMe-Immucillins are geometric and electrostatic mimics of a fully dissociated transition state and bind more tightly than Immucillins. MT-DADMe-Immucillin-A inhibits with a K{sub i} value of 24 nM, and replacing the 5'-methyl group with p-Cl-phenyl (p-Cl-PhT-DADMe-ImmA) gave a K{sub i}* value of 0.36 nM. The inhibitory potential of DADMe-Immucillins relative to the Immucillins supports a fully dissociated transition state structure for S. pneumoniae MTAN. Comparison of active site contacts in the X-ray crystal structures of E. coli and S. pneumoniae MTAN with MT-ImmA would predict equal binding, yet most analogues bind 10{sup 3}-10{sup 4}-fold more tightly to the E. coli enzyme. Catalytic site efficiency is primarily responsible for this difference since k{sub cat}/K{sub m} for S. pneumoniae MTAN is decreased 845-fold relative to that of E. coli MTAN.« less

Implicit membrane treatment of buried charged groups: application to peptide translocation across lipid bilayers.

PubMed

Lazaridis, Themis; Leveritt, John M; PeBenito, Leo

2014-09-01

The energetic cost of burying charged groups in the hydrophobic core of lipid bilayers has been controversial, with simulations giving higher estimates than certain experiments. Implicit membrane approaches are usually deemed too simplistic for this problem. Here we challenge this view. The free energy of transfer of amino acid side chains from water to the membrane center predicted by IMM1 is reasonably close to all-atom free energy calculations. The shape of the free energy profile, however, for the charged side chains needs to be modified to reflect the all-atom simulation findings (IMM1-LF). Membrane thinning is treated by combining simulations at different membrane widths with an estimate of membrane deformation free energy from elasticity theory. This approach is first tested on the voltage sensor and the isolated S4 helix of potassium channels. The voltage sensor is stably inserted in a transmembrane orientation for both the original and the modified model. The transmembrane orientation of the isolated S4 helix is unstable in the original model, but a stable local minimum in IMM1-LF, slightly higher in energy than the interfacial orientation. Peptide translocation is addressed by mapping the effective energy of the peptide as a function of vertical position and tilt angle, which allows identification of minimum energy pathways and transition states. The barriers computed for the S4 helix and other experimentally studied peptides are low enough for an observable rate. Thus, computational results and experimental studies on the membrane burial of peptide charged groups appear to be consistent. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014 Elsevier B.V. All rights reserved.

A Quantitative Risk-Benefit Analysis of Prophylactic Surgery Prior to Extended-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Carroll, Danielle; Reyes, David; Kerstman, Eric; Walton, Marlei; Antonsen, Erik

2017-01-01

INTRODUCTION: Among otherwise healthy astronauts undertaking deep space missions, the risks for acute appendicitis (AA) and cholecystitis (AC) are not zero. If these conditions were to occur during spaceflight they may require surgery for definitive care. The proposed study quantifies and compares the risks of developing de novo AA and AC in-flight to the surgical risks of prophylactic laparoscopic appendectomy (LA) and cholecystectomy (LC) using NASA's Integrated Medical Model (IMM). METHODS: The IMM is a Monte Carlo simulation that forecasts medical events during spaceflight missions and estimates the impact of these medical events on crew health. In this study, four Design Reference Missions (DRMs) were created to assess the probability of an astronaut developing in-flight small-bowel obstruction (SBO) following prophylactic 1) LA, 2) LC, 3) LA and LC, or 4) neither surgery (SR# S-20160407-351). Model inputs were drawn from a large, population-based 2011 Swedish study that examined the incidence and risks of post-operative SBO over a 5-year follow-up period. The study group included 1,152 patients who underwent LA, and 16,371 who underwent LC. RESULTS: Preliminary results indicate that prophylactic LA may yield higher mission risks than the control DRM. Complete analyses are pending and will be subsequently available. DISCUSSION: The risk versus benefits of prophylactic surgery in astronauts to decrease the probability of acute surgical events during spaceflight has only been qualitatively examined in prior studies. Within the assumptions and limitations of the IMM, this work provides the first quantitative guidance that has previously been lacking to this important question for future deep space exploration missions.

The targeted anti-oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue.

PubMed

Gottwald, Esther M; Duss, Michael; Bugarski, Milica; Haenni, Dominik; Schuh, Claus D; Landau, Ehud M; Hall, Andrew M

2018-04-01

Kidney proximal tubules (PTs) contain a high density of mitochondria, which are required to generate ATP to power solute transport. Mitochondrial dysfunction is implicated in the pathogenesis of numerous kidney diseases. Damaged mitochondria are thought to produce excess reactive oxygen species (ROS), which can lead to oxidative stress and activation of cell death pathways. MitoQ is a mitochondrial targeted anti-oxidant that has shown promise in preclinical models of renal diseases. However, recent studies in nonkidney cells have suggested that MitoQ might also have adverse effects. Here, using a live imaging approach, and both in vitro and ex vivo models, we show that MitoQ induces rapid swelling and depolarization of mitochondria in PT cells, but these effects were not observed with SS-31, another targeted anti-oxidant. MitoQ consists of a lipophilic cation (Tetraphenylphosphonium [TPP]) joined to an anti-oxidant component (quinone) by a 10-carbon alkyl chain, which is thought to insert into the inner mitochondrial membrane (IMM). We found that mitochondrial swelling and depolarization was also induced by dodecyltriphenylphosphomium (DTPP), which consists of TPP and the alkyl chain, but not by TPP alone. Surprisingly, MitoQ-induced mitochondrial swelling occurred in the absence of a decrease in oxygen consumption rate. We also found that DTPP directly increased the permeability of artificial liposomes with a cardiolipin content similar to that of the IMM. In summary, MitoQ causes mitochondrial swelling and depolarization in PT cells by a mechanism unrelated to anti-oxidant activity, most likely because of increased IMM permeability due to insertion of the alkyl chain. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Treatments of clinical mastitis occurring in cows on 51 large dairy herds in Wisconsin.

PubMed

Oliveira, L; Ruegg, P L

2014-09-01

Antimicrobials are frequently used for treatment of bovine mastitis and few studies have examined modern treatment strategies on large US dairy farms. The objective of this study was to describe treatment practices for clinical mastitis occurring in cows on large dairy herds in Wisconsin. Treatments performed on 747 cows experiencing cases of mild, moderate, or severe symptoms of clinical mastitis were recorded on 51 Wisconsin dairy farms. Duplicate milk samples were collected from the affected quarter for microbiological analysis at the onset of clinical mastitis and 14 to 21 d after treatment ended. Cows were treated according to individual farm protocol. Drugs and doses used for treatments were recorded for each case. Among all herds, 5 intramammary (IMM) antimicrobials (amoxicillin, hetacillin, pirlimycin, ceftiofur, and cephapirin) were used to treat cows for clinical mastitis. Of 712 cows with complete treatment data, 71.6% were treated with IMM ceftiofur either solely or combined with other antimicrobials (administered either IMM or systemically). Of cows experiencing severe symptoms of clinical mastitis, 43.8% received IMM treatment concurrent with systemic antimicrobials. Of all cows treated, 23.1% received an additional secondary treatment (either IMM, systemic, or both) because of perceived lack of response to the initial treatment. The majority of IMM treatments were administered to cows with a microbiological diagnosis of no growth (34.9%) or Escherichia coli (27.2%). Half of the cows experiencing cases caused by E. coli were treated using systemic antimicrobials in contrast to only 6.8% of cows experiencing cases caused by coagulase-negative staphylococci. In conflict with FDA regulations, which do not allow extra-label treatments using sulfonamides, a total of 22 cows from 8 farms were treated with systemic sulfadimethoxine either solely or in combination with oxytetracycline. Antimicrobial drugs were used on all herds and many cows received extra-label treatments. Great opportunity exists to improve mastitis therapy on large dairy herds, but use of more diagnostic methodologies is necessary to guide treatments. Farmers and veterinarians should work together to create protocols based on the herd needs considering reduced inappropriate and excessive use of antimicrobials. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Anopheles gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure, and Inhibition

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

Taylor,E.; Rinaldo-Matthis, A.; Li, L.

The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast formore » AgPNP at 226 s-1 for guanosine in pre-steady-state studies. 5'-Deaza-1'-aza-2'-deoxy-1'-(9-methylene)-Immucillin-H (DADMe-ImmH) is a transition-state mimic for a 2'-deoxyinosine ribocation with a fully dissociated N-ribosidic bond and is a slow-onset, tight-binding inhibitor with a dissociation constant of 3.5 pM. This is the tightest-binding inhibitor known for any PNP, with a remarkable Km/Ki* of 5.4 x 107, and is consistent with enzymatic transition state predictions of enhanced transition-state analogue binding in enzymes with enhanced catalytic efficiency. Deoxyguanosine is a weaker substrate than deoxyinosine, and DADMe-Immucillin-G is less tightly bound than DADMe-ImmH, with a dissociation constant of 23 pM for AgPNP as compared to 7 pM for HsPNP. The crystal structure of AgPNP was determined in complex with DADMe-ImmH and phosphate to a resolution of 2.2 Angstroms to reveal the differences in substrate and inhibitor specificity. The distance from the N1' cation to the phosphate O4 anion is shorter in the AgPNP{center_dot}DADMe-ImmH{center_dot}PO4 complex than in HsPNP{center_dot}DADMe-ImmH{center_dot}SO4, offering one explanation for the stronger inhibitory effect of DADMe-ImmH for AgPNP.« less

Differential Toxicity of mDia Formin-Directed Functional Agonists and Antagonists in Developing Zebrafish.

PubMed

LeCorgne, Hunter; Tudosie, Andrew M; Lavik, Kari; Su, Robin; Becker, Kathryn N; Moore, Sara; Walia, Yashna; Wisner, Alexander; Koehler, Daniel; Alberts, Arthur S; Williams, Frederick E; Eisenmann, Kathryn M

2018-01-01

The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants. mDia formin activation with small molecule intramimics IMM01/02 and mDia2-DAD peptides inhibited glioblastoma motility and invasion in vitro and ex vivo rat brain slices. However, SMIFH2, IMMs, and mDia2 DAD efficacy in vivo remains largely unexplored and potential toxicity across a range of developmental phenotypes has not been thoroughly characterized. In this study, we performed an in vivo screen of early life-stage toxicity in Danio rerio zebrafish embryos 2 days post-fertilization (dpf) in response to SMIFH2, IMM01/02, and mDia2 DAD. SMIFH2 at concentrations ≥5-10 μM induced significant defects in developing zebrafish, including shorter body lengths, tail curvature and defective tail cellularity, craniofacial malformations, pericardial edema, absent and/or compromised vasculature function and flow, depressed heart rates and increased mortality. Conversely, IMM and mDia2 DAD peptides were minimally toxic at concentrations up to 10-20 and 50 μM, respectively. SMIFH2's therapeutic potential may therefore be limited by its substantial in vivo toxicity at functional concentrations. mDia formin agonism with IMMs and mDia2 DADs may therefore be a more effective and less toxic anti-invasive therapeutic approach.

Differential Toxicity of mDia Formin-Directed Functional Agonists and Antagonists in Developing Zebrafish

PubMed Central

LeCorgne, Hunter; Tudosie, Andrew M.; Lavik, Kari; Su, Robin; Becker, Kathryn N.; Moore, Sara; Walia, Yashna; Wisner, Alexander; Koehler, Daniel; Alberts, Arthur S.; Williams, Frederick E.; Eisenmann, Kathryn M.

2018-01-01

The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants. mDia formin activation with small molecule intramimics IMM01/02 and mDia2-DAD peptides inhibited glioblastoma motility and invasion in vitro and ex vivo rat brain slices. However, SMIFH2, IMMs, and mDia2 DAD efficacy in vivo remains largely unexplored and potential toxicity across a range of developmental phenotypes has not been thoroughly characterized. In this study, we performed an in vivo screen of early life-stage toxicity in Danio rerio zebrafish embryos 2 days post-fertilization (dpf) in response to SMIFH2, IMM01/02, and mDia2 DAD. SMIFH2 at concentrations ≥5–10 μM induced significant defects in developing zebrafish, including shorter body lengths, tail curvature and defective tail cellularity, craniofacial malformations, pericardial edema, absent and/or compromised vasculature function and flow, depressed heart rates and increased mortality. Conversely, IMM and mDia2 DAD peptides were minimally toxic at concentrations up to 10–20 and 50 μM, respectively. SMIFH2's therapeutic potential may therefore be limited by its substantial in vivo toxicity at functional concentrations. mDia formin agonism with IMMs and mDia2 DADs may therefore be a more effective and less toxic anti-invasive therapeutic approach. PMID:29692731

Different forms of MARCKS protein are involved in memory formation in the learning process of imprinting.

PubMed

Solomonia, Revaz O; Apkhazava, David; Nozadze, Maia; Jackson, Antony P; McCabe, Brian J; Horn, Gabriel

2008-06-01

There is strong evidence that a restricted part of the chick forebrain, the IMM (formerly IMHV), stores information acquired through the learning process of visual imprinting. Twenty-four hours after imprinting training, a learning-specific increase in amount of myristoylated, alanine-rich C-kinase substrate (MARCKS) protein is known to occur in the homogenate fraction of IMM. We investigated the two components of this fraction, membrane-bound and cytoplasmic-phosphorylated MARCKS. In IMM, amount of membrane-bound MARCKS, but not of cytoplasmic-phosphorylated MARCKS, increased as chicks learned. No changes were observed for either form of MARCKS in PPN, a control forebrain region. The results indicate that there is a learning-specific increase in membrane-bound, non-phosphorylated MARCKS 24 h after training. This increase might contribute to stabilization of synaptic morphology.

ImmPort, toward repurposing of open access immunological assay data for translational and clinical research.

PubMed

Bhattacharya, Sanchita; Dunn, Patrick; Thomas, Cristel G; Smith, Barry; Schaefer, Henry; Chen, Jieming; Hu, Zicheng; Zalocusky, Kelly A; Shankar, Ravi D; Shen-Orr, Shai S; Thomson, Elizabeth; Wiser, Jeffrey; Butte, Atul J

2018-02-27

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components-Private Data, Shared Data, Data Analysis, and Resources-for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the Shared Data portal (www.immport.org/immport-open), which allows research data to be repurposed to accelerate the translation of new insights into discoveries.

Ion mobility-mass spectrometry as a tool to investigate protein-ligand interactions.

PubMed

Göth, Melanie; Pagel, Kevin

2017-07-01

Ion mobility-mass spectrometry (IM-MS) is a powerful tool for the simultaneous analysis of mass, charge, size, and shape of ionic species. It allows the characterization of even low-abundant species in complex samples and is therefore particularly suitable for the analysis of proteins and their assemblies. In the last few years even complex and intractable species have been investigated successfully with IM-MS and the number of publications in this field is steadily growing. This trend article highlights recent advances in which IM-MS was used to study protein-ligand complexes and in particular focuses on the catch and release (CaR) strategy and collision-induced unfolding (CIU). Graphical Abstract Native mass spectrometry and ion mobility-mass spectrometry are versatile tools to follow the stoichiometry, energetics, and structural impact of protein-ligand binding.

Neural basis of imprinting behavior in chicks.

PubMed

Nakamori, Tomoharu; Maekawa, Fumihiko; Sato, Katsushige; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2013-01-01

Newly hatched chicks memorize the characteristics of the first moving object they encounter, and subsequently show a preference for it. This "imprinting" behavior is an example of infant learning and is elicited by visual and/or auditory cues. Visual information of imprinting stimuli in chicks is first processed in the visual Wulst (VW), a telencephalic area corresponding to the mammalian visual cortex, congregates in the core region of the hyperpallium densocellulare (HDCo) cells, and transmitted to the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. The imprinting memory is stored in the IMM, and activities of IMM neurons are altered by imprinting. Imprinting also induces functional and structural plastic changes of neurons in the circuit that links the VW and the IMM. Of these neurons, the activity of the HDCo cells is strongly influenced by imprinting. Expression and modulation of NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptors in the HDCo cells are crucial for plastic changes in this circuit as well as the process of visual imprinting. Thus, elucidation of cellular and molecular mechanisms underlying the plastic changes that occurred in the HDCo cells may provide useful knowledge about infant learning. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Production of Omega-3 Fatty Acid Ethyl Esters from Menhaden Oil Using Proteus vulgaris Lipase-Mediated One-Step Transesterification and Urea Complexation.

PubMed

Kim, Soo-Jin; Kim, Hyung Kwoun

2016-05-01

An organic solvent-stable lipase from Proteus vulgaris K80 was used to produce the omega-3 polyunsaturated fatty acid ethyl esters (ω-3 PUFA EEs). First, the lyophilized recombinant lipase K80 (LyoK80) was used to perform the transesterification reaction of menhaden oil and ethanol. LyoK80 produced the ω-3 PUFA EEs with a conversion yield of 82 % in the presence of 20 % water content via a three-step ethanol-feeding process; however, in a non-aqueous condition, LyoK80 produced only a slight amount of the ω-3 PUFA EEs. To enhance its reaction properties, the lipase K80 was immobilized on a hydrophobic bead to derive ImmK80; the biochemical properties and substrate specificity of ImmK80 are similar to those of LyoK80. ImmK80 was then used to produce ω-3 PUFA EEs in accordance with the same transesterification reaction. Unlike LyoK80, ImmK80 achieved a high ω-3 PUFA EE conversion yield of 86 % under a non-aqueous system via a one-step ethanol-feeding reaction. The ω-3 PUFA EEs were purified up to 92 % using a urea complexation method.

[Analysis of elderly outpatients in relation to nutritional status, sarcopenia, renal function, and bone density].

PubMed

Salmaso, Franciany Viana; Vigário, Patrícia dos Santos; Mendonça, Laura Maria Carvalho de; Madeira, Miguel; Vieira Netto, Leonardo; Guimarães, Marcela Rodrigues Moreira; Farias, Maria Lucia Fleiuss de

2014-04-01

To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women. We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m(2), body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height(2). We used the Pearson correlation coefficient, p < 0.05 as significant. MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG. CONCLUSIONS The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.

Insights on the mechanism of action of immunostimulants in relation to their pharmacological potency. The effects of imidazoquinolines on TLR8.

PubMed

Kubli-Garfias, Carlos; Vázquez-Ramírez, Ricardo; Trejo-Muñoz, Cynthia; Berber, Arturo

2017-01-01

Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1. These structural differences alter immune responses, such as the production of interferon regulatory factor and nuclear factor-κB (IRF-NFκB). In this work, quantum mechanics theory and computational chemistry methods were applied to study the physicochemical properties of the crystal binding site of TLR8 complexed with the following six IMMS molecules: Hybrid-2, XG1-236, DS802, CL075, CL097 and R848 (resiquimod). The PDB IDs of the crystals were: 4R6A, 4QC0, 4QBZ, 3W3K, 3W3J, and 3W3N respectively. Thus, were calculated, the total energy, solvation energy, interaction energy (instead of free energy) of the system and interaction energy of the polar region of the IMMS. Additionally, the dipole moment, electrostatic potential, polar surface, atomic charges, hydrogen bonds, and polar and hydrophobic interactions, among others, were assessed. Together, these properties revealed important differences among the six TLR8-immunostimulant complexes, reflected as different interaction energies and therefore different electrostatic environments and binding energies. Remarkably, the interaction energy of a defined polar region composed of the highly polarized N3, N5 atoms and the N11 amino group, acted as a polar pharmacophore that correlates directly with the reported immunopharmacological potency of the six complexed molecules. Based on these results, it was concluded that accurate physicochemical analysis of the crystal binding site could reveal the binding energy (measured as interaction energy) and associated molecular mechanism of action between IMMS and TLR8. These findings may facilitate the development and design of improved small molecules with IMMS properties that are targeted to the TLR system and have enhanced pharmacological effectiveness and reduced toxicity.

Insights on the mechanism of action of immunostimulants in relation to their pharmacological potency. The effects of imidazoquinolines on TLR8

PubMed Central

Kubli-Garfias, Carlos; Vázquez-Ramírez, Ricardo; Trejo-Muñoz, Cynthia; Berber, Arturo

2017-01-01

Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1. These structural differences alter immune responses, such as the production of interferon regulatory factor and nuclear factor-κB (IRF-NFκB). In this work, quantum mechanics theory and computational chemistry methods were applied to study the physicochemical properties of the crystal binding site of TLR8 complexed with the following six IMMS molecules: Hybrid-2, XG1-236, DS802, CL075, CL097 and R848 (resiquimod). The PDB IDs of the crystals were: 4R6A, 4QC0, 4QBZ, 3W3K, 3W3J, and 3W3N respectively. Thus, were calculated, the total energy, solvation energy, interaction energy (instead of free energy) of the system and interaction energy of the polar region of the IMMS. Additionally, the dipole moment, electrostatic potential, polar surface, atomic charges, hydrogen bonds, and polar and hydrophobic interactions, among others, were assessed. Together, these properties revealed important differences among the six TLR8-immunostimulant complexes, reflected as different interaction energies and therefore different electrostatic environments and binding energies. Remarkably, the interaction energy of a defined polar region composed of the highly polarized N3, N5 atoms and the N11 amino group, acted as a polar pharmacophore that correlates directly with the reported immunopharmacological potency of the six complexed molecules. Based on these results, it was concluded that accurate physicochemical analysis of the crystal binding site could reveal the binding energy (measured as interaction energy) and associated molecular mechanism of action between IMMS and TLR8. These findings may facilitate the development and design of improved small molecules with IMMS properties that are targeted to the TLR system and have enhanced pharmacological effectiveness and reduced toxicity. PMID:28582454

Collision cross sections of high-mannose N-glycans in commonly observed adduct states--identification of gas-phase conformers unique to [M-H](-) ions.

PubMed

Struwe, W B; Benesch, J L; Harvey, D J; Pagel, K

2015-10-21

We report collision cross sections (CCS) of high-mannose N-glycans as [M + Na](+), [M + K](+), [M + H](+), [M + Cl](-), [M + H2PO4](-) and [M - H](-) ions, measured by drift tube (DT) ion mobility-mass spectrometry (IM-MS) in helium and nitrogen gases. Further analysis using traveling wave (TW) IM-MS reveal the existence of distinct conformers exclusive to [M - H](-) ions.

Mass Spectrometry and Ion Mobility Characterization of Bioactive Peptide-Synthetic Polymer Conjugates.

PubMed

Alalwiat, Ahlam; Tang, Wen; Gerişlioğlu, Selim; Becker, Matthew L; Wesdemiotis, Chrys

2017-01-17

The bioconjugate BMP2-(PEO-HA) 2 , composed of a dendron with two monodisperse poly(ethylene oxide) (PEO) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone growth stimulating peptide (BMP2), has been comprehensively characterized by mass spectrometry (MS) methods, encompassing matrix-assisted laser desorption ionization (MALDI), electrospray ionization (ESI), tandem mass spectrometry (MS 2 ), and ion mobility mass spectrometry (IM-MS). MS 2 experiments using different ion activation techniques validated the sequences of the synthetic, bioactive peptides HA and BMP2, which contained highly basic amino acid residues either at the N-terminus (BMP2) or C-terminus (HA). Application of MALDI-MS, ESI-MS, and IM-MS to the polymer-peptide biomaterial confirmed its composition. Collision cross-section measurements and molecular modeling indicated that BMP2-(PEO-HA) 2 exists in several folded and extended conformations, depending on the degree of protonation. Protonation of all basic sites of the hybrid material nearly doubles its conformational space and accessible surface area.

Device characterization for design optimization of 4 junction inverted metamorphic concentrator solar cells

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

Geisz, John F.; France, Ryan M.; Steiner, Myles A.

Quantitative electroluminescence (EL) and luminescent coupling (LC) analysis, along with more conventional characterization techniques, are combined to completely characterize the subcell JV curves within a fourjunction (4J) inverted metamorphic solar cell (IMM). The 4J performance under arbitrary spectral conditions can be predicted from these subcell JV curves. The internal radiative efficiency (IRE) of each junction has been determined as a function of current density from the external radiative efficiency using optical modeling, but this required the accurate determination of the individual junction current densities during the EL measurement as affected by LC. These measurement and analysis techniques can be appliedmore » to any multijunction solar cell. The 4J IMM solar cell used to illustrate these techniques showed excellent junction quality as exhibited by high IRE and a one-sun AM1.5D efficiency of 36.3%. This device operates up to 1000 suns without limitations due to any of the three tunnel junctions.« less

Clinical Outcome Metrics for Optimization of Robust Training

NASA Technical Reports Server (NTRS)

Ebert, D.; Byrne, V. E.; McGuire, K. M.; Hurst, V. W., IV; Kerstman, E. L.; Cole, R. W.; Sargsyan, A. E.; Garcia, K. M.; Reyes, D.; Young, M.

2016-01-01

Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance (pre-IMM analysis) and overall mitigation of the mission medical impact (IMM analysis); 2) refine the procedure outcome and clinical outcome metrics themselves; 3) refine or develop innovative medical training products and solutions to maximize CMO performance; and 4) validate the methods and products of this experiment for operational use in the planning, execution, and quality assurance of the CMO training process The team has finalized training protocols and developed a software training/testing tool in collaboration with Butler Graphics (Detroit, MI). In addition to the "hands on" medical procedure modules, the software includes a differential diagnosis exercise (limited clinical decision support tool) to evaluate the diagnostic skills of participants. Human subject testing will occur over the next year.

Alternative forms of lethality in mitomycin C-induced bacteria carrying ColE1 plasmids

PubMed Central

Suit, Joan L.; Fan, M.-L. Judy; Sabik, Joseph F.; Labarre, Robert; Luria, S. E.

1983-01-01

We have studied the physiological effects of mitomycin C induction on cells carrying ColE1 plasmids with differing configurations of three genes: the structural gene coding for colicin (cea), a gene responsible for mitomycin C lethality (kil) that we located as part of an operon with cea, and the immunity (imm) gene, which lies near cea but is not in the same operon. kil is close to or overlaps imm. When cea+ plasmids are present mitomycin C induction results in 100-fold or greater increases in the level of colicin. Within an hour after induction more than 90% of cells carrying cea+kil+ plasmids are killed and macromolecular synthesis stops, capacity for transport of proline, thiomethyl β-D-galactoside, and α-methyl glucoside is lost, and the membrane becomes abnormally permeable as indicated by an increased accessibility of intracellular β-galactosidase to the substrate o-nitrophenyl β-D-galactoside. All of these events occur when a cea-kil+imm+ plasmid is present and none does when the plasmid is cea+kil-imm+, so the damage can be attributed solely to the Kil function and not to the presence of colicin. However, cells carrying a cea+kil-imm- plasmid are killed upon induction, apparently by action of endogenous colicin on the nonimmune cytoplasmic membrane. The pattern of accompanying physiological damage is distinguished from the kil+-associated damage by an enhancement of α-methyl glucoside uptake and accumulation and efflux of α-methyl glucoside 6-phosphate and by an absence of the alteration in membrane permeability for o-nitrophenyl β-D-galactoside. These features are typical of colicin E1 action on the membrane. The induced damage is not prevented by trypsin and occurs in cells of a strain specifically tolerant to exogenous colicin E1, indicating that the attack is from inside the cell. PMID:6403939

Optimization of HAART with genetic algorithms and agent-based models of HIV infection.

PubMed

Castiglione, F; Pappalardo, F; Bernaschi, M; Motta, S

2007-12-15

Highly Active AntiRetroviral Therapies (HAART) can prolong life significantly to people infected by HIV since, although unable to eradicate the virus, they are quite effective in maintaining control of the infection. However, since HAART have several undesirable side effects, it is considered useful to suspend the therapy according to a suitable schedule of Structured Therapeutic Interruptions (STI). In the present article we describe an application of genetic algorithms (GA) aimed at finding the optimal schedule for a HAART simulated with an agent-based model (ABM) of the immune system that reproduces the most significant features of the response of an organism to the HIV-1 infection. The genetic algorithm helps in finding an optimal therapeutic schedule that maximizes immune restoration, minimizes the viral count and, through appropriate interruptions of the therapy, minimizes the dose of drug administered to the simulated patient. To validate the efficacy of the therapy that the genetic algorithm indicates as optimal, we ran simulations of opportunistic diseases and found that the selected therapy shows the best survival curve among the different simulated control groups. A version of the C-ImmSim simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html

Time correlation between mononucleosis and initial symptoms of MS

PubMed Central

Endriz, John; Ho, Peggy P.

2017-01-01

Objective: To determine the average age of MS onset vs the age at which Epstein-Barr infection has previously occurred and stratify this analysis by sex and the blood level of Epstein-Barr nuclear antigen 1 (EBNA1) antibody. Methods: Using infectious mononucleosis (IM) as a temporal marker in data from the Swedish epidemiologic investigation of MS, 259 adult IM/MS cases were identified and then augmented to account for “missing” childhood data so that the average age of MS onset could be determined for cases binned by age of IM (as stratified by sex and EBNA1 titer level). Results: Mean age of IM vs mean age of MS reveals a positive time correlation for all IM ages (from ∼5 to ∼30 years), with IM-to-MS delay decreasing with increased age. When bifurcated by sex or EBNA1 blood titer levels, males and high-titer subpopulations show even stronger positive time correlation, while females and low-titer populations show negative time correlation in early childhood (long IM/MS delay). The correlation becomes positive in females beyond puberty. Conclusions: IM/MS time correlation implies causality if IM is time random. Alternative confounding models seem implausible, in light of constraints imposed by time-invariant delay observed here. Childhood infection with Epstein-Barr virus (EBV) in females and/or those genetically prone to low EBNA1 blood titers will develop MS slowly. Males and/or high EBNA1-prone develop MS more rapidly following IM infection at all ages. For all, postpubescent EBV infection is critical for the initiation and rapid development of MS. PMID:28271078

Preliminary evidence of a neurophysiological basis for individual discrimination in filial imprinting.

PubMed

Town, Stephen Michael

2011-12-01

Filial imprinting involves a predisposition for biologically important stimuli and a learning process directing preferences towards a particular stimulus. Learning underlies discrimination between imprinted and unfamiliar individuals and depends upon the IMM (intermediate and medial mesopallium). Here, IMM neurons responded differentially to familiar and unfamiliar conspecifics following socialization and the neurophysiological effects of social experience differed between hemispheres. Such findings may provide a neurophysiological basis for individual discrimination in imprinting. Copyright © 2011 Elsevier B.V. All rights reserved.

A mission design for International Manned Mars Mission - From the 1991 International Space University (ISU) Design Project

NASA Technical Reports Server (NTRS)

Mendell, Wendell W.

1991-01-01

The International Space University (ISU) conducted a study of an international program to support human exploration of Mars as its annual Design Project activity during its 1991 summer session in Toulouse, France. Although an ISU Design Project strives to produce an in-depth analysis during the intense 10-week summer session, the International Mars Mission (IMM) project was conducted in a manner designed to provide a learning experience for young professionals working in an unusual multidisciplinary and multinational environment. The breadth of the IMM study exceeds that of most Mars mission studies of the past, encompassing political organization for long-term commitment, multinational management structure, cost analysis, mission architecture, vehicle configuration, crew health, life support, Mars surface infrastructure, mission operations, technology evaluation, risk assessment, scientific planning, exploration, communication networks, and Martian resource utilization. The IMM Final Report has particular value for those seeking insight into the choices made by a multinational group working in an apolitical environment on the problems of international cooperation in space.

A defect in the thymidine kinase 2 gene causing isolated mitochondrial myopathy without mtDNA depletion.

PubMed

Leshinsky-Silver, E; Michelson, M; Cohen, S; Ginsberg, M; Sadeh, M; Barash, V; Lerman-Sagie, T; Lev, D

2008-07-01

Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.

Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division

PubMed Central

Cho, Bongki; Cho, Hyo Min; Jo, Youhwa; Kim, Hee Dae; Song, Myungjae; Moon, Cheil; Kim, Hyongbum; Kim, Kyungjin; Sesaki, Hiromi; Rhyu, Im Joo; Kim, Hyun; Sun, Woong

2017-01-01

Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons. Although CoMIC is potentiated by inhibition of Drp1 and occurs at the potential division spots contacting the endoplasmic reticulum, it appears on IMM independently of OMM. Intra-mitochondrial influx of Ca2+ induces and potentiates CoMIC, and leads to K+-mediated mitochondrial bulging and depolarization. Synergistically, optic atrophy 1 (Opa1) also regulates CoMIC via controlling Mic60-mediated OMM–IMM tethering. Therefore, we propose that CoMIC is a priming event for efficient mitochondrial division. PMID:28598422

Ultra-High Resolution Ion Mobility Separations Utilizing Traveling Waves in a 13 m Serpentine Path Length Structures for Lossless Ion Manipulations Module

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

Deng, Liulin; Ibrahim, Yehia M.; Hamid, Ahmed M.

We report the development and initial evaluation of a 13-m path length Structures for Lossless Manipulations (SLIM) module for achieving high resolution separations using traveling waves (TW) with ion mobility (IM) spectrometry. The TW SLIM module was fabricated using two mirror-image printed circuit boards with appropriately configured RF, DC and TW electrodes and positioned with a 2.75-mm inter-surface gap. Ions were effective confined between the surfaces by RF-generated pseudopotential fields and moved losslessly through a serpentine path including 44 “U” turns using TWs. The ion mobility resolution was characterized at different pressures, gaps between the SLIM surfaces, TW and RFmore » parameters. After initial optimization the SLIM IM-MS module provided about 5-fold higher resolution separations than present commercially available drift tube or traveling wave IM-MS platforms. Peak capacity and peak generation rates achieved were 246 and 370 s-1, respectively, at a TW speed of 148 m/s. The high resolution achieved in the TW SLIM IM-MS enabled e.g., isomeric sugars (Lacto-N-fucopentaose I and Lacto-N-fucopentaose II) to be baseline resolved, and peptides from a albumin tryptic digest much better resolved than with existing commercial IM-MS platforms. The present work also provides a foundation for the development of much higher resolution SLIM devices based upon both considerably longer path lengths and multi-pass designs.« less

Effectiveness of Interactive Multimedia Environment on Language Acquisition Skills of 6th Grade Students in the United Arab Emirates

ERIC Educational Resources Information Center

Almekhlafi, Abdurrahman Ghaleb

2006-01-01

This study investigated the effect of interactive multimedia (IMM) program on students' acquisition of some English as a second language (ESL) skills. An interactive multimedia CD-ROM was used with ninety 6th grade ESL students in Al-Ain Model School 2, United Arab Emirates. Students were selected and divided into experimental and control groups…

Collection and processing of lymph nodes from large animals for RNA analysis: preparing for lymph node transcriptomic studies of large animal species

USDA-ARS?s Scientific Manuscript database

Large animals (both livestock and wildlife) serve as important reservoirs of zoonotic pathogens, including Brucella, Salmonella, and E. coli, as well as useful models for the study of pathogenesis and/or spread of the bacteria in non-murine hosts. With the key function of lymph nodes in the host imm...

Performance Evaluation Within CASE_ATTI of MHT and JVC Association Algorithms for COMDAT TD

DTIC Science & Technology

2007-05-01

les résultats du travail effectué dans le cadre de l’analyse de sensibilité des algorithmes uti- lisés dans COMDAT, comparativement à ceux...is also very important in tracking system. Neverthe- less, tracking performance with even the best designed filter may become very degraded in the...for completeness. 2.2 IMM Some practical model of target motion is assumed for the design of the Kalman filter. This target kinematics model is

The Effect of Pressure and Time on Information Recall

DTIC Science & Technology

2008-04-01

retenu que 69 % de l’information visualisée à une profondeur de 40 m, comparativement à 90 % de celle-ci dans le cas d’un signalement immédiat. Après 2...from the diver, so it is vital that the diver proves complete and accurate information. This study was designed to quantify the amount and type of...de l’information sur l’objectif, comparativement à 90 % de celle-ci dans le cas d’un signalement immédiat. Après 2 heures, les plongeurs n’ont

Optimizing Medical Kits for Spaceflight

NASA Technical Reports Server (NTRS)

Keenan, A. B,; Foy, Millennia; Myers, G.

2014-01-01

The Integrated Medical Model (IMM) is a probabilistic model that estimates medical event occurrences and mission outcomes for different mission profiles. IMM simulation outcomes describing the impact of medical events on the mission may be used to optimize the allocation of resources in medical kits. Efficient allocation of medical resources, subject to certain mass and volume constraints, is crucial to ensuring the best outcomes of in-flight medical events. We implement a new approach to this medical kit optimization problem. METHODS We frame medical kit optimization as a modified knapsack problem and implement an algorithm utilizing a dynamic programming technique. Using this algorithm, optimized medical kits were generated for 3 different mission scenarios with the goal of minimizing the probability of evacuation and maximizing the Crew Health Index (CHI) for each mission subject to mass and volume constraints. Simulation outcomes using these kits were also compared to outcomes using kits optimized..RESULTS The optimized medical kits generated by the algorithm described here resulted in predicted mission outcomes more closely approached the unlimited-resource scenario for Crew Health Index (CHI) than the implementation in under all optimization priorities. Furthermore, the approach described here improves upon in reducing evacuation when the optimization priority is minimizing the probability of evacuation. CONCLUSIONS This algorithm provides an efficient, effective means to objectively allocate medical resources for spaceflight missions using the Integrated Medical Model.

Infliximab in ulcerative colitis: real-life analysis of factors predicting treatment discontinuation due to lack of response or colectomy: ECIA (ACAD Colitis and Infliximab Study).

PubMed

Fernández-Salazar, Luis; Muñoz, Fernando; Barrio, Jesús; Muñoz, Concepción; Pajares, Ramón; Rivero, Montserrat; Prieto, Vanessa; Legido, Jesús; Bouhmidi, Abdel; Herranz, Maite; Fernández, Nereida; Sánchez-Ocaña, Ramón; Joao, Diana; Santos, Fernando

2016-01-01

To describe clinical practice with infliximab (IFX) in ulcerative colitis (UC); identification of predictive factors for IFX treatment discontinuation due to insufficient response and for colectomy. Retrospective, multicentric and observational study including every UC IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological data; variables for poor prognosis; IFX prior treatments; characteristics of the IFX treatment; time from the UC diagnosis to induction with IFX; time from induction to colectomy or until data collection. Predictive and protective factors for IFX discontinuation due to lack of response and for colectomy were analyzed with binary logistic regression and Cox analysis. Follow-up time from induction with IFX to the collection of data or colectomy: 36.7 ± 25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX + immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%. Independent predictive or protective factors for IFX discontinuation: IMM resistance (OR: 2.9, p = 0.022, 95% CI: 1.2-7.2), prior use of leukocytapheresis (OR: 3.3, p = 0.024, 95% CI: 1.1-9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.9, and HR: 0.4, p = 0.006, 95% CI: 0.2-0.8) and corticosteroid use in induction (HR: 1.9, p = 0.049, 95% CI: 1.0-3.8). Independent predictive or protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036, 95% CI: 1.1-8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.8, and HR: 0.3, p = 0.011, 95% CI: 0.1-0.8) and severe cortico-resistant flare-up (HR: 2.5, p = 0.032, 95% CI: 1.1-5.9). Prior use of IMM and leukocytapheresis, the use of corticosteroids in induction and a severe cortico-resistant flare predict a worse response to IFX and the need for colectomy. Combination therapy is a protective factor for both.

Thirty years of collaboration with Gabriel Horn.

PubMed

Bateson, Patrick

2015-03-01

All the collaborative work described in this review was on the process of behavioural imprinting occurring early in the life of domestic chicks. Finding a link between learning and a change in the brain was only a first step in establishing a representation of the imprinting object. A series of overlapping experiments were necessary to eliminate alternative explanations. Once completed, a structure, the intermediate and medial mesopallium (IMM), was found to be strongly linked to the formation of a neural representation of the object used for imprinting the birds. With the site identified, lesion experiments showed that it was necessary for imprinting but not associative learning. Also the two sides of the brain responded differently with the left IMM acting as a permanent store and the right side acting as a way station to other parts of the brain. The collaborative work led to many studies by Gabriel Horn with others on the molecular and cellular bases of imprinting, and also to neural net modelling and behavioural studies with me on the nature of category formation in intact animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition.

PubMed

Balakirev, M Y; Zimmer, G

1998-08-01

Some compounds are known to induce solute-nonselective permeability of the inner mitochondrial membrane (IMM) in Ca2+-loaded mitochondria. Existing data suggest that this process, following the opening of a mitochondrial permeability transition pore, is preceded by different solute-selective permeable states of IMM. At pH 7, for instance, the K0.5 for Ca2+-induced pore opening is 16 microM, a value 80-fold above a therapeutically relevant shift of intracellular Ca2+ during ischemia in vivo. The present work shows that in the absence of Ca2+, phenylarsine oxide and tetraalkyl thiuram disulfides (TDs) are able to induce a complex sequence of IMM permeability changes. At first, these agents activated an electrogenic K+ influx into the mitochondria. This K+-specific pathway had K0.5 = 35 mM for K+ and was inhibited by bromsulfalein with Ki = 2.5 microM. The inhibitors of mitochondrial KATP channel, ATP and glibenclamide, did not inhibit K+ transport via this pathway. Moreover, 50 microM glibenclamide induced by itself K+ influx into the mitochondria. After the increase in K+ permeability of IMM, mitochondria become increasingly permeable to protons. Mechanisms of H+ leak and nonselective permeability increase could also be different depending on the type of mitochondrial permeability transition (MPT) inducer. Thus, permeabilization of mitochondria induced by phenylarsine oxide was fully prevented by ADP and/or cyclosporin A, whereas TD-induced membrane alterations were insensitive toward these inhibitors. It is suggested that MPT in vivo leading to irreversible apoptosis is irrelevant in reversible ischemia/reperfusion injury. Copyright 1998 Academic Press.

Molecular mechanisms of memory in imprinting.

PubMed

Solomonia, Revaz O; McCabe, Brian J

2015-03-01

Converging evidence implicates the intermediate and medial mesopallium (IMM) of the domestic chick forebrain in memory for a visual imprinting stimulus. During and after imprinting training, neuronal responsiveness in the IMM to the familiar stimulus exhibits a distinct temporal profile, suggesting several memory phases. We discuss the temporal progression of learning-related biochemical changes in the IMM, relative to the start of this electrophysiological profile. c-fos gene expression increases <15 min after training onset, followed by a learning-related increase in Fos expression, in neurons immunopositive for GABA, taurine and parvalbumin (not calbindin). Approximately simultaneously or shortly after, there are increases in phosphorylation level of glutamate (AMPA) receptor subunits and in releasable neurotransmitter pools of GABA and taurine. Later, the mean area of spine synapse post-synaptic densities, N-methyl-D-aspartate receptor number and phosphorylation level of further synaptic proteins are elevated. After ∼ 15 h, learning-related changes in amounts of several synaptic proteins are observed. The results indicate progression from transient/labile to trophic synaptic modification, culminating in stable recognition memory. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

[Effect of filial imprinting procedure on cell proliferation in the chick brain].

PubMed

Komissarova, N V; Anokhin, K V

2007-01-01

In the present study we tested the hypothesis that memory formation during visual imprinting might be related to generation of new cells in the brain of newborn domestic chicks. Cell proliferation was examined in the intermediate medial mesopallium (IMM), arcopallium intermedium (AI), medial part of nidopallium and mesopallium (MNM), nidopallium dorso-caudalis (Ndc), hippocampus (Hp) and area parahippocampalis (APH), as well as in corresponding ventricular zones. Number of new cells was measured by BrdU incorporation 24 h or 7 days after training, BrdU was injected before training. 24 h after imprinting the number of BrdU-positive cells increased significantly in IMM. 7 days after training no changes were observed in IMM, while the number of new cells decreased in MNM and Ndc in comparison to the control group. These data suggest that newly generated cells in the brain of young chicks are influenced by imprinting procedure, which has opposite short-term and long-term effects. A possible reason for such double action of imprinting in contrast to conventional learning can be its additional stimulation of development of predisposition for features of natural parents.

Molecular mechanisms of memory in imprinting

PubMed Central

Solomonia, Revaz O.; McCabe, Brian J.

2015-01-01

Converging evidence implicates the intermediate and medial mesopallium (IMM) of the domestic chick forebrain in memory for a visual imprinting stimulus. During and after imprinting training, neuronal responsiveness in the IMM to the familiar stimulus exhibits a distinct temporal profile, suggesting several memory phases. We discuss the temporal progression of learning-related biochemical changes in the IMM, relative to the start of this electrophysiological profile. c-fos gene expression increases <15 min after training onset, followed by a learning-related increase in Fos expression, in neurons immunopositive for GABA, taurine and parvalbumin (not calbindin). Approximately simultaneously or shortly after, there are increases in phosphorylation level of glutamate (AMPA) receptor subunits and in releasable neurotransmitter pools of GABA and taurine. Later, the mean area of spine synapse post-synaptic densities, N-methyl-d-aspartate receptor number and phosphorylation level of further synaptic proteins are elevated. After ∼15 h, learning-related changes in amounts of several synaptic proteins are observed. The results indicate progression from transient/labile to trophic synaptic modification, culminating in stable recognition memory. PMID:25280906

Generalized isobaric multiplet mass equation and its application to the Nolen-Schiffer anomaly

NASA Astrophysics Data System (ADS)

Dong, J. M.; Zhang, Y. H.; Zuo, W.; Gu, J. Z.; Wang, L. J.; Sun, Y.

2018-02-01

The Wigner isobaric multiplet mass equation (IMME) is the most fundamental prediction in nuclear physics with the concept of isospin. However, it was deduced based on the Wigner-Eckart theorem with the assumption that all charge-violating interactions can be written as tensors of rank two. In the present work, the charge-symmetry breaking (CSB) and charge-independent breaking (CIB) components of the nucleon-nucleon force, which contribute to the effective interaction in nuclear medium, are established in the framework of Brueckner theory with AV18 and AV14 bare interactions. Because such charge-violating components can no longer be expressed as an irreducible tensor due to density dependence, its matrix element cannot be analytically reduced by the Wigner-Eckart theorem. With an alternative approach, we derive a generalized IMME (GIMME) that modifies the coefficients of the original IMME. As the first application of GIMME, we study the long-standing question of the origin of the Nolen-Schiffer anomaly (NSA) found in the Coulomb displacement energy of mirror nuclei. We find that the naturally emerged CSB term in GIMME is largely responsible for explaining the NSA.

Development of a High Volume Capable Process to Manufacture High Performance Photovoltaic Cells: Cooperative Research and Development Final Report, CRADA Number CRD-08-322

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

Geisz, J. F.

2012-11-01

The intent of the work is for RFMD and NREL to cooperate in the development of a commercially viable and high volume capable process to manufacture high performance photovoltaic cells, based on inverted metamorphic (IMM) GaAs technology. The successful execution of the agreement will result in the production of a PV cell using technology that is capable of conversion efficiency at par with the market at the time of release (reference 2009: 37-38%), using RFMD's production facilities. The CRADA work has been divided into three phases: (1) a foundation phase where the teams will demonstrate the manufacturing of a basicmore » PV cell at RFMD's production facilities; (2) a technology demonstration phase where the teams will demonstrate the manufacturing of prototype PV cells using IMM technology at RFMD's production facilities, and; (3) a production readiness phase where the teams will demonstrate the capability to manufacture PV cells using IMM technology with high yields, high reliability, high reproducibility and low cost.« less

Revalidation of the Isobaric Multiplet Mass Equation for the A =20 quintet

NASA Astrophysics Data System (ADS)

Glassman, Brent; Perez-Loureiro, D.; Wrede, C.; Allen, J.; Bardyan, D.; Bennett, M.; Brown, A.; Chipps, K.; Febbraro, M.; Fry, Cathleen; Hall, O.; Hall, M.; Liddick, S.; O'Malley, P.; Ong, W.; Pain, S.; Schwartz, S.; Shidling, P.; Sims, H.; Thompson, P.; Zhang, E.

2016-03-01

An unexpected breakdown of the Isobaric Multiplet Mass Equation (IMME) for the A =20, T =2 quintet was recently reported based on a precise measurement of the 20Mg mass and adopted data on the other members. The adopted value for 20Na presented the greatest deviation from the IMME fit and was based on relatively imprecise beta delayed proton decay measurements. We used the superallowed 0+ to 0+ beta decay of 20Mg to feed the lowest T =2 state in 20Na, and the high purity germanium detector array SeGA to detect its gamma-ray de-excitation for the first time. Using the gamma-ray energies, we were able to precisely measure the excitation energy to be 6498.4 +/-0 .2stat+/-0.4syst keV. By incorporating this newly measured value we find that the IMME is revalidated. We gratefully acknowledge the NSCL staff for technical assistance and for providing the 20Mg beam. This work was supported by the National Science Foundation (USA) under Grants No. PHY-1102511, No. PHY-1419765, and No. PHY-1404442.

Building a Six-Junction Inverted Metamorphic Concentrator Solar Cell

DOE PAGES

Geisz, John F.; Steiner, Myles A.; Jain, Nikhil; ...

2017-12-20

We propose practical six-junction (6J) inverted metamorphic multijunction (IMM) concentrator solar cell designs with the potential to exceed 50% efficiency using moderately high quality junction materials. We demonstrate the top three junctions and their monolithic integration lattice matched to GaAs using 2.1-eV AlGaInP, 1.7-eV AlGaAs or GaInAsP, and 1.4-eV GaAs with external radiative efficiencies >0.1%. We demonstrate tunnel junctions with peak tunneling current >400 A/cm 2 that are transparent to <2.1-eV light. We compare the bottom three GaInAs(p) junctions with bandgaps of 1.2, 1.0, and 0.7 eV grown on InP and transparent metamorphic grades with low dislocation densities. The solutionmore » to an integration challenge resulting from Zn diffusion in the GaAs junction is illustrated in a five-junction IMM. Excellent 1-sun performance is demonstrated in a complete 6J IMM device with VOC = 5.15 V, and a promising pathway toward >50% efficiency at high concentrations is presented.« less

Building a Six-Junction Inverted Metamorphic Concentrator Solar Cell

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

Geisz, John F.; Steiner, Myles A.; Jain, Nikhil

We propose practical six-junction (6J) inverted metamorphic multijunction (IMM) concentrator solar cell designs with the potential to exceed 50% efficiency using moderately high quality junction materials. We demonstrate the top three junctions and their monolithic integration lattice matched to GaAs using 2.1-eV AlGaInP, 1.7-eV AlGaAs or GaInAsP, and 1.4-eV GaAs with external radiative efficiencies >0.1%. We demonstrate tunnel junctions with peak tunneling current >400 A/cm 2 that are transparent to <2.1-eV light. We compare the bottom three GaInAs(p) junctions with bandgaps of 1.2, 1.0, and 0.7 eV grown on InP and transparent metamorphic grades with low dislocation densities. The solutionmore » to an integration challenge resulting from Zn diffusion in the GaAs junction is illustrated in a five-junction IMM. Excellent 1-sun performance is demonstrated in a complete 6J IMM device with VOC = 5.15 V, and a promising pathway toward >50% efficiency at high concentrations is presented.« less

Digestibility and retention of zinc, copper, manganese, iron, calcium, and phosphorus in pigs fed diets containing inorganic or organic minerals.

PubMed

Liu, Y; Ma, Y L; Zhao, J M; Vazquez-Añón, M; Stein, H H

2014-08-01

The objective of this experiment was to measure the apparent total tract digestibility (ATTD) and the retention rate of Zn, Cu, Mn, and Fe in pigs fed either inorganic or organic sources of Zn, Cu, Mn, and Fe. The experimental design was a randomized complete block design with a 2 × 3 factorial arrangement of treatments. There were 2 types of diets (corn grits-based or corn-soybean meal [SBM]-based diets) and 3 micromineral treatments (basal micromineral premix [BMM], inorganic micromineral premix [IMM], and organic micromineral premix [OMM]). The BMM contained no added Zn, Cu, Mn, or Fe; the IMM microminerals were provided as sulfates of Zn, Cu, Mn, and Fe at 40, 50, 20, and 100 mg/kg, respectively. The OMM contained the same levels of the 4 microminerals as IMM, but Zn, Cu, Mn, and Fe in this premix were provided by Zn(2-hydroxy-4-methylthio butanoic acid [HMTBa])2, Cu(HMTBa)2, Mn(HMTBa)2, and FeGly, respectively. Forty-eight barrows (initial BW: 31.1 ± 4.2 kg) were housed individually and allowed ad libitum access to the corn grits diet with BMM for 2 wk. All pigs were then moved to metabolism cages and randomly assigned to 1 of the 6 treatment diets with 8 replicates per diet. Fecal and urine samples were collected for 5 d following a 5-d adaptation period. Compared with corn grits diets, pigs fed corn-SBM diets had greater (P < 0.05) absorption and retention of Zn, Cu, and Mn but less (P < 0.05) ATTD of Zn and Cu. Compared with BMM, supplementation of IMM or OMM increased (P < 0.05) absorption, retention, ATTD, and retention rate of Zn, Cu, Mn, and Fe. Compared with IMM, adding OMM to the corn-SBM diet improved (P < 0.05) the absorption and retention of Cu and Mn and the ATTD of Cu, but these differences were not observed in the corn grits diets (interaction, P < 0.05). In addition, adding OMM to the corn-SBM diet increased (P < 0.05) absorption and retention of Zn and Fe and ATTD of Zn, Mn, and Fe compared with adding IMM to the corn-SBM diet. Supplementation of OMM also increased (P < 0.05) the ATTD and retention rate of P in corn-SBM diets. Results indicate that Zn(HMTBa)2 has greater digestibility and Cu(HMTBa)2 and Mn(HMTBa)2 have greater digestibility and retention rates compared with their inorganic sulfates, if included in a corn-SBM diet. Supplementation of organic microminerals also improves the digestibility of P in a corn-SBM diet.

Weathering Tests on Protective Helmets Approved to Australian Standard AS 1698 (for Vehicle Users).

DTIC Science & Technology

1979-11-01

Expanded Polystyrene HELMETI Colour Production; SAA Size ,Length Width j Mass Circumference Date Serial No. cm imm mm nu qm nun L A White July 󈨒 B535336...HELMET DETAILS Make: ARAI Model: S-75 Shell: Fibreglass Reinforced Polyester Resin Liner: Expanded Polystyrene HELMET Colour Production SAA Size...Reinforced Polyester Resin Liner; Expanded Polystyrene (with thin plastic inner shell) HELMET Colour Production’ SAA Size Length Width Mass

First in vivo assessment of "Outwalk": a novel protocol for clinical gait analysis based on inertial and magnetic sensors.

PubMed

Ferrari, Alberto; Cutti, Andrea Giovanni; Garofalo, Pietro; Raggi, Michele; Heijboer, Monique; Cappello, Angelo; Davalli, Angelo

2010-01-01

A protocol named "Outwalk" was recently proposed to measure the thorax-pelvis and lower-limb kinematics during gait in free-living conditions, by means of an inertial and magnetic measurement system (IMMS). The aim of this study was to validate Outwalk on four healthy subjects when it is used in combination with a specific IMMS (Xsens Technologies, NL), against a reference protocol (CAST) and measurement system (optoelectronic system; Vicon, Oxford Metrics Group, UK). For this purpose, we developed an original approach based on three tests, which allowed to separately investigate: (1) the consequences on joint kinematics of the differences between protocols (Outwalk vs. CAST), (2) the accuracy of the hardware (Xsens vs. Vicon), and (3) the summation of protocols' differences and hardware accuracy (Outwalk + Xsens vs. CAST + Vicon). In order to assess joint-angles similarity, the coefficient of multiple correlation (CMC) was used. For test 3, the CMC showed that Outwalk + Xsens and CAST + Vicon kinematics can be interchanged, offset included, for hip, knee and ankle flexion-extension, and hip ab-adduction (CMC > 0.88). The other joint-angles can be interchanged offset excluded (CMC > 0.85). Tests 1 and 2 also showed that differences in offset between joint-angles were predominantly induced by differences in the protocols; differences in correlation by both hardware and protocols; differences in range of motion by the Xsens accuracy. Results thus support the commencement of a clinical trial of Outwalk on transtibial amputees.

Sleep Disruption Medical Intervention Forecasting (SDMIF) Module for the Integrated Medical Model

NASA Technical Reports Server (NTRS)

Lewandowski, Beth; Brooker, John; Mallis, Melissa; Hursh, Steve; Caldwell, Lynn; Myers, Jerry

2011-01-01

The NASA Integrated Medical Model (IMM) assesses the risk, including likelihood and impact of occurrence, of all credible in-flight medical conditions. Fatigue due to sleep disruption is a condition that could lead to operational errors, potentially resulting in loss of mission or crew. Pharmacological consumables are mitigation strategies used to manage the risks associated with sleep deficits. The likelihood of medical intervention due to sleep disruption was estimated with a well validated sleep model and a Monte Carlo computer simulation in an effort to optimize the quantity of consumables. METHODS: The key components of the model are the mission parameter program, the calculation of sleep intensity and the diagnosis and decision module. The mission parameter program was used to create simulated daily sleep/wake schedules for an ISS increment. The hypothetical schedules included critical events such as dockings and extravehicular activities and included actual sleep time and sleep quality. The schedules were used as inputs to the Sleep, Activity, Fatigue and Task Effectiveness (SAFTE) Model (IBR Inc., Baltimore MD), which calculated sleep intensity. Sleep data from an ISS study was used to relate calculated sleep intensity to the probability of sleep medication use, using a generalized linear model for binomial regression. A human yes/no decision process using a binomial random number was also factored into sleep medication use probability. RESULTS: These probability calculations were repeated 5000 times resulting in an estimate of the most likely amount of sleep aids used during an ISS mission and a 95% confidence interval. CONCLUSIONS: These results were transferred to the parent IMM for further weighting and integration with other medical conditions, to help inform operational decisions. This model is a potential planning tool for ensuring adequate sleep during sleep disrupted periods of a mission.

AMPA receptor phosphorylation and recognition memory: learning-related, time-dependent changes in the chick brain following filial imprinting.

PubMed

Solomonia, Revaz O; Meparishvili, Maia; Mikautadze, Ekaterine; Kunelauri, Nana; Apkhazava, David; McCabe, Brian J

2013-04-01

There is strong evidence that a restricted part of the chick forebrain, the intermediate medial mesopallium (IMM), stores information acquired through the learning process of visual imprinting. We have previously demonstrated that at 1 h but not 24 h after imprinting training, a learning-specific increase in the amount of membrane Thr286-autophosphorylated α-calcium/calmodulin-dependent protein kinase II (αCaMKII), and in the proportion of total αCaMKII that is phosphorylated, occurs in the IMM but not in a control brain region, the posterior pole of the nidopallium (PPN). αCaMKII directly phosphorylates Ser831 in the GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. In the present study we have inquired whether the learning-related increase in αCaMKII autophosphorylation is followed by changes in the Ser831 phosphorylation of GluA1 (P-GluA1) and in the total amount of this subunit (T-GluA1). Trained chicks together with untrained control chicks were killed either 1 or 24 h after training. Tissue was removed from the IMM together with tissue from the PPN as a control. Amounts of P-GluA1 and T-GluA1 were measured. In the left IMM of the 1 h group the P-GluA1/T-GluA1 ratio increased in a learning-specific way. No learning-related changes were observed in other brain regions at 1 h or in any region 24 h after training. The results indicate that a time- and regionally-dependent, learning-specific increase in GluA1 phosphorylation occurs early in recognition memory formation.

Mass spectrometry methods for the analysis of biodegradable hybrid materials

NASA Astrophysics Data System (ADS)

Alalwiat, Ahlam

This dissertation focuses on the characterization of hybrid materials and surfactant blends by using mass spectrometry (MS), tandem mass spectrometry (MS/MS), liquid chromatography (LC), and ion mobility (IM) spectrometry combined with measurement and simulation of molecular collision cross sections. Chapter II describes the principles and the history of mass spectrometry (MS) and liquid chromatography (LC). Chapter III introduces the materials and instrumentation used to complete this dissertation. In chapter IV, two hybrid materials containing poly(t-butyl acrylate) (PtBA) or poly(acrylic acid) (PAA) blocks attached to a hydrophobic peptide rich in valine and glycine (VG2), as well as the poly(acrylic acid) (PAA) and VG2 peptide precursor materials, are characterized by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), electrospray ionization mass spectrometry (ESI-MS) and ion mobility mass spectrometry (IM-MS). Collision cross-sections and molecular modeling have been used to determine the final architecture of both hybrid materials. Chapter V investigates a different hybrid material, [BMP-2(HA)2 ], comprised of a dendron with two polyethylene glycol (PEG) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone morphogenic protein mimicking peptide (BMP-2). MALDI-MS, ESI-MS and IM-MS have been used to characterize the HA and BMP-2 peptides. Collisionally activated dissociation (CAD) and electron transfer dissociation (ETD) have been employed in double stage (i.e. tandem) mass spectrometry (MS/MS) experiments to confirm the sequences of the two peptides HA and BMP-2. The MALDI-MS, ESI-MS and IM-MS methods were also applied to characterize the [BMP-2(HA)2] hybrid material. Collision cross-section measurements and molecular modeling indicated that [BMP-2(HA)2] can attain folded or extended conformation, depending on its degree of protonation (charge state). Chapter VI focuses on the analysis of alkyl polyglycoside (APG) surfactants by MALDI-MS and ESI-MS, MS/MS, and by combining MS and with ion mobility (IM) and/or ultra-performance liquid chromatography (UPLC) separation in LC-IM and LC-IM-MS experiments. Chapter VII summaries this dissertation's findings.

Transfer of Wire Arc-Sprayed Metal Coatings onto Plastic Parts

NASA Astrophysics Data System (ADS)

Bobzin, K.; Öte, M.; Knoch, M. A.; Liao, X.; Hopmann, Ch.; Ochotta, P.

2018-01-01

By means of In-Mold-Metal-Spraying (IMMS), metal coatings deposited by means of arc spraying process (ASP) can be transferred onto plastic parts during injection molding, thus realizing an efficient production of metallized plastic parts. Parts produced by means of IMMS can be used in electrical applications. In the current study, the electrical resistivity of coatings applied with different feedstock materials was determined. As a starting point, pressurized air is used as atomizing gas for ASP. In contrast to Zn coatings, Cu coatings applied with pressurized air exhibit a significantly higher electrical resistivity in comparison with massive material. One possible reason is the more pronounced oxidation of Cu particles during ASP. Therefore, N2 and a mixture of N2 and H2 were used as atomizing gas. As a result, the electrical resistivity of coatings applied by means of IMMS could be significantly reduced. Furthermore, standoff distance, current and pressure of the atomizing gas were varied to investigate the influence of these process parameters on the electrical resistivity of Zn coatings using a full factorial experiment design with center point. It can be observed that the electrical resistivity of the Zn coatings increases with decreasing current and increasing standoff distance and pressure.

Transfer of Wire Arc-Sprayed Metal Coatings onto Plastic Parts

NASA Astrophysics Data System (ADS)

Bobzin, K.; Öte, M.; Knoch, M. A.; Liao, X.; Hopmann, Ch.; Ochotta, P.

2017-12-01

By means of In-Mold-Metal-Spraying (IMMS), metal coatings deposited by means of arc spraying process (ASP) can be transferred onto plastic parts during injection molding, thus realizing an efficient production of metallized plastic parts. Parts produced by means of IMMS can be used in electrical applications. In the current study, the electrical resistivity of coatings applied with different feedstock materials was determined. As a starting point, pressurized air is used as atomizing gas for ASP. In contrast to Zn coatings, Cu coatings applied with pressurized air exhibit a significantly higher electrical resistivity in comparison with massive material. One possible reason is the more pronounced oxidation of Cu particles during ASP. Therefore, N2 and a mixture of N2 and H2 were used as atomizing gas. As a result, the electrical resistivity of coatings applied by means of IMMS could be significantly reduced. Furthermore, standoff distance, current and pressure of the atomizing gas were varied to investigate the influence of these process parameters on the electrical resistivity of Zn coatings using a full factorial experiment design with center point. It can be observed that the electrical resistivity of the Zn coatings increases with decreasing current and increasing standoff distance and pressure.

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

PubMed Central

Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​ PMID:26870619

Comparison of Combat Gauze and TraumaStat in Two Severe Groin Injury Models

DTIC Science & Technology

2011-07-01

especially given their similarity in form to stan· dard gauze currently in use . Recently, two such prod· ucts, Combat Gauze (CBG) and TraumaStat (TMS...if acted upon imme- diately after injury. With proper compression on the wound site, use of adequate hemostatic dressing for bleeding control...be minimized. In an effort for better hemo- static control in noncompressible areas such as the neck or the groin where tourniquets cannot be used

Inhibiting and Remodeling Toxic Amyloid-Beta Oligomer Formation Using a Computationally Designed Drug Molecule That Targets Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Downey, Matthew A.; Giammona, Maxwell J.; Lang, Christian A.; Buratto, Steven K.; Singh, Ambuj; Bowers, Michael T.

2018-04-01

Alzheimer's disease (AD) is rapidly reaching epidemic status among a burgeoning aging population. Much evidence suggests the toxicity of this amyloid disease is most influenced by the formation of soluble oligomeric forms of amyloid β-protein, particularly the 42-residue alloform (Aβ42). Developing potential therapeutics in a directed, streamlined approach to treating this disease is necessary. Here we utilize the joint pharmacophore space (JPS) model to design a new molecule [AC0107] incorporating structural characteristics of known Aβ inhibitors, blood-brain barrier permeability, and limited toxicity. To test the molecule's efficacy experimentally, we employed ion mobility mass spectrometry (IM-MS) to discover [AC0107] inhibits the formation of the toxic Aβ42 dodecamer at both high (1:10) and equimolar concentrations of inhibitor. Atomic force microscopy (AFM) experiments reveal that [AC0107] prevents further aggregation of Aβ42, destabilizes preformed fibrils, and reverses Aβ42 aggregation. This trend continues for long-term interaction times of 2 days until only small aggregates remain with virtually no fibrils or higher order oligomers surviving. Pairing JPS with IM-MS and AFM presents a powerful and effective first step for AD drug development.

Charge Mediated Compaction and Rearrangement of Gas-Phase Proteins: A Case Study Considering Two Proteins at Opposing Ends of the Structure-Disorder Continuum

NASA Astrophysics Data System (ADS)

Jhingree, Jacquelyn R.; Bellina, Bruno; Pacholarz, Kamila J.; Barran, Perdita E.

2017-07-01

Charge reduction in the gas phase provides a direct means of manipulating protein charge state, and when coupled to ion mobility mass spectrometry (IM-MS), it is possible to monitor the effect of charge on protein conformation in the absence of solution. Use of the electron transfer reagent 1,3-dicyanobenzene, coupled with IM-MS, allows us to monitor the effect of charge reduction on the conformation of two proteins deliberately chosen from opposite sides of the order to disorder continuum: bovine pancreatic trypsin inhibitor (BPTI) and beta casein. The ordered BPTI presents compact conformers for each of three charge states accompanied by narrow collision cross-section distributions (TWCCSDN2→He). Upon reduction of BPTI, irrespective of precursor charge state, the TWCCSN2→He decreases to a similar distribution as found for the nESI generated ion of identical charge. The behavior of beta casein upon charge reduction is more complex. It presents over a wide charge state range (9-28), and intermediate charge states (13-18) have broad TWCCSDN2→He with multiple conformations, where both compaction and rearrangement are seen. Further, we see that the TWCCSDN2→He of the latter charge states are even affected by the presence of radical anions. Overall, we conclude that the flexible nature of some proteins result in broad conformational distributions comprised of many families, even for single charge states, and the barrier between different states can be easily overcome by an alteration of the net charge.

Probabilistic Modeling of the Renal Stone Formation Module

NASA Technical Reports Server (NTRS)

Best, Lauren M.; Myers, Jerry G.; Goodenow, Debra A.; McRae, Michael P.; Jackson, Travis C.

2013-01-01

The Integrated Medical Model (IMM) is a probabilistic tool, used in mission planning decision making and medical systems risk assessments. The IMM project maintains a database of over 80 medical conditions that could occur during a spaceflight, documenting an incidence rate and end case scenarios for each. In some cases, where observational data are insufficient to adequately define the inflight medical risk, the IMM utilizes external probabilistic modules to model and estimate the event likelihoods. One such medical event of interest is an unpassed renal stone. Due to a high salt diet and high concentrations of calcium in the blood (due to bone depletion caused by unloading in the microgravity environment) astronauts are at a considerable elevated risk for developing renal calculi (nephrolithiasis) while in space. Lack of observed incidences of nephrolithiasis has led HRP to initiate the development of the Renal Stone Formation Module (RSFM) to create a probabilistic simulator capable of estimating the likelihood of symptomatic renal stone presentation in astronauts on exploration missions. The model consists of two major parts. The first is the probabilistic component, which utilizes probability distributions to assess the range of urine electrolyte parameters and a multivariate regression to transform estimated crystal density and size distributions to the likelihood of the presentation of nephrolithiasis symptoms. The second is a deterministic physical and chemical model of renal stone growth in the kidney developed by Kassemi et al. The probabilistic component of the renal stone model couples the input probability distributions describing the urine chemistry, astronaut physiology, and system parameters with the physical and chemical outputs and inputs to the deterministic stone growth model. These two parts of the model are necessary to capture the uncertainty in the likelihood estimate. The model will be driven by Monte Carlo simulations, continuously randomly sampling the probability distributions of the electrolyte concentrations and system parameters that are inputs into the deterministic model. The total urine chemistry concentrations are used to determine the urine chemistry activity using the Joint Expert Speciation System (JESS), a biochemistry model. Information used from JESS is then fed into the deterministic growth model. Outputs from JESS and the deterministic model are passed back to the probabilistic model where a multivariate regression is used to assess the likelihood of a stone forming and the likelihood of a stone requiring clinical intervention. The parameters used to determine to quantify these risks include: relative supersaturation (RS) of calcium oxalate, citrate/calcium ratio, crystal number density, total urine volume, pH, magnesium excretion, maximum stone width, and ureteral location. Methods and Validation: The RSFM is designed to perform a Monte Carlo simulation to generate probability distributions of clinically significant renal stones, as well as provide an associated uncertainty in the estimate. Initially, early versions will be used to test integration of the components and assess component validation and verification (V&V), with later versions used to address questions regarding design reference mission scenarios. Once integrated with the deterministic component, the credibility assessment of the integrated model will follow NASA STD 7009 requirements.

Capacity of wild-type and chemokine-armed parvovirus H-1PV for inhibiting neo-angiogenesis

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

Lavie, Muriel; Struyf, Sofie; Stroh-Dege, Alexandra

2013-12-15

Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumormore » growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors. - Highlights: • The oncolytic parvovirus H-1PV can target endothelial cells. • Abortive viral cycle upon infection of endothelial cells with H-1PV. • Inhibition of VEGF expression and KS-IMM tumor growth by H-1PV.« less

Guinea pigs inbred for studies of respiratory anaphylaxis.

PubMed

Lundberg, L

1979-02-01

A selective inbreeding of approximately 24 generations of albino guinea pigs by brother x sister mating has resulted in two strains, registered IMM/S and IMM/R, with high and low responsiveness, respectively, to ovalbumin-induced respiratory anaphylaxis. The two guinea pig strains differed in their ability to be immunized by the inhalation of antigen and produce antibodies, as well as to develop respiratory anaphylaxis. A correlation between the strength of the anaphylactic reactions and the amount of hemagglutinating antibodies produced was observed. When immunization was carried out by an intradermal injection of ovalbumin (OA), even in small doses incorporated in FCA, guinea pigs from both strains produced hemagglutinating antibodies in nearly the same amount. These antibodies do not influence the ability of the animals to react with a high respectively low anaphylactic response on subsequent challenge by inhalation of OA, neither in the actively sensitized animals nor in passively sensitized animals. However, with repeated inhalations of OA, desensitization occurred in the intradermally immunized high-responders, while the passively immunized high-responders could be provoked several times without any signs of desensitization. No systematical differences between the two strains with regard to sensitivity to inhalations of histamine were demonstrated. The low responders were found to be less resistant to infections than high-responders.

Mitochondrial pyruvate transport: a historical perspective and future research directions

PubMed Central

McCommis, Kyle S.; Finck, Brian N.

2015-01-01

Pyruvate is the end-product of glycolysis, a major substrate for oxidative metabolism, and a branching point for glucose, lactate, fatty acid and amino acid synthesis. The mitochondrial enzymes that metabolize pyruvate are physically separated from cytosolic pyruvate pools and rely on a membrane transport system to shuttle pyruvate across the impermeable inner mitochondrial membrane (IMM). Despite long-standing acceptance that transport of pyruvate into the mitochondrial matrix by a carrier-mediated process is required for the bulk of its metabolism, it has taken almost 40 years to determine the molecular identity of an IMM pyruvate carrier. Our current understanding is that two proteins, mitochondrial pyruvate carriers MPC1 and MPC2, form a hetero-oligomeric complex in the IMM to facilitate pyruvate transport. This step is required for mitochondrial pyruvate oxidation and carboxylation – critical reactions in intermediary metabolism that are dysregulated in several common diseases. The identification of these transporter constituents opens the door to the identification of novel compounds that modulate MPC activity, with potential utility for treating diabetes, cardiovascular disease, cancer, neurodegenerative diseases, and other common causes of morbidity and mortality. The purpose of the present review is to detail the historical, current and future research investigations concerning mitochondrial pyruvate transport, and discuss the possible consequences of altered pyruvate transport in various metabolic tissues. PMID:25748677

National Differences in Remission of Type 2 Diabetes Mellitus After Roux-en-Y Gastric Bypass Surgery-Subgroup Analysis of 2-Year Results of the Diabetes Surgery Study Comparing Taiwanese with Americans with Mild Obesity (BMI 30-35 kg/m2).

PubMed

Chong, Keong; Ikramuddin, Sayeed; Lee, Wei-Jei; Billington, Charles J; Bantle, John P; Wang, Qi; Thomas, Avis J; Connett, John E; Leslie, Daniel B; Inabnet, William B; Jeffery, Robert W; Sarr, Michael G; Jensen, Michael D; Vella, Adrian; Ahmed, Leaque; Belani, Kumar; Schone, Joyce L; Olofson, Amy E; Bainbridge, Heather A; Laqua, Patricia S; Korner, Judith; Chuang, Lee-Ming

2017-05-01

The purpose of this study is to compare effects of different nations on Roux-en-Y gastric bypass (RYGB) vs. intensive medical management (IMM) in achieving remission of type 2 diabetes mellitus (T2DM). Between April 2008 and December 2011, this randomized, controlled clinical trial was conducted at four teaching hospitals in the United States and Taiwan involving 71 participants with mild obesity (BMI 30-35 kg/m 2 ). Thirty-six of 71 participants were randomly assigned to the RYGB group, and the others were in IMM group. Partial or complete remission of T2DM was defined as blood HbA1c < 6.5 % (48 mmol/mol) or <6 % (42 mmol/mol) without any antihyperglycemic medication for at least 1-year duration, respectively. At baseline, Taiwanese participants had a lower BMI, younger age, and shorter duration of T2DM than American participants. At 24 months, weight loss was greater in the RYGB group in both populations than in the IMM group. No IMM participant of either population had partial or complete remission of T2DM. In the RYGB group, a substantial proportion of the subjects achieved complete or partial remission (57 % in Taiwanese and 27 % in American participants, P = 0.08). Logistic regression revealed stimulated C-peptide (Odds ratio 2.22, P = 0.02) but not nationality as a significant predictor of diabetes remission. Adding RYGB to lifestyle and medical management was associated with a greater likelihood of remission of T2DM in both Taiwanese and American subjects with mild obesity with type 2 diabetes. Residual beta-cell function at baseline appears to be the major factor predicting remission of T2DM. Trial registry number: clinicaltrials.gov Identifier: NCT00641251.

Transformational Solar Array Final Report

NASA Technical Reports Server (NTRS)

Gaddy, Edward; Ballarotto, Mihaela; Drabenstadt, Christian; Nichols, John; Douglas, Mark; Spence, Brian; Stall, Richard A.; Sulyma, Chris; Sharps, Paul

2017-01-01

We have made outstanding progress in the Base Phase towards achieving the final NASA Research Announcement (NRA) goals. Progress is better than anticipated due to the lighter than predicted mass of the IMM solar cells. We look forward to further improvements in the IMM cell performance during Option I and Option II; so, we have confidence that the first four items listed in the table will improve to better than the NRA goals. The computation of the end of life blanket efficiency is uncertain because we have extrapolated the radiation damage from room temperature measurements. The last three items listed in the Table were not intended to be accomplished during the Base Phase; they will be achieved during Option I and Option II.

Experimental and Theoretical Investigation of Sodiated Multimers of Steroid Epimers with Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Chouinard, Christopher D.; Cruzeiro, Vinícius Wilian D.; Roitberg, Adrian E.; Yost, Richard A.

2017-02-01

Ion mobility-mass spectrometry (IM-MS) has recently seen increased use in the analysis of small molecules, especially in the field of metabolomics, for increased breadth of information and improved separation of isomers. In this study, steroid epimers androsterone and trans-androsterone were analyzed with IM-MS to investigate differences in their relative mobilities. Although sodiated monomers exhibited very similar collision cross-sections (CCS), baseline separation was observed for the sodiated dimer species (RS = 1.81), with measured CCS of 242.6 and 256.3 Å2, respectively. Theoretical modeling was performed to determine the most energetically stable structures of solution-phase and gas-phase monomer and dimer structures. It was revealed that these epimers differ in their preferred dimer binding mode in solution phase: androsterone adopts a R=O - Na+ - OH—R' configuration, whereas trans-androsterone adopts a R=O - Na+ - O=R' configuration. This difference contributes to a significant structural variation, and subsequent CCS calculations based on these structures relaxed in the gas phase were in agreement with experimentally measured values (ΔCCS 5%). Additionally, these calculations accurately predicted the relative difference in mobility between the epimers. This study illustrates the power of combining experimental and theoretical results to better elucidate gas-phase structures.

Effect of charge on the conformation of highly basic peptides including the tail regions of histone proteins by ion mobility mass spectrometry.

PubMed

Akashi, Satoko; Downard, Kevin M

2016-09-01

The first systematic and comprehensive study of the charging behaviour and effect of charge on the conformation of specifically constructed arginine-rich peptides and its significance to the N- and C-terminal basic tail regions of histone proteins was conducted using ion mobility mass spectrometry (IM-MS). Among the basic amino acids, arginine has the greatest impact on the charging behaviour and structures of gas phase ions by virtue of its high proton affinity. A close linear correlation was found between either the maximum charge, or most abundant charge state, that the peptides support and their average collision cross section (CCS) values measured by ion mobility mass spectrometry. The calculated collision cross sections for the lowest energy solution state models predicted by the PEP-FOLD algorithm using a modified MOBCAL trajectory method were found to best correlate with the values measured by IM-MS. In the case of the histone peptides, more compact folded structures, supporting less than the maximum number of charges, were observed. These results are consistent with those previously reported for histone dimers where neutralization of the charge at the basic residues of the tail regions did not affect their CCS values.

Flood predictions using the parallel version of distributed numerical physical rainfall-runoff model TOPKAPI

NASA Astrophysics Data System (ADS)

Boyko, Oleksiy; Zheleznyak, Mark

2015-04-01

The original numerical code TOPKAPI-IMMS of the distributed rainfall-runoff model TOPKAPI ( Todini et al, 1996-2014) is developed and implemented in Ukraine. The parallel version of the code has been developed recently to be used on multiprocessors systems - multicore/processors PC and clusters. Algorithm is based on binary-tree decomposition of the watershed for the balancing of the amount of computation for all processors/cores. Message passing interface (MPI) protocol is used as a parallel computing framework. The numerical efficiency of the parallelization algorithms is demonstrated for the case studies for the flood predictions of the mountain watersheds of the Ukrainian Carpathian regions. The modeling results is compared with the predictions based on the lumped parameters models.

Optimizing Medical Kits for Space Flight

NASA Technical Reports Server (NTRS)

Minard, Charles G.; FreiredeCarvalho, Mary H.; Iyengar, M. Sriram

2010-01-01

The Integrated Medical Model (IMM) uses Monte Carlo methodologies to predict the occurrence of medical events, their mitigation, and the resources required during space flight. The model includes two modules that utilize output from a single model simulation to identify an optimized medical kit for a specified mission scenario. This poster describes two flexible optimization routines built into SAS 9.1. The first routine utilizes a systematic process of elimination to maximize (or minimize) outcomes subject to attribute constraints. The second routine uses a search and mutate approach to minimize medical kit attributes given a set of outcome constraints. There are currently 273 unique resources identified that are used to treat at least one of 83 medical conditions currently in the model.

Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5.

PubMed

Scott, Daniel; Layfield, Robert; Oldham, Neil J

2015-08-01

Many proteins exhibit conformation flexibility as part of their biological function, whether through the presence of a series of well-defined states or by the existence of intrinsic disorder. Ion mobility spectrometry, in combination with MS (IM-MS), offers a rapid and sensitive means of probing ensembles of protein structures through measurement of gas-phase collisional cross sections. We have applied IM-MS analysis to the multidomain deubiquitinating enzyme ubiquitin specific protease 5 (USP5), which is believed to exhibit significant conformational flexibility. Native ESI-MS measurement of the 94-kDa USP5 revealed two distinct charge-state distributions: [M + 17H](+) to [M + 21H](+) and [M + 24H](+) to [M + 29H](+). The collisional cross sections of these ions revealed clear groupings of 52 ± 4 nm(2) for the lower charges and 66 ± 6 nm(2) for the higher charges. Molecular dynamics simulation of a compact form of USP5, based on a crystal structure, produced structures of 53-54 nm(2) following 2 ns in the gas phase, while simulation of an extended form (based on small-angle X-ray scattering data) led to structures of 64 nm(2). These data demonstrate that IM-MS is a valuable tool in studying proteins with different discrete conformational states. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simple Motor Control Concept Results High Efficiency at High Velocities

NASA Astrophysics Data System (ADS)

Starin, Scott; Engel, Chris

2013-09-01

The need for high velocity motors in space applications for reaction wheels and detectors has stressed the limits of Brushless Permanent Magnet Motors (BPMM). Due to inherent hysteresis core losses, conventional BPMMs try to balance the need for torque verses hysteresis losses. Cong-less motors have significantly less hysteresis losses but suffer from lower efficiencies. Additionally, the inherent low inductance in cog-less motors result in high ripple currents or high switching frequencies, which lowers overall efficiency and increases performance demands on the control electronics.However, using a somewhat forgotten but fully qualified technology of Isotropic Magnet Motors (IMM), extremely high velocities may be achieved at low power input using conventional drive electronics. This paper will discuss the trade study efforts and empirical test data on a 34,000 RPM IMM.

Individual medication management system (IMMS) as a proposition of obeying the doctor's recommendation with pharmacist cooperation.

PubMed

Waszyk-Nowaczyk, Magdalena; Simon, Marek; Matwij, Karolina

2012-01-01

The pharmacist is an expert with the knowledge of drugs, who has a possibility to follow the patient's individual pharmacotherapy, which is the basis of the pharmaceutical care programme. The implementation of the Individual Medication Management System (IMMS) may be one of the proposals which will enable an analysis of the course of pharmacotherapy and elimination of drug problems, which are the chief goals of pharmaceutical care. In order to determine community pharmacy patients' degree of interest in the IMMS and to evaluate the degree of patients' discipline concerning the application of doctors' recommendations they were given an anonymous questionnaire. The research was done from August 2009 to May 2010 on a sample of 179 people selected at random. They were patients of community pharmacies in Poznań, where 70% were women and 30% were men, all of them aged between 20 and 85 years. The individual age groups were: 20-40 years--27.0%, 41-50 years--10.8%, 51-64 years--43.6%, 65 years or more--18.6%. The patients' education was as follows: primary--4.7%, vocational--8.0%, secondary--31.0%, incomplete university--12.0% and university--44.3%. The chi2 and Fisher-Freeman-Halton tests were used for statistical analysis of the results. Each time the level of statistical significance was assumed at p < 0.05. The collected results confirmed the fact that there is a higher number of specialists involved in patients' treatment with their age (p = 0.001), which indirectly leads to a higher number of prescribed drugs (p = 0.00000002). It was proved that more than 90% of the patients aged over 50 years take the prescribed drugs for more than a year (p = 0.00000002). The analysis confirmed the fact that there are mostly men which do not abide the indications concerning the dosage regimen (p = 0.049). The answers to the questions evaluating the patients' attitude to the IMMS revealed that 47.2% of the respondents indicate the advantages of the system. However, it was mostly women and respondents with university education that were the most interested in it. More than 50% of the patients aged 20-40 years and those aged over 65 years indicate the purposefulness of the systems. It is mainly the group aged 20-40 years that confirms facilitation in following the doctor's recommendations (p = 0.02). The respondents indicated their interest and confirmed the purposefulness of the IMMS mainly due to the fact that it helps to avoid drug-related problems resulting from omitting doses and helps to keep the dosage time and frequency in a long-term therapy. The research confirms the fact that individualized therapy will contribute to its higher efficacy, economy and safety.

77 FR 33640 - International Service Change-Timor-Leste

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

... Manual (IMM[supreg]), to reflect Timor-Leste's independence from Indonesia, and its joining the Universal... current listing for ``East Timor (Indonesia)'' to read ``East Timor (Timor-Leste)''. In addition insert a...

Generic framework for vessel detection and tracking based on distributed marine radar image data

NASA Astrophysics Data System (ADS)

Siegert, Gregor; Hoth, Julian; Banyś, Paweł; Heymann, Frank

2018-04-01

Situation awareness is understood as a key requirement for safe and secure shipping at sea. The primary sensor for maritime situation assessment is still the radar, with the AIS being introduced as supplemental service only. In this article, we present a framework to assess the current situation picture based on marine radar image processing. Essentially, the framework comprises a centralized IMM-JPDA multi-target tracker in combination with a fully automated scheme for track management, i.e., target acquisition and track depletion. This tracker is conditioned on measurements extracted from radar images. To gain a more robust and complete situation picture, we are exploiting the aspect angle diversity of multiple marine radars, by fusing them a priori to the tracking process. Due to the generic structure of the proposed framework, different techniques for radar image processing can be implemented and compared, namely the BLOB detector and SExtractor. The overall framework performance in terms of multi-target state estimation will be compared for both methods based on a dedicated measurement campaign in the Baltic Sea with multiple static and mobile targets given.

Small-molecule intramimics of formin autoinhibition: a new strategy to target the cytoskeletal remodeling machinery in cancer cells.

PubMed

Lash, L Leanne; Wallar, Bradley J; Turner, Julie D; Vroegop, Steven M; Kilkuskie, Robert E; Kitchen-Goosen, Susan M; Xu, H Eric; Alberts, Arthur S

2013-11-15

Although the cancer cell cytoskeleton is a clinically validated target, few new strategies have emerged for selectively targeting cell division by modulating the cytoskeletal structure, particularly ways that could avoid the cardiotoxic and neurotoxic effects of current agents such as taxanes. We address this gap by describing a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics. In screening for DID-DAD disruptors that activate mDia, we identified two molecules called intramimics (IMM-01 and -02) that were sufficient to trigger actin assembly and microtubule stabilization, serum response factor-mediated gene expression, cell-cycle arrest, and apoptosis. In vivo analysis of IMM-01 and -02 established their ability to slow tumor growth in a mouse xenograft model of colon cancer. Taken together, our work establishes the use of intramimics and mDia-related formins as a new general strategy for therapeutic targeting of the cytoskeletal remodeling machinery of cancer cells. ©2013 AACR

Demonstration of a neural circuit critical for imprinting behavior in chicks.

PubMed

Nakamori, Tomoharu; Sato, Katsushige; Atoji, Yasuro; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2010-03-24

Imprinting behavior in birds is elicited by visual and/or auditory cues. It has been demonstrated previously that visual cues are recognized and processed in the visual Wulst (VW), and imprinting memory is stored in the intermediate medial mesopallium (IMM) of the telencephalon. Alteration of neural responses in these two regions according to imprinting has been reported, yet direct evidence of the neural circuit linking these two regions is lacking. Thus, it remains unclear how memory is formed and expressed in this circuit. Here, we present anatomical as well as physiological evidence of the neural circuit connecting the VW and IMM and show that imprinting training during the critical period strengthens and refines this circuit. A functional connection established by imprint training resulted in an imprinting behavior. After the closure of the critical period, training could not activate this circuit nor induce the imprinting behavior. Glutamatergic neurons in the ventroposterior region of the VW, the core region of the hyperpallium densocellulare (HDCo), sent their axons to the periventricular part of the HD, just dorsal and afferent to the IMM. We found that the HDCo is important in imprinting behavior. The refinement and/or enhancement of this neural circuit are attributed to increased activity of HDCo cells, and the activity depended on NR2B-containing NMDA receptors. These findings show a neural connection in the telencephalon in Aves and demonstrate that NR2B function is indispensable for the plasticity of HDCo cells, which are key mediators of imprinting.

Calcium binding and transport by coenzyme Q.

PubMed

Bogeski, Ivan; Gulaboski, Rubin; Kappl, Reinhard; Mirceski, Valentin; Stefova, Marina; Petreska, Jasmina; Hoth, Markus

2011-06-22

Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV-vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography-mass spectrometry (HPLC-MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca(2+) across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca(2+) and redox homeostasis.

Effect of moisture on typical Virginia surface treatment materials.

DOT National Transportation Integrated Search

1970-01-01

Several aspects of the stripping and whip off characteristics of typical Virginia surface treatment materials were investigated. Sixty different binder-aggregate combinations were tested with the AASHO Designation T182-57 stripping test, a plate imme...

Isothermogravimetric determination of the enthalpies of vaporization of 1-alkyl-3-methylimidazolium ionic liquids.

PubMed

Luo, Huimin; Baker, Gary A; Dai, Sheng

2008-08-21

Vaporization enthalpies for two series of ionic liquids (ILs) composed of 1- n-alkyl-3-methylimidazolium cations, [Imm1+] (m=2, 3, 4, 6, 8, or 10), paired with either the bis(trifluoromethanesulfonyl)amide, [Tf2N-], or the bis(perfluoroethylsulfonyl)amide anion, [beti-], were determined using a simple, convenient, and highly reproducible thermogravimetric approach, and from these values, Hildebrand solubility parameters were estimated. Our results reveal two interesting and unanticipated outcomes: (i) methylation at the C2 position of [Imm1+] affords a significantly higher vaporization enthalpy; (ii) in all cases, the [beti-] anion served to lower the enthalpy of vaporization relative to [Tf2N-]. The widespread availability of the apparatus required for these measurements coupled with the ease of automation suggests the broad potential of this methodology for determining this critical parameter in a multitude of ILs.

Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers.

PubMed

Boschmans, Jasper; Jacobs, Sam; Williams, Jonathan P; Palmer, Martin; Richardson, Keith; Giles, Kevin; Lapthorn, Cris; Herrebout, Wouter A; Lemière, Filip; Sobott, Frank

2016-06-20

Electrospray ion mobility-mass spectrometry (IM-MS) data show that for some small molecules, two (or even more) ions with identical sum formula and mass, but distinct drift times are observed. In spite of showing their own unique and characteristic fragmentation spectra in MS/MS, no configurational or constitutional isomers are found to be present in solution. Instead the observation and separation of such ions appears to be inherent to their gas-phase behaviour during ion mobility experiments. The origin of multiple drift times is thought to be the result of protonation site isomers ('protomers'). Although some important properties of protomers have been highlighted by other studies, correlating the experimental collision cross-sections (CCSs) with calculated values has proven to be a major difficulty. As a model, this study uses the pharmaceutical compound melphalan and a number of related molecules with alternative (gas-phase) protonation sites. Our study combines density functional theory (DFT) calculations with modified MobCal methods (e.g. nitrogen-based Trajectory Method algorithm) for the calculation of theoretical CCS values. Calculated structures can be linked to experimentally observed signals, and a strong correlation is found between the difference of the calculated dipole moments of the protomer pairs and their experimental CCS separation.

Insights from native mass spectrometry approaches for top- and middle- level characterization of site-specific antibody-drug conjugates

PubMed Central

Botzanowski, Thomas; Erb, Stéphane; Hernandez-Alba, Oscar; Ehkirch, Anthony; Colas, Olivier; Wagner-Rousset, Elsa; Rabuka, David; Beck, Alain; Drake, Penelope M.; Cianférani, Sarah

2017-01-01

ABSTRACT Antibody-drug conjugates (ADCs) have emerged as a family of compounds with promise as efficient immunotherapies. First-generation ADCs were generated mostly via reactions on either lysine side-chain amines or cysteine thiol groups after reduction of the interchain disulfide bonds, resulting in heterogeneous populations with a variable number of drug loads per antibody. To control the position and the number of drug loads, new conjugation strategies aiming at the generation of more homogeneous site-specific conjugates have been developed. We report here the first multi-level characterization of a site-specific ADC by state-of-the-art mass spectrometry (MS) methods, including native MS and its hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS methodologies for site-specific ADC analysis, with the unique ability to provide several critical quality attributes within one single run, along with a direct snapshot of ADC homogeneity/heterogeneity without extensive data interpretation. The capabilities of native IM-MS to directly access site-specific ADC conformational information are also highlighted. Finally, the potential of these techniques for assessing an ADC's heterogeneity/homogeneity is illustrated by comparing the analytical characterization of a site-specific DAR4 ADC to that of first-generation ADCs. Altogether, our results highlight the compatibility, versatility, and benefits of native MS approaches for the analytical characterization of all types of ADCs, including site-specific conjugates. Thus, we envision integrating native MS and IM-MS approaches, even in their latest state-of-the-art forms, into workflows that benchmark bioconjugation strategies. PMID:28406343

Application of ion mobility-mass spectrometry to microRNA analysis.

PubMed

Takebayashi, Kosuke; Hirose, Kenji; Izumi, Yoshihiro; Bamba, Takeshi; Fukusaki, Eiichiro

2013-03-01

Liquid chromatography/mass spectrometry is widely used for studying sequence determination and modification analysis of small RNAs. However, the efficiency of liquid chromatography-based separation of intact small RNA species is insufficient, since the physiochemical properties among small RNAs are very similar. In this study, we focused on ion mobility-mass spectrometry (IM-MS), which is a gas-phase separation technique coupled with mass spectrometry; we have evaluated the utility of IM-MS for microRNA (miRNA) analysis. A multiply charged deprotonated ion derived from an 18-24-nt-long miRNA was formed by electrospray ionization, and then the time, called the "drift time", taken by each ion to migrate through a buffer gas was measured. Each multivalent ion was temporally separated on the basis of the charge state and structural formation; 3 types of unique mass-mobility correlation patterns (i.e., chainlike-form, hairpin-form, and dimer-form) were present on the two-dimensional mobility-mass spectrum. Moreover, we found that the ion size (sequence length) and the secondary structures of the small RNAs strongly contributed to the IM-MS-based separation, although solvent conditions such as pH had no effect. Therefore, sequence isomers could also be discerned by the selection of each specific charged ion, i.e., the 6(-) charged ion reflected a majority among chainlike-, hairpin-, and other structures. We concluded that the IM-MS provides additional capability for separation; thus, this analytical method will be a powerful tool for comprehensive small RNA analysis. Copyright © 2012. Published by Elsevier B.V.

Motivation in computer-assisted instruction.

PubMed

Hu, Amanda; Shewokis, Patricia A; Ting, Kimberly; Fung, Kevin

2016-08-01

Computer-aided instruction (CAI) is defined as instruction in which computers play a central role as the means of information delivery and direct interaction with learners. Computer-aided instruction has become mainstream in medical school curricula. For example, a three-dimensional (3D) computer module of the larynx has been created to teach laryngeal anatomy. Although the novelty and educational potential of CAI has garnered much attention, these new technologies have been plagued with low utilization rates. Several experts attribute this problem to lack of motivation in students. Motivation is defined as the desire and action toward goal-oriented behavior. Psychologist Dr. John Keller developed the ARCS theory of motivational learning, which proposed four components: attention (A), relevance (R), concentration (C), and satisfaction (S). Keller believed that motivation is not only an innate characteristic of the pupil; it can also be influenced by external factors, such as the instructional design of the curriculum. Thus, understanding motivation is an important step to designing CAI appropriately. Keller also developed a 36-item validated instrument called the Instructional Materials Motivation Survey (IMMS) to measure motivation. The objective of this study was to study motivation in CAI. Medical students learning anatomy with the 3D computer module will have higher laryngeal anatomy test scores and higher IMMS motivation scores. Higher anatomy test scores will be positively associated with higher IMMS scores. Prospective, randomized, controlled trial. After obtaining institutional review board approval, 100 medical students (mean age 25.5 ± 2.5, 49% male) were randomized to either the 3D computer module (n = 49) or written text (n = 51). Information content was identical in both arms. Students were given 30 minutes to study laryngeal anatomy and then completed the laryngeal anatomy test and IMMS. Students were categorized as either junior (year 1 and 2) or senior (year 3 and 4). There were no significant differences in anatomy scores based on educational modality. There was significant interaction of educational modality by year [F(1,96) = 4.12, P = 0.045, ω(2)  = 0.031]. For the total score, there was a significant effect of year [F(1,96) = 22.28, P < 0.001, ω(2)  = 0.178], with seniors (15.4 ± 2.6) scoring significantly higher than juniors (12.8 ± 3.1). For the motivational score, the total IMMS score had two significant effects. With educational modality [F(1,96) = 5.18, P = 0.025, ω(2)  = 0.041], the 3D group (12.4 ± 2.8) scored significantly higher than the written text group (11.7 ± 3.2). With year [F(1,96) = 25.31, P < 0.001, ω(2)  = 0.198], seniors (13.4 ± 3.0) scored significantly higher than juniors (10.8 ± 2.5). Pearson's correlation showed positive associations (r = 0.22-0.91) between anatomy scores and IMMS motivation scores (P < 0.05). Computer-aided instruction conferred no measurable educational benefit over traditional written text in medical students; however, CAI was associated with higher motivational levels. Computer-aided instruction was found to have a greater positive impact on senior medical students with higher anatomy and motivational scores. Higher anatomy scores were positively associated with higher motivational scores. Computer-aided instruction may be better targeted toward senior students. N/A. Laryngoscope, 126:S5-S13, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Noise Rating Criteria for Elevated Rapid Transit Structures

DOT National Transportation Integrated Search

1980-05-01

The purpose of this report is to recommend criteria for rating the noise radiated from elevated rapid transit structures during train passages, so that different types of structures can be inter-compared with respect to their noise impact on the imme...

Prohibitin (PHB) roles in granulosa cell physiology

PubMed Central

Chowdhury, Indrajit; Thomas, Kelwyn; Thompson, Winston E.

2015-01-01

Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on the recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/prohibitin/flotillin/HflK/C (SPFH) domain [also known as the PHB domain] found in divergent species from prokaryotes to eukaryotes. PHB is ubiquitously expressed either in circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane (IMM), and form complexes with the ATPases Associated with diverse cellular Activities (m-AAA) proteases. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulate transcriptional activity directly or through interactions with chromatin remodeling proteins. Multiple functions have been attributed to the mitochondrial and nuclear prohibitin complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintaining the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood. PMID:26496733

Improved estimation of sediment source contributions by concentration-dependent Bayesian isotopic mixing model

NASA Astrophysics Data System (ADS)

Ram Upadhayay, Hari; Bodé, Samuel; Griepentrog, Marco; Bajracharya, Roshan Man; Blake, Will; Cornelis, Wim; Boeckx, Pascal

2017-04-01

The implementation of compound-specific stable isotope (CSSI) analyses of biotracers (e.g. fatty acids, FAs) as constraints on sediment-source contributions has become increasingly relevant to understand the origin of sediments in catchments. The CSSI fingerprinting of sediment utilizes CSSI signature of biotracer as input in an isotopic mixing model (IMM) to apportion source soil contributions. So far source studies relied on the linear mixing assumptions of CSSI signature of sources to the sediment without accounting for potential effects of source biotracer concentration. Here we evaluated the effect of FAs concentration in sources on the accuracy of source contribution estimations in artificial soil mixture of three well-separated land use sources. Soil samples from land use sources were mixed to create three groups of artificial mixture with known source contributions. Sources and artificial mixture were analysed for δ13C of FAs using gas chromatography-combustion-isotope ratio mass spectrometry. The source contributions to the mixture were estimated using with and without concentration-dependent MixSIAR, a Bayesian isotopic mixing model. The concentration-dependent MixSIAR provided the closest estimates to the known artificial mixture source contributions (mean absolute error, MAE = 10.9%, and standard error, SE = 1.4%). In contrast, the concentration-independent MixSIAR with post mixing correction of tracer proportions based on aggregated concentration of FAs of sources biased the source contributions (MAE = 22.0%, SE = 3.4%). This study highlights the importance of accounting the potential effect of a source FA concentration for isotopic mixing in sediments that adds realisms to mixing model and allows more accurate estimates of contributions of sources to the mixture. The potential influence of FA concentration on CSSI signature of sediments is an important underlying factor that determines whether the isotopic signature of a given source is observable even after equilibrium. Therefore inclusion of FA concentrations of the sources in the IMM formulation is standard procedure for accurate estimation of source contributions. The post model correction approach that dominates the CSSI fingerprinting causes bias, especially if the FAs concentration of sources differs substantially.

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells.

PubMed

Boudousquie, Caroline; Bossi, Giovanna; Hurst, Jacob M; Rygiel, Karolina A; Jakobsen, Bent K; Hassan, Namir J

2017-11-01

The success of immune system-based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilizing monoclonal T cell receptors (TCRs) against cancer (ImmTAC™ molecules: fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv antibody) were previously shown to redirect CD8 + and CD4 + T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognizing a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8 + and CD4 + repertoires. Using isolated subpopulations of T cells, we find that both terminally differentiated and effector memory CD8 + T cells redirected by IMCgp100 are potent killers of melanoma cells. Furthermore, CD4 + effector memory T cells elicit potent cytotoxic activity leading to melanoma cell killing upon redirection by IMCgp100. The majority of T cell subsets belonging to both the CD8 + and CD4 + repertoires secrete key pro-inflammatory cytokines (tumour necrosis factor-α, interferon-γ, interleukin-6) and chemokines (macrophage inflammatory protein-1α-β, interferon-γ-inducible protein-10, monocyte chemoattractant protein-1). At an individual cell level, IMCgp100-redirected T cells display a polyfunctional phenotype, which is a hallmark of a potent anti-cancer response. This study demonstrates that IMCgp100 induces broad immune responses that extend beyond the induction of CD8 + T cell-mediated cytotoxicity. These findings are of particular importance because IMCgp100 is currently undergoing clinical trials as a single agent or in combination with check point inhibitors for patients with malignant melanoma. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

Generation and Radiation of Acoustic Waves from a 2-D Shear Layer

NASA Technical Reports Server (NTRS)

Agarwal, Anurag; Morris, Philip J.

2000-01-01

A parallel numerical simulation of the radiation of sound from an acoustic source inside a 2-D jet is presented in this paper. This basic benchmark problem is used as a test case for scattering problems that are presently being solved by using the Impedance Mismatch Method (IMM). In this technique, a solid body in the domain is represented by setting the acoustic impedance of each medium, encountered by a wave, to a different value. This impedance discrepancy results in reflected and scattered waves with appropriate amplitudes. The great advantage of the use of this method is that no modifications to a simple Cartesian grid need to be made for complicated geometry bodies. Thus, high order finite difference schemes may be applied simply to all parts of the domain. In the IMM, the total perturbation field is split into incident and scattered fields. The incident pressure is assumed to be known and the equivalent sources for the scattered field are associated with the presence of the scattering body (through the impedance mismatch) and the propagation of the incident field through a non-uniform flow. An earlier version of the technique could only handle uniform flow in the vicinity of the source and at the outflow boundary. Scattering problems in non-uniform mean flow are of great practical importance (for example, scattering from a high lift device in a non-uniform mean flow or the effects of a fuselage boundary layer). The solution to this benchmark problem, which has an acoustic wave propagating through a non-uniform mean flow, serves as a test case for the extensions of the IMM technique.

Distance geometry protocol to generate conformations of natural products to structurally interpret ion mobility-mass spectrometry collision cross sections.

PubMed

Stow, Sarah M; Goodwin, Cody R; Kliman, Michal; Bachmann, Brian O; McLean, John A; Lybrand, Terry P

2014-12-04

Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data.

Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

PubMed Central

2015-01-01

Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data. PMID:25360896

Strategic Positioning and Biased Activity of the Mitochondrial Calcium Uniporter in Cardiac Muscle*

PubMed Central

De La Fuente, Sergio; Fernandez-Sanz, Celia; Vail, Caitlin; Agra, Elorm J.; Holmstrom, Kira; Sun, Junhui; Mishra, Jyotsna; Williams, Dewight; Finkel, Toren; Murphy, Elizabeth; Joseph, Suresh K.; Sheu, Shey-Shing; Csordás, György

2016-01-01

Control of myocardial energetics by Ca2+ signal propagation to the mitochondrial matrix includes local Ca2+ delivery from sarcoplasmic reticulum (SR) ryanodine receptors (RyR2) to the inner mitochondrial membrane (IMM) Ca2+ uniporter (mtCU). mtCU activity in cardiac mitochondria is relatively low, whereas the IMM surface is large, due to extensive cristae folding. Hence, stochastically distributed mtCU may not suffice to support local Ca2+ transfer. We hypothesized that mtCU concentrated at mitochondria-SR associations would promote the effective Ca2+ transfer. mtCU distribution was determined by tracking MCU and EMRE, the proteins essential for channel formation. Both proteins were enriched in the IMM-outer mitochondrial membrane (OMM) contact point submitochondrial fraction and, as super-resolution microscopy revealed, located more to the mitochondrial periphery (inner boundary membrane) than inside the cristae, indicating high accessibility to cytosol-derived Ca2+ inputs. Furthermore, MCU immunofluorescence distribution was biased toward the mitochondria-SR interface (RyR2), and this bias was promoted by Ca2+ signaling activity in intact cardiomyocytes. The SR fraction of heart homogenate contains mitochondria with extensive SR associations, and these mitochondria are highly enriched in EMRE. Size exclusion chromatography suggested for EMRE- and MCU-containing complexes a wide size range and also revealed MCU-containing complexes devoid of EMRE (thus disabled) in the mitochondrial but not the SR fraction. Functional measurements suggested more effective mtCU-mediated Ca2+ uptake activity by the mitochondria of the SR than of the mitochondrial fraction. Thus, mtCU “hot spots” can be formed at the cardiac muscle mitochondria-SR associations via localization and assembly bias, serving local Ca2+ signaling and the excitation-energetics coupling. PMID:27637331

A chemometric approach for characterization of serum transthyretin in familial amyloidotic polyneuropathy type I (FAP-I) by electrospray ionization-ion mobility mass spectrometry.

PubMed

Pont, Laura; Sanz-Nebot, Victoria; Vilaseca, Marta; Jaumot, Joaquim; Tauler, Roma; Benavente, Fernando

2018-05-01

In this study, we describe a chemometric data analysis approach to assist in the interpretation of the complex datasets from the analysis of high-molecular mass oligomeric proteins by ion mobility mass spectrometry (IM-MS). The homotetrameric protein transthyretin (TTR) is involved in familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR(Met30)) that can be easily detected analyzing the monomeric forms of the mutant protein. However, the mechanism of protein misfolding and aggregation onset, which could be triggered by structural changes in the native tetrameric protein, remains under investigation. Serum TTR from healthy controls and FAP-I patients was purified under non-denaturing conditions by conventional immunoprecipitation in solution and analyzed by IM-MS. IM-MS allowed separation and characterization of several tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time. After an appropriate data pre-processing, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the complex datasets. A group of seven independent components being characterized by their ion mobility profiles and mass spectra were resolved to explain the observed data variance in control and patient samples. Then, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were considered for exploration and classification. Only four out of the seven resolved components were enough for an accurate differentiation. Furthermore, the specific TTR ions identified in the mass spectra of these components and the resolved ion mobility profiles provided a straightforward insight into the most relevant oligomeric TTR proteoforms for the disease. Copyright © 2018 Elsevier B.V. All rights reserved.

78 FR 63433 - International Mailing Services: Proposed Price Changes-CPI

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... POSTAL SERVICE 39 CFR Part 20 International Mailing Services: Proposed Price Changes--CPI AGENCY... mailing services price adjustments with the Postal Regulatory Commission (PRC), effective on January 26... Postal Service, International Mail Manual (IMM[supreg]) to reflect these new price changes. DATES: We...

78 FR 63434 - International Mailing Services: Proposed Price Changes-Exigent

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... POSTAL SERVICE 39 CFR Part 20 International Mailing Services: Proposed Price Changes--Exigent... notice of mailing services price adjustments with the Postal Regulatory Commission (PRC), effective on... United States Postal Service, International Mail Manual (IMM[supreg]) to reflect these new price changes...

The effects of in-vehicle and infrastructure-based collision warnings at signalized intersections

DOT National Transportation Integrated Search

2009-12-01

The potential effectiveness of warnings to drivers of the imminent threat of a collision with a red light violator was evaluated in an experiment that used a driving simulator. Three warnings were tested: (1) an infrastructure-based warning that imme...

RImmPort: an R/Bioconductor package that enables ready-for-analysis immunology research data.

PubMed

Shankar, Ravi D; Bhattacharya, Sanchita; Jujjavarapu, Chethan; Andorf, Sandra; Wiser, Jeffery A; Butte, Atul J

2017-04-01

: Open access to raw clinical and molecular data related to immunological studies has created a tremendous opportunity for data-driven science. We have developed RImmPort that prepares NIAID-funded research study datasets in ImmPort (immport.org) for analysis in R. RImmPort comprises of three main components: (i) a specification of R classes that encapsulate study data, (ii) foundational methods to load data of a specific study and (iii) generic methods to slice and dice data across different dimensions in one or more studies. Furthermore, RImmPort supports open formalisms, such as CDISC standards on the open source bioinformatics platform Bioconductor, to ensure that ImmPort curated study datasets are seamlessly accessible and ready for analysis, thus enabling innovative bioinformatics research in immunology. RImmPort is available as part of Bioconductor (bioconductor.org/packages/RImmPort). rshankar@stanford.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing

NASA Astrophysics Data System (ADS)

Both, P.; Green, A. P.; Gray, C. J.; Šardzík, R.; Voglmeir, J.; Fontana, C.; Austeri, M.; Rejzek, M.; Richardson, D.; Field, R. A.; Widmalm, G.; Flitsch, S. L.; Eyers, C. E.

2014-01-01

Mass spectrometry is the primary analytical technique used to characterize the complex oligosaccharides that decorate cell surfaces. Monosaccharide building blocks are often simple epimers, which when combined produce diastereomeric glycoconjugates indistinguishable by mass spectrometry. Structure elucidation frequently relies on assumptions that biosynthetic pathways are highly conserved. Here, we show that biosynthetic enzymes can display unexpected promiscuity, with human glycosyltransferase pp-α-GanT2 able to utilize both uridine diphosphate N-acetylglucosamine and uridine diphosphate N-acetylgalactosamine, leading to the synthesis of epimeric glycopeptides in vitro. Ion-mobility mass spectrometry (IM-MS) was used to separate these structures and, significantly, enabled characterization of the attached glycan based on the drift times of the monosaccharide product ions generated following collision-induced dissociation. Finally, ion-mobility mass spectrometry following fragmentation was used to determine the nature of both the reducing and non-reducing glycans of a series of epimeric disaccharides and the branched pentasaccharide Man3 glycan, demonstrating that this technique may prove useful for the sequencing of complex oligosaccharides.

Capacity of wild-type and chemokine-armed parvovirus H-1PV for inhibiting neo-angiogenesis.

PubMed

Lavie, Muriel; Struyf, Sofie; Stroh-Dege, Alexandra; Rommelaere, Jean; Van Damme, Jo; Dinsart, Christiane

2013-12-01

Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumor growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors. © 2013 Elsevier Inc. All rights reserved.

Estimated Probability of a Cervical Spine Injury During an ISS Mission

NASA Technical Reports Server (NTRS)

Brooker, John E.; Weaver, Aaron S.; Myers, Jerry G.

2013-01-01

Introduction: The Integrated Medical Model (IMM) utilizes historical data, cohort data, and external simulations as input factors to provide estimates of crew health, resource utilization and mission outcomes. The Cervical Spine Injury Module (CSIM) is an external simulation designed to provide the IMM with parameter estimates for 1) a probability distribution function (PDF) of the incidence rate, 2) the mean incidence rate, and 3) the standard deviation associated with the mean resulting from injury/trauma of the neck. Methods: An injury mechanism based on an idealized low-velocity blunt impact to the superior posterior thorax of an ISS crewmember was used as the simulated mission environment. As a result of this impact, the cervical spine is inertially loaded from the mass of the head producing an extension-flexion motion deforming the soft tissues of the neck. A multibody biomechanical model was developed to estimate the kinematic and dynamic response of the head-neck system from a prescribed acceleration profile. Logistic regression was performed on a dataset containing AIS1 soft tissue neck injuries from rear-end automobile collisions with published Neck Injury Criterion values producing an injury transfer function (ITF). An injury event scenario (IES) was constructed such that crew 1 is moving through a primary or standard translation path transferring large volume equipment impacting stationary crew 2. The incidence rate for this IES was estimated from in-flight data and used to calculate the probability of occurrence. The uncertainty in the model input factors were estimated from representative datasets and expressed in terms of probability distributions. A Monte Carlo Method utilizing simple random sampling was employed to propagate both aleatory and epistemic uncertain factors. Scatterplots and partial correlation coefficients (PCC) were generated to determine input factor sensitivity. CSIM was developed in the SimMechanics/Simulink environment with a Monte Carlo wrapper (MATLAB) used to integrate the components of the module. Results: The probability of generating an AIS1 soft tissue neck injury from the extension/flexion motion induced by a low-velocity blunt impact to the superior posterior thorax was fitted with a lognormal PDF with mean 0.26409, standard deviation 0.11353, standard error of mean 0.00114, and 95% confidence interval [0.26186, 0.26631]. Combining the probability of an AIS1 injury with the probability of IES occurrence was fitted with a Johnson SI PDF with mean 0.02772, standard deviation 0.02012, standard error of mean 0.00020, and 95% confidence interval [0.02733, 0.02812]. The input factor sensitivity analysis in descending order was IES incidence rate, ITF regression coefficient 1, impactor initial velocity, ITF regression coefficient 2, and all others (equipment mass, crew 1 body mass, crew 2 body mass) insignificant. Verification and Validation (V&V): The IMM V&V, based upon NASA STD 7009, was implemented which included an assessment of the data sets used to build CSIM. The documentation maintained includes source code comments and a technical report. The software code and documentation is under Subversion configuration management. Kinematic validation was performed by comparing the biomechanical model output to established corridors.

Pharmacologic Effects on Mitochondrial Function

ERIC Educational Resources Information Center

Cohen, Bruce H.

2010-01-01

The vast majority of energy necessary for cellular function is produced in mitochondria. Free-radical production and apoptosis are other critical mitochondrial functions. The complex structure, electrochemical properties of the inner mitochondrial membrane (IMM), and genetic control from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) are…

76 FR 50414 - International Mail Manual; Incorporation by Reference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... POSTAL SERVICE 39 CFR Part 20 International Mail Manual; Incorporation by Reference AGENCY: Postal... Standards of the United States Postal Service, International Mail Manual (IMM[supreg]) dated April 17, 2011.... SUPPLEMENTARY INFORMATION: The International Mail Manual was issued on April 17, 2011, and was updated with...

75 FR 34017 - International Mail Manual; Incorporation by Reference

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... POSTAL SERVICE 39 CFR Part 20 International Mail Manual; Incorporation by Reference AGENCY: Postal... Mailing Standards of the United States Postal Service, International Mail Manual (IMM[supreg]) and its..., (202) 268-3789. SUPPLEMENTARY INFORMATION: Issue 36 of the International Mail Manual was issued on May...

Determination of Polychlorinated Biphenyls in Soil and Sediment by Selective Pressurized Liquid Extraction with Immunochemical Detection

EPA Science Inventory

A selective liquid pressurized extraction (SPLE) method was developed as a streamlined sample preparation/cleanup procedure for determining Aroclors and coplanar polychlorinated biphenyls (PCBs) in soil and sediment matrices. The SPLE method was coupled with an enzyme-linked imm...

77 FR 12724 - International Postal Service-Global Expedited Package Services (GEPS) Contracts

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... POSTAL SERVICE\\TM\\ 39 CFR Part 20 International Postal Service--Global Expedited Package Services (GEPS) Contracts AGENCY: Postal Service TM . ACTION: Final rule. SUMMARY: The Postal Service will revise Mailing Standards of the United States Postal Service, International Mail Manual (IMM[supreg]) to...

Effect of 2 herbal intramammary products on milk quantity and quality compared with conventional and no dry cow therapy.

PubMed

Mullen, K A E; Anderson, K L; Washburn, S P

2014-01-01

Dry cow therapy, administered at the end of lactation, is aimed at eliminating current and preventing future intramammary (IMM) bacterial infections and typically involves intramammary administration of antibiotics. Certified organic dairies in the United States are restricted from using antibiotics and must consider an alternative therapy or no dry cow therapy. The current study compared 2 herbal products to conventional dry cow therapy and no treatment for a total of 5 treatments over 2 trials. Trial 1 was conducted over 3 yr on 1 research farm and trial 2 included 4 commercial farms plus the research herd over 2 yr. Treatments included (1) a conventional IMM antibiotic and internal teat sealant (penicillin-dihydrostreptomycin and bismuth subnitrate; CON); (2) an herbal IMM product purported to act as a teat sealant (Cinnatube, New AgriTech Enterprises, Locke, NY; CIN); (3) an herbal IMM product (Phyto-Mast, Bovinity Health LLC, Narvon, PA; P-M); (4) Phyto-Mast and Cinnatube (PC); or (5) no dry cow therapy (NT). Each treatment group was balanced by breed, lactation number, due date, herd, and year. However, the CON treatment was used only in the research herd because of the intent to avoid antibiotic usage on the other 4 farms. Comparisons among treatments included the difference between pre- and posttreatment 305-d mature equivalent milk production (trial 1), somatic cell score change from dry-off to freshening at the cow and quarter levels (trials 1 and 2), and milk microbiology change over the dry period (trial 2). We detected no significant differences among treatments for milk yield differences between the lactation following treatment and the lactation preceding treatment. Changes in somatic cell score from one lactation to the next also did not differ significantly among treatments in either trial. Cure rates were not significantly different among treatments; only 19.6% of all quarters were infected at dry off. The proportion of quarters with new infections at 3 to 5d postcalving did not significantly differ among treatments, except between CIN and NT. Percentages (least squares means ± standard error) of quarters with new infections were 24 ± 21% for CON, 15 ± 7% for CIN, 30 ± 10% for P-M, 32 ± 11% for PC, and 35 ± 11% for NT. The efficacy of the herbal products was similar to that of conventional therapy, and the herbal products had no apparent adverse effects. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.

PubMed

Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2015-08-01

Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. © 2015 The Protein Society.

High-Concentration III-V Multijunction Solar Cells | Photovoltaic Research

Science.gov Websites

| NREL High-Concentration III-V Multijunction Solar Cells High-Concentration III-V transfer to the high-efficiency cell industry, and the invention and development of the inverted metamorphic multijunction (IMM) cell technology. PV Research Other Materials & Devices pages: High

MERCURY IN CRUDE OIL PROCESSED IN THE UNITED STATES (2004)

EPA Science Inventory

The mean and range of concentrations of mercury in crude oil processed in the U.S. were investigated using two analytical methods. The sample ensemble consisted of 329 samples from 170 separate crude oil streams that are processed by U.S. refineries. Samples were retrieved imme...

76 FR 7114 - International Mail: Mailing Services Price Change

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

... POSTAL SERVICE 39 CFR Part 20 International Mail: Mailing Services Price Change AGENCY: Postal... States Postal Service, International Mail Manual (IMM[supreg]) for Mailing Services. This price change correlates to the Postal Service's January 13, 2011 filing of Docket No. R2011-2, Notice of Price Adjustment...

77 FR 64724 - International Mail Manual; Incorporation by Reference

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... POSTAL SERVICE 39 CFR Part 20 International Mail Manual; Incorporation by Reference AGENCY: Postal... Standards of the United States Postal Service, International Mail Manual (IMM[supreg]) dated June 24, 2012... International Mail Manual was issued on June 24, 2012, and was updated with postal bulletin revisions through...

Interactive Multimedia: Practice and Promise.

ERIC Educational Resources Information Center

Latchem, Colin, Ed.; And Others

This book describes developments in interactive multimedia (IMM) in the early 1990s. Its aim is to provide educators, students, trainers, librarians, managers, and practitioners with an overview, not only of the directions and uses of the technology, but also of the research foundations and educational and contextual issues that need to be…

Conjugation-Mediated Transfer of Antibiotic-Resistance Plasmids Between Enterobacteriaceae in the Digestive Tract of Blaberus craniifer (Blattodea: Blaberidae).

PubMed

Anacarso, I; Iseppi, R; Sabia, C; Messi, P; Condò, C; Bondi, M; de Niederhäusern, S

2016-05-01

Cockroaches, insects of the order Blattodea, seem to play a crucial role in the possible conjugation-mediated genetic exchanges that occur among bacteria that harbor in the cockroach intestinal tract. The gut of these insects can be thought of as an effective in vivo model for the natural transfer of antimicrobial resistance plasmids among bacteria. In our study, we evaluated the conjugation-mediated horizontal transfer of resistance genes between Escherichia coli and other microorganisms of the same Enterobacteriaceae family within the intestinal tract of Blaberus craniifer Burmeister, 1838 (Blattodea: Blaberidae). Different in vivo mating experiments were performed using E. coli RP4 harboring the RP4 plasmid carrying ampicillin, kanamycin, and tetracycline resistance genes as the donor and E. coli K12 resistant to nalidixic acid or Salmonella enterica serovar Enteritidis IMM39 resistant to streptomycin as the recipients. The RP4 plasmid was successfully transferred to both recipients, producing E. coli K12-RP4 and S. Enteritidis IMM39-RP4 transconjugants. Conjugation frequencies in vivo were similar to those previously observed in vitro. The transfer of the RP4 plasmid in all transconjugants was confirmed by small-scale plasmid isolation and agar gel electrophoresis, suggesting that the intestinal tract of cockroaches is an effective in vivo model for natural gene transfer. Our results confirm that cockroaches allow for the exchange of antimicrobial resistance plasmids among bacteria and may represent a potential reservoir for the dissemination of antibiotic-resistant bacteria in different environments. These findings are particularly significant to human health in the context of health care settings such as hospitals. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Getting to Outcomes: A Best Practice Process to Help Schools Achieve Desired Outcomes

ERIC Educational Resources Information Center

Maras, Melissa A.; Wandersman, Abe; Splett, Joni Williams; Flaspohler, Paul; Weist, Mark

2012-01-01

This article describes Getting to Outcomes (GTO), a 10-step framework for accountability designed to facilitate effective implementation of evidence-based programs and improvement of home-grown practices (Getting to Outcomes and GTO are trademarks registered by the University of South Carolina and RAND; Wandersman, Imm, Chinman, & Kaftarian,…

NREL Inks Technology Agreement for High Efficiency Multijunction Solar

Science.gov Websites

) multijunction solar cells. While high-efficiency multijunction solar cells are commonly used for space Devices is excited to now be commercializing IMM solar cells for high-performance space and UAV Cells | News | NREL Inks Technology Agreement for High Efficiency Multijunction Solar Cells

Medical Surveillance Monthly Report. Volume 19, Number 7

DTIC Science & Technology

2012-07-01

education for recruits at acces- sion. While the Marine Corps and...other Services. This may reflect that most servicewomen receive chlamydia screening, treatment and education imme- diately upon accession, while... hemoglobin , the substance in red blood cells (RBCs) that carries oxygen from the lungs to the rest of the body. In the face of

The Developer's Handbook to Interactive Multimedia: A Practical Guide for Educational Applications.

ERIC Educational Resources Information Center

Phillips, Rob

Interactive multimedia (IMM) is a technology with the potential to change the way people learn, acquire information, and entertain themselves. This technology brings together a range of fields and requires the skills of professionals from those fields. This handbook offers practical advice on issues related to developing successful interactive…

A Collaborative Decision Environment for UAV Operations

NASA Technical Reports Server (NTRS)

D'Ortenzio, Matthew V.; Enomoto, Francis Y.; Johan, Sandra L.

2005-01-01

NASA is developing Intelligent Mission Management (IMM) technology for science missions employing long endurance unmanned aerial vehicles (UAV's). The IMM groundbased component is the Collaborative Decision Environment (CDE), a ground system that provides the Mission/Science team with situational awareness, collaboration, and decisionmaking tools. The CDE is used for pre-flight planning, mission monitoring, and visualization of acquired data. It integrates external data products used for planning and executing a mission, such as weather, satellite data products, and topographic maps by leveraging established and emerging Open Geospatial Consortium (OGC) standards to acquire external data products via the Internet, and an industry standard geographic information system (GIs) toolkit for visualization As a Science/Mission team may be geographically dispersed, the CDE is capable of providing access to remote users across wide area networks using Web Services technology. A prototype CDE is being developed for an instrument checkout flight on a manned aircraft in the fall of 2005, in preparation for a full deployment in support of the US Forest Service and NASA Ames Western States Fire Mission in 2006.

Aerosol Vacuum-Assisted Plasma Ionization (Aero-VaPI) Coupled to Ion Mobility-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Blair, Sandra L.; Ng, Nga L.; Zambrzycki, Stephen C.; Li, Anyin; Fernández, Facundo M.

2018-02-01

In this communication, we report on the real-time analysis of organic aerosol particles by Vacuum-assisted Plasma Ionization-Mass Spectrometry (Aero-VaPI-MS) using a home-built VaPI ion source coupled to a Synapt G2-S HDMS ion mobility-mass spectrometry (IM-MS) system. Standards of organic molecules of interest in prebiotic chemistry were used to generate aerosols. Monocaprin and decanoic acid aerosol particles were successfully detected in both the positive and negative ion modes, respectively. A complex aerosol mixture of different sizes of polymers of L-malic acid was also examined through ion mobility (IM) separations, resulting in the detection of polymers of up to eight monomeric units. This noncommercial plasma ion source is proposed as a low cost alternative to other plasma ionization platforms used for aerosol analysis, and a higher-performance alternative to more traditional aerosol mass spectrometers. VaPI provides robust online ionization of organics in aerosols without extensive ion activation, with the coupling to IM-MS providing higher peak capacity and excellent mass accuracy. [Figure not available: see fulltext.

Uncovering the stoichiometry of Pyrococcus furiosus RNase P, a multi-subunit catalytic ribonucleoprotein complex, by surface-induced dissociation and ion mobility mass spectrometry.

PubMed

Ma, Xin; Lai, Lien B; Lai, Stella M; Tanimoto, Akiko; Foster, Mark P; Wysocki, Vicki H; Gopalan, Venkat

2014-10-20

We demonstrate that surface-induced dissociation (SID) coupled with ion mobility mass spectrometry (IM-MS) is a powerful tool for determining the stoichiometry of a multi-subunit ribonucleoprotein (RNP) complex assembled in a solution containing Mg(2+). We investigated Pyrococcus furiosus (Pfu) RNase P, an archaeal RNP that catalyzes tRNA 5' maturation. Previous step-wise, Mg(2+)-dependent reconstitutions of Pfu RNase P with its catalytic RNA subunit and two interacting protein cofactor pairs (RPP21⋅RPP29 and POP5⋅RPP30) revealed functional RNP intermediates en route to the RNase P enzyme, but provided no information on subunit stoichiometry. Our native MS studies with the proteins showed RPP21⋅RPP29 and (POP5⋅RPP30)2 complexes, but indicated a 1:1 composition for all subunits when either one or both protein complexes bind the cognate RNA. These results highlight the utility of SID and IM-MS in resolving conformational heterogeneity and yielding insights on RNP assembly. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

cea-kil operon of the ColE1 plasmid.

PubMed Central

Sabik, J F; Suit, J L; Luria, S E

1983-01-01

We isolated a series of Tn5 transposon insertion mutants and chemically induced mutants with mutations in the region of the ColE1 plasmid that includes the cea (colicin) and imm (immunity) genes. Bacterial cells harboring each of the mutant plasmids were tested for their response to the colicin-inducing agent mitomycin C. All insertion mutations within the cea gene failed to bring about cell killing after mitomycin C treatment. A cea- amber mutation exerted a polar effect on killing by mitomycin C. Two insertions beyond the cea gene but within or near the imm gene also prevented the lethal response to mitomycin C. These findings suggest the presence in the ColE1 plasmid of an operon containing the cea and kil genes whose product is needed for mitomycin C-induced lethality. Bacteria carrying ColE1 plasmids with Tn5 inserted within the cea gene produced serologically cross-reacting fragments of the colicin E1 molecule, the lengths of which were proportional to the distance between the insertion and the promoter end of the cea gene. Images PMID:6298187

Recovery after chronic stress within spatial reference and working memory domains: correspondence with hippocampal morphology.

PubMed

Hoffman, A N; Krigbaum, A; Ortiz, J B; Mika, A; Hutchinson, K M; Bimonte-Nelson, H A; Conrad, C D

2011-09-01

Chronic stress results in reversible spatial learning impairments in the Morris water maze that correspond with hippocampal CA3 dendritic retraction in male rats. Whether chronic stress impacts different types of memory domains, and whether these can similarly recover, is unknown. This study assessed the effects of chronic stress with and without a post-stress delay to evaluate learning and memory deficits within two memory domains, reference and working memory, in the radial arm water maze (RAWM). Three groups of 5-month-old male Sprague-Dawley rats were either not stressed [control (CON)], or restrained (6 h/day for 21 days) and then tested on the RAWM either on the next day [stress immediate (STR-IMM)] or following a 21-day delay [stress delay (STR-DEL)]. Although the groups learned the RAWM task similarly, groups differed in their 24-h retention trial assessment. Specifically, the STR-IMM group made more errors within both the spatial reference and working memory domains, and these deficits corresponded with a reduction in apical branch points and length of hippocampal CA3 dendrites. In contrast, the STR-DEL group showed significantly fewer errors in both the reference and working memory domains than the STR-IMM group. Moreover, the STR-DEL group showed better RAWM performance in the reference memory domain than did the CON group, and this corresponded with restored CA3 dendritic complexity, revealing long-term enhancing actions of chronic stress. These results indicate that chronic stress-induced spatial working and reference memory impairments, and CA3 dendritic retraction, are reversible, with chronic stress having lasting effects that can benefit spatial reference memory, but with these lasting beneficial effects being independent of CA3 dendritic complexity. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study.

PubMed

Biancone, Livia; Zuzzi, Sara; Ranieri, Micaela; Petruzziello, Carmelina; Calabrese, Emma; Onali, Sara; Ascolani, Marta; Zorzi, Francesca; Condino, Giovanna; Iacobelli, Simona; Pallone, Francesco

2012-06-01

The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Distribution and geochemistry of selected trace elements in the Sacramento River near Keswick Reservoir

USGS Publications Warehouse

Antweiler, Ronald C.; Taylor, Howard E.; Alpers, Charles N.

2012-01-01

The effect of heavy metals from the Iron Mountain Mines (IMM) Superfund site on the upper Sacramento River is examined using data from water and bed sediment samples collected during 1996-97. Relative to surrounding waters, aluminum, cadmium, cobalt, copper, iron, lead, manganese, thallium, zinc and the rare-earth elements (REE) were all present in high concentrations in effluent from Spring Creek Reservoir (SCR), which enters into the Sacramento River in the Spring Creek Arm of Keswick Reservoir. SCR was constructed in part to regulate the flow of acidic, metal-rich waters draining the IMM Superfund site. Although virtually all of these metals exist in SCR in the dissolved form, upon entering Keswick Reservoir they at least partially converted via precipitation and/or adsorption to the particulate phase. In spite of this, few of the metals settled out; instead the vast majority was transported colloidally down the Sacramento River at least to Bend Bridge, 67. km from Keswick Dam.The geochemical influence of IMM on the upper Sacramento River was variable, chiefly dependent on the flow of Spring Creek. Although the average flow of the Sacramento River at Keswick Dam is 250m 3/s (cubic meters per second), even flows as low as 0.3m 3/s from Spring Creek were sufficient to account for more than 15% of the metals loading at Bend Bridge, and these proportions increased with increasing Spring Creek flow.The dissolved proportion of the total bioavailable load was dependent on the element but steadily decreased for all metals, from near 100% in Spring Creek to values (for some elements) of less than 1% at Bend Bridge; failure to account for the suspended sediment load in assessments of the effect of metals transport in the Sacramento River can result in estimates which are low by as much as a factor of 100. ?? 2012.

Distribution and geochemistry of selected trace elements in the Sacramento River near Keswick Reservoir

USGS Publications Warehouse

Antweiler, Ronald C.; Taylor, Howard E.; Alpers, Charles N.

2012-01-01

The effect of heavy metals from the Iron Mountain Mines (IMM) Superfund site on the upper Sacramento River is examined using data from water and bed sediment samples collected during 1996-97. Relative to surrounding waters, aluminum, cadmium, cobalt, copper, iron, lead, manganese, thallium, zinc and the rare-earth elements (REE) were all present in high concentrations in effluent from Spring Creek Reservoir (SCR), which enters into the Sacramento River in the Spring Creek Arm of Keswick Reservoir. SCR was constructed in part to regulate the flow of acidic, metal-rich waters draining the IMM Superfund site. Although virtually all of these metals exist in SCR in the dissolved form, upon entering Keswick Reservoir they at least partially converted via precipitation and/or adsorption to the particulate phase. In spite of this, few of the metals settled out; instead the vast majority was transported colloidally down the Sacramento River at least to Bend Bridge, 67 km from Keswick Dam. The geochemical influence of IMM on the upper Sacramento River was variable, chiefly dependent on the flow of Spring Creek. Although the average flow of the Sacramento River at Keswick Dam is 250 m3/s (cubic meters per second), even flows as low as 0.3 m3/s from Spring Creek were sufficient to account for more than 15% of the metals loading at Bend Bridge, and these proportions increased with increasing Spring Creek flow. The dissolved proportion of the total bioavailable load was dependent on the element but steadily decreased for all metals, from near 100% in Spring Creek to values (for some elements) of less than 1% at Bend Bridge; failure to account for the suspended sediment load in assessments of the effect of metals transport in the Sacramento River can result in estimates which are low by as much as a factor of 100.

Immediate Protein Dietary Effects on Movement and the Generalised Immunocompetence of Migrating Mormon Crickets Anabrus simplex (Orthoptera: Tettigoniidae)

USDA-ARS?s Scientific Manuscript database

1. Mormon crickets form large migratory bands that march over rangeland in the western United States seeking salt and protein. Immune defense is particularly relevant to survival in migratory bands, but little is known about the role of nutrition in insect immunocompetence. We hypothesized that imm...

IMM Solar Cell Shows Its Versatility - Continuum Magazine | NREL

Science.gov Websites

. Inventing a new type of solar cell is one thing. Setting efficiency records with it and winning major awards add to the achievement. But when one of the world's leading manufacturers of compound semiconductor thin metal foil, and the substrate that the cell was grown on is removed. One advantage of this

Moving towards Inclusive French as a Second Official Language Education in Canada

ERIC Educational Resources Information Center

Mady, Callie

2013-01-01

This paper examines French as a second official language (FSOL) teachers' perspectives as they relate to the inclusion of immigrants who are learning English (IMMs), in elementary FSOL education in an English-dominant region of Canada, in particular within French immersion. In this paper, I have tried to examine the question of access to…

NREL Solar Cell Wins Federal Technology Transfer Prize | News | NREL

Science.gov Websites

Solar Cell Wins Federal Technology Transfer Prize News Release: NREL Solar Cell Wins Federal ) Solar Cell was named a winner of the 2009 Award for Excellence in Technology Transfer by the Federal Laboratory Consortium for Technology Transfer. The original IMM cell was invented by Mark Wanlass of NREL's

20180312 - Retrofitting an Estrogen Receptor Transactivation Assay with Metabolic Competence Using Alginate Immobilization of Metabolic Enzymes (AIME) (SOT)

EPA Science Inventory

The VM7Luc4E2 estrogen receptor (ER) transactivation assay is an OECD approved method (TG 457) for the detection of ER agonists and antagonists, and is also part of the Tox21 high-throughput screening (HTS) portfolio. Despite its international acceptance as a screening assay, imm...

Utilizing Generalization Tactics to Promote Leisure-Time Physical Activity for Students with Intellectual Disabilities

ERIC Educational Resources Information Center

Haegele, Justin A.; Park, Seung Yeon

2016-01-01

Research suggests that school-aged individuals with intellectual disabilities (ID) tend to be less physically active than their typically developing peers (e.g., Shields, King, Corbett, & Imms, 2014). While these students can be successful in acquiring motor and sport-related skills during physical education, they tend not to use those skills…

On the Effect of Sphere-Overlap on Super Coarse-Grained Models of Protein Assemblies

NASA Astrophysics Data System (ADS)

Degiacomi, Matteo T.

2018-05-01

Ion mobility mass spectrometry (IM/MS) can provide structural information on intact protein complexes. Such data, including connectivity and collision cross sections (CCS) of assemblies' subunits, can in turn be used as a guide to produce representative super coarse-grained models. These models are constituted by ensembles of overlapping spheres, each representing a protein subunit. A model is considered plausible if the CCS and sphere-overlap levels of its subunits fall within predetermined confidence intervals. While the first is determined by experimental error, the latter is based on a statistical analysis on a range of protein dimers. Here, we first propose a new expression to describe the overlap between two spheres. Then we analyze the effect of specific overlap cutoff choices on the precision and accuracy of super coarse-grained models. Finally, we propose a method to determine overlap cutoff levels on a per-case scenario, based on collected CCS data, and show that it can be applied to the characterization of the assembly topology of symmetrical homo-multimers. [Figure not available: see fulltext.

Architecture for Integrated Medical Model Dynamic Probabilistic Risk Assessment

NASA Technical Reports Server (NTRS)

Jaworske, D. A.; Myers, J. G.; Goodenow, D.; Young, M.; Arellano, J. D.

2016-01-01

Probabilistic Risk Assessment (PRA) is a modeling tool used to predict potential outcomes of a complex system based on a statistical understanding of many initiating events. Utilizing a Monte Carlo method, thousands of instances of the model are considered and outcomes are collected. PRA is considered static, utilizing probabilities alone to calculate outcomes. Dynamic Probabilistic Risk Assessment (dPRA) is an advanced concept where modeling predicts the outcomes of a complex system based not only on the probabilities of many initiating events, but also on a progression of dependencies brought about by progressing down a time line. Events are placed in a single time line, adding each event to a queue, as managed by a planner. Progression down the time line is guided by rules, as managed by a scheduler. The recently developed Integrated Medical Model (IMM) summarizes astronaut health as governed by the probabilities of medical events and mitigation strategies. Managing the software architecture process provides a systematic means of creating, documenting, and communicating a software design early in the development process. The software architecture process begins with establishing requirements and the design is then derived from the requirements.

Clustering of mutations within the inverted repeat regions of a serially-passaged attenuated gallid herpesvirus type 2 strain.

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is the leading cause of losses in chicken production in the world. Over the past 40 years significant progress has been made in the control of MD through the use of vaccines which reduce or delay tumor formation in vaccinated flocks. However, these vaccines fail to induce an imm...

Learning French as a Second Official Language in Canada: Comparing Monolingual and Bilingual Students at Grade 6

ERIC Educational Resources Information Center

Mady, Callie

2014-01-01

This paper presents the results of a study that compared the French as a second official achievement of three groups of students: (1) Canadian-born English speaking (CBE), (2) Canadian-born multilingual (CBM), and (3) immigrant multilinguals (IMM) as determined by multiskills test results. ANOVAs and subsequent post hoc tests revealed that the…

Pedagogical Design Considerations in Sex Education on Interactive Multimedia Using CD-Rom: An Example of Sexual Intercourse

ERIC Educational Resources Information Center

Goldman, Juliette D. G.; Torrisi-Steele, Geraldine

2005-01-01

Human sexuality is a significant issue for educators to understand and teach about, and for young people to learn about. The development of interactive multimedia technologies has added a range of new dimensions associated with designing pedagogies for sex education on Interactive Multimedia (IMM). Here, a module on CD-Rom on Sexuality and Human…

Montanide ISA 71 VG adjuvant enhances antibody and cell-ediated immune responses to profilin subunit antigen vaccination and promotes protection against Eimeria acervulina and Eimeria tenella

USDA-ARS?s Scientific Manuscript database

The present study was conducted to investigate the immunoenhancing effects of ISA 71 VG adjuvant on profilin subunit antigen vaccination. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with ISA 71 VG, and host imm...

Structural Characterization of Monomers and Oligomers of D-Amino Acid-Containing Peptides Using T-Wave Ion Mobility Mass Spectrometry

NASA Astrophysics Data System (ADS)

Pang, Xueqin; Jia, Chenxi; Chen, Zhengwei; Li, Lingjun

2017-01-01

The D-residues are crucial to biological function of D-amino acid containing peptides (DAACPs). Previous ion mobility mass spectrometry (IM-MS) studies revealing oligomerization patterns of amyloid cascade demonstrated conversion from native soluble unstructured assembly to fibril ß-sheet oligomers, which has been implicated in amyloid diseases, such as Alzheimer's disease and type 2 diabetes. Although neuropeptides are typically present at very low concentrations in circulation, their local concentrations could be much higher in large dense core vesicles, forming dimers or oligomers. We studied the oligomerization of protonated and metal-adducted achatin I and dermorphin peptide isomers with IM-MS. Our results suggested that dimerization, oligomerization, and metal adduction augment the structural differences between D/L peptide isomers compared to protonated monomers. Dimers and oligomers enhanced the structural differences between D/L peptide isomers in both aqueous and organic solvent system. Furthermore, some oligomer forms were only observed for either D- or L-isomers, indicating the importance of chiral center in oligomerization process. The oligomerization patterns of D/L isomers appear to be similar. Potassium adducts were detected to enlarge the structural differences between D/L isomers.

Fuel processing in integrated micro-structured heat-exchanger reactors

NASA Astrophysics Data System (ADS)

Kolb, G.; Schürer, J.; Tiemann, D.; Wichert, M.; Zapf, R.; Hessel, V.; Löwe, H.

Micro-structured fuel processors are under development at IMM for different fuels such as methanol, ethanol, propane/butane (LPG), gasoline and diesel. The target application are mobile, portable and small scale stationary auxiliary power units (APU) based upon fuel cell technology. The key feature of the systems is an integrated plate heat-exchanger technology which allows for the thermal integration of several functions in a single device. Steam reforming may be coupled with catalytic combustion in separate flow paths of a heat-exchanger. Reactors and complete fuel processors are tested up to the size range of 5 kW power output of a corresponding fuel cell. On top of reactor and system prototyping and testing, catalyst coatings are under development at IMM for numerous reactions such as steam reforming of LPG, ethanol and methanol, catalytic combustion of LPG and methanol, and for CO clean-up reactions, namely water-gas shift, methanation and the preferential oxidation of carbon monoxide. These catalysts are investigated in specially developed testing reactors. In selected cases 1000 h stability testing is performed on catalyst coatings at weight hourly space velocities, which are sufficiently high to meet the demands of future fuel processing reactors.

Y-12 Integrated Materials Management System

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

Alspaugh, D. H.; Hickerson, T. W.

2002-06-03

The Integrated Materials Management System, when fully implemented, will provide the Y-12 National Security Complex with advanced inventory information and analysis capabilities and enable effective assessment, forecasting and management of nuclear materials, critical non-nuclear materials, and certified supplies. These capabilities will facilitate future Y-12 stockpile management work, enhance interfaces to existing National Nuclear Security Administration (NNSA) corporate-level information systems, and enable interfaces to planned NNSA systems. In the current national nuclear defense environment where, for example, weapons testing is not permitted, material managers need better, faster, more complete information about material properties and characteristics. They now must manage non-special nuclearmore » material at the same high-level they have managed SNM, and information capabilities about both must be improved. The full automation and integration of business activities related to nuclear and non-nuclear materials that will be put into effect by the Integrated Materials Management System (IMMS) will significantly improve and streamline the process of providing vital information to Y-12 and NNSA managers. This overview looks at the kinds of information improvements targeted by the IMMS project, related issues, the proposed information architecture, and the progress to date in implementing the system.« less

The use of computer assisted technology to enhance student psychiatric nurses learning during a practice placement.

PubMed

Denny, Margaret; Higgins, Agnes

2003-06-01

Despite the available literature that identifies the value of integrating computer-assisted learning into the curriculum, psychiatric nurse education lags behind in this area of curriculum development. The purpose of this paper is to report on a pilot project involving the use of a computer assisted learning (CAL) interactive multimedia (IMM) package called 'Admissions,' as a self-directed learning tool with two-second year psychiatric nursing students. The students were on a practice placement in an Irish mental health service. The aim of using the multimedia resource was to augment the students' learning during their practice placement and enable them to re-examine the issue of psychosis from a multiplicity of perspectives. This paper provides a brief description of the interactive multimedia package, together with a discussion on the support offered to the students during its use. experiential taxonomy is used as a framework to guide the discussion on the learning and evaluation process used. Feedback from the students suggests that the CAL package is easy to use, informative and promoted independence and self-directed study.

Engineer Novel Anticancer Bioagents

DTIC Science & Technology

2009-10-01

Nonribosomally by Bacteria Gene depH is depicted as one of the three post- nonribosomal peptide synthetase (NRPS; dark red)/ polyketide synthase (PKS... polyketide synthase -NRPS pathway for FK228 biosynthesis in C. violaceum no. 968 (Cheng et al., 2007). This pathway would lead to the production of an imme...biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase. Chem. Biol. 11, 33–45

The Pathophysiology of Combined Injury and Trauma: Proceedings of the International Symposium (1st) Held at the Uniformed Services University of the Health Sciences, Bethesda, Maryland on 27-29 April 1983

DTIC Science & Technology

1983-04-29

311 antibacterial activity alone, but when used in conjunction with a beta-lactam . antibiotic, they are effective in treating infections caused by...1979) Antibacterial activity of bladder surface mucin duplicated by exogenous glycosarrino- glycan (heparin). Infect. Imm. 24:552-557. 34. Sugarman...436 Thyroid Function ................................................ 443 Catabolic Activity

Military Standard: Military Training Programs

DTIC Science & Technology

1990-12-05

Commander, Naval Sea Systems Command, SEA 55Z3, Department of the Navy, Washington, DC 20362-5101 by using the self -addressed Standardization Document...information to the trainee. 3.63 InMtructional media materials (IMM). Instructional materials that present a body of information and are largely self ...computer power and W storage in equipmnent which is self -contained (for example, videodisc player) - not necessarily part of a complt com utr system. For

Surviving the Storm : Expanding Public Health’s Capabilities in Response to the Increasing Threats Posed by Novel Viruses

DTIC Science & Technology

2013-12-01

Therapy Citations Uses Pros Cons Medical Efficacy Mono-Therapy: Class: Statins Atorvastatin (Lipitor) Rosuvastatin (Crestor) Simvastatin...Considerations Citations Good Choice for a State Stockpile? Yes or No Mono-Therapy: Statins Atorvastatin (Lipitor) ↓ Virus Rep: No ↓ Imm...www.goodrx.com/lipitor/price#/?distance=13&filter-location=&coords=&label= atorvastatin &formtablet &strength=40mg&quantity=custom&qty-custom=18450&language

Refinements in the Combined Adjustment of Satellite Altimetry and Gravity Anomaly Data

DTIC Science & Technology

1977-07-12

observations. - 151 UM Uj&liiäUäBä&immeä*,*^^ ^«^V^.^.v.rf ffM ’* ^.,/-=:jfcfe^te:^*ä*di 9.2 Spherical Harmonic Resolution The number of spherical harmonic...depend on the point mass parameters, 185 —--■ ^* p^^!?8!^ Bpp ^pg(p|SP!|p|g| we can write dr 1 dN 1 and use (9.44a). The presence of the state

Reconfigurable C2 DDP System

DTIC Science & Technology

1988-07-01

should be easily provided if the service requests can be handled simultaneously. 2.3.2 Internal Structure of Subsystems The internal structure of...Public Affairs Division (PA) and is releasable to the National Technical Information Service (NTIS). At NTIS it will be releasable to the general public...nmua n m n Imm I DISCLAIMER NOTICE THIS DOCUMENT IS BEST QUALITY PRACTICABLE. THE COPY FURNISHED TO DTIC CONTAINED A SIGNIFICANT NUMBER OF PAGES WHICH DO

Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans

PubMed Central

Viscardi, Lucas Henriques; Paixão-Côrtes, Vanessa Rodrigues; Comas, David; Salzano, Francisco Mauro; Rovaris, Diego; Bau, Claiton Dotto; Amorim, Carlos Eduardo G.; Bortolini, Maria Cátira

2018-01-01

Abstract Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans. PMID:29658973

Adsorbed States of phosphonate derivatives of N-heterocyclic aromatic compounds, imidazole, thiazole, and pyridine on colloidal silver: comparison with a silver electrode.

PubMed

Podstawka, Edyta; Olszewski, Tomasz K; Boduszek, Bogdan; Proniewicz, Leonard M

2009-09-03

Here, we report a systematic surface-enhanced Raman spectroscopy (SERS) study of the structures of phosphonate derivatives of the N-heterocyclic aromatic compounds imidazole (ImMeP ([hydroxy(1H-imidazol-5-yl)methyl]phosphonic acid) and (ImMe)(2)P (bis[hydroxy-(1H-imidazol-4-yl)-methyl]phosphinic acid)), thiazole (BAThMeP (butylaminothiazol-2-yl-methyl)phosphonic acid) and BzAThMeP (benzylaminothiazol-2-yl-methyl)phosphonic acid)), and pyridine ((PyMe)(2)P (bis[(hydroxypyridin-3-yl-methyl)]phosphinic acid)) adsorbed on nanometer-sized colloidal particles. We compared these structures to those on a roughened silver electrode surface to determine the relationship between the adsorption strength and the geometry. For example, we showed that all of these biomolecules interact with the colloidal surface through aromatic rings. However, for BzAThMeP, a preferential interaction between the benzene ring and the colloidal silver surface is observed more so than that between the thiazole ring and this substrate. The PC(OH)C fragment does not take part in the adsorption process, and the phosphonate moiety of ImMeP and (ImMe)(2)P, being removed from the surface, only assists in this process.

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™

PubMed Central

Dykstra, Andrew B.; Sweeney, Matt D.; Leary, Julie A.

2013-01-01

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions. PMID:24970196

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™.

PubMed

Dykstra, Andrew B; Sweeney, Matt D; Leary, Julie A

2013-11-06

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions.

Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics[S

PubMed Central

Hines, Kelly M.; Herron, Josi; Xu, Libin

2017-01-01

Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic-interaction liquid chromatography (HILIC) with traveling-wave IM-MS (TWIM-MS) for comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, and glycerophospholipids are separated on the basis of their lipid backbones in the IM dimension, whereas subclasses of each category are mostly separated on the basis of their headgroups in the HILIC dimension, demonstrating the orthogonality of HILIC and IM separations. Using our previously established lipid calibrants for collision cross-section (CCS) measurements in TWIM, we measured over 250 CCS values covering 12 lipid classes in positive and negative modes. The coverage of the HILIC-IM-MS method is demonstrated in the analysis of Neuro2a neuroblastoma cells exposed to benzalkonium chlorides (BACs) with C10 or C16 alkyl chains, which we have previously shown to affect gene expression related to cholesterol and lipid homeostasis. We found that BAC exposure resulted in significant changes to several lipid classes, including glycerides, sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines. Our results indicate that BAC exposure modifies lipid homeostasis in a manner that is dependent upon the length of the BAC alkyl chain. PMID:28167702

Smart Grid Interoperability Maturity Model

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

Widergren, Steven E.; Levinson, Alex; Mater, J.

2010-04-28

The integration of automation associated with electricity resources (including transmission and distribution automation and demand-side resources operated by end-users) is key to supporting greater efficiencies and incorporating variable renewable resources and electric vehicles into the power system. The integration problems faced by this community are analogous to those faced in the health industry, emergency services, and other complex communities with many stakeholders. To highlight this issue and encourage communication and the development of a smart grid interoperability community, the GridWise Architecture Council (GWAC) created an Interoperability Context-Setting Framework. This "conceptual model" has been helpful to explain the importance of organizationalmore » alignment in addition to technical and informational interface specifications for "smart grid" devices and systems. As a next step to building a community sensitive to interoperability, the GWAC is investigating an interoperability maturity model (IMM) based on work done by others to address similar circumstances. The objective is to create a tool or set of tools that encourages a culture of interoperability in this emerging community. The tools would measure status and progress, analyze gaps, and prioritize efforts to improve the situation.« less

Multimeric complexes among ankyrin-repeat and SOCS-box protein 9 (ASB9), ElonginBC, and Cullin 5: insights into the structure and assembly of ECS-type Cullin-RING E3 ubiquitin ligases.

PubMed

Thomas, Jemima C; Matak-Vinkovic, Dijana; Van Molle, Inge; Ciulli, Alessio

2013-08-06

Proteins of the ankyrin-repeat and SOCS-box (ASB) family act as the substrate-recognition subunits of ECS-type (ElonginBC-Cullin-SOCS-box) Cullin RING E3 ubiquitin ligase (CRL) complexes that catalyze the specific polyubiquitination of cellular proteins to target them for degradation by the proteasome. Therefore, ASB multimeric complexes are involved in numerous cell processes and pathways; however, their interactions, assembly, and biological roles remain poorly understood. To enhance our understanding of ASB CRL systems, we investigated the structure, affinity, and assembly of the quaternary multisubunit complex formed by ASB9, Elongin B, Elongin C (EloBC), and Cullin 5. Here, we describe the application of several biophysical techniques including differential scanning fluorimetry, isothermal titration calorimetry (ITC), nanoelectrospray ionization, and ion-mobility mass spectrometry (IM-MS) to provide structural and thermodynamic information for a quaternary ASB CRL complex. We find that ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain (Cul5NTD) but not to Cul2NTD. The structure of the monomeric ASB9-EloBC-Cul5NTD quaternary complex is revealed by molecular modeling and is consistent with IM-MS and temperature-dependent ITC data. This is the first experimental study to validate structural information for the assembly of the quaternary N-terminal region of an ASB CRL complex. The results suggest that ASB E3 ligase complexes function and assemble in an analogous manner to that of other CRL systems and provide a platform for further molecular investigation of this important protein family. The data reported here will also be of use for the future development of chemical probes to examine the biological function and modulation of other ECS-type CRL systems.

Enterprise Reference Library

NASA Technical Reports Server (NTRS)

Bickham, Grandin; Saile, Lynn; Havelka, Jacque; Fitts, Mary

2011-01-01

Introduction: Johnson Space Center (JSC) offers two extensive libraries that contain journals, research literature and electronic resources. Searching capabilities are available to those individuals residing onsite or through a librarian s search. Many individuals have rich collections of references, but no mechanisms to share reference libraries across researchers, projects, or directorates exist. Likewise, information regarding which references are provided to which individuals is not available, resulting in duplicate requests, redundant labor costs and associated copying fees. In addition, this tends to limit collaboration between colleagues and promotes the establishment of individual, unshared silos of information The Integrated Medical Model (IMM) team has utilized a centralized reference management tool during the development, test, and operational phases of this project. The Enterprise Reference Library project expands the capabilities developed for IMM to address the above issues and enhance collaboration across JSC. Method: After significant market analysis for a multi-user reference management tool, no available commercial tool was found to meet this need, so a software program was built around a commercial tool, Reference Manager 12 by The Thomson Corporation. A use case approach guided the requirements development phase. The premise of the design is that individuals use their own reference management software and export to SharePoint when their library is incorporated into the Enterprise Reference Library. This results in a searchable user-specific library application. An accompanying share folder will warehouse the electronic full-text articles, which allows the global user community to access full -text articles. Discussion: An enterprise reference library solution can provide a multidisciplinary collection of full text articles. This approach improves efficiency in obtaining and storing reference material while greatly reducing labor, purchasing and duplication costs. Most importantly, increasing collaboration across research groups provides unprecedented access to information relevant to NASA s mission. Conclusion: This project is an expansion and cost-effective leveraging of the existing JSC centralized library. Adding key word and author search capabilities and an alert function for notifications about new articles, based on users profiles, represent examples of future enhancements.

HRP's Healthcare Spin-Offs Through Computational Modeling and Simulation Practice Methodologies

NASA Technical Reports Server (NTRS)

Mulugeta, Lealem; Walton, Marlei; Nelson, Emily; Peng, Grace; Morrison, Tina; Erdemir, Ahmet; Myers, Jerry

2014-01-01

Spaceflight missions expose astronauts to novel operational and environmental conditions that pose health risks that are currently not well understood, and perhaps unanticipated. Furthermore, given the limited number of humans that have flown in long duration missions and beyond low Earth-orbit, the amount of research and clinical data necessary to predict and mitigate these health and performance risks are limited. Consequently, NASA's Human Research Program (HRP) conducts research and develops advanced methods and tools to predict, assess, and mitigate potential hazards to the health of astronauts. In this light, NASA has explored the possibility of leveraging computational modeling since the 1970s as a means to elucidate the physiologic risks of spaceflight and develop countermeasures. Since that time, substantial progress has been realized in this arena through a number of HRP funded activates such as the Digital Astronaut Project (DAP) and the Integrated Medical Model (IMM). Much of this success can be attributed to HRP's endeavor to establish rigorous verification, validation, and credibility (VV&C) processes that ensure computational models and simulations (M&S) are sufficiently credible to address issues within their intended scope. This presentation summarizes HRP's activities in credibility of modeling and simulation, in particular through its outreach to the community of modeling and simulation practitioners. METHODS: The HRP requires all M&S that can have moderate to high impact on crew health or mission success must be vetted in accordance to NASA Standard for Models and Simulations, NASA-STD-7009 (7009) [5]. As this standard mostly focuses on engineering systems, the IMM and DAP have invested substantial efforts to adapt the processes established in this standard for their application to biological M&S, which is more prevalent in human health and performance (HHP) and space biomedical research and operations [6,7]. These methods have also generated substantial interest by the broader medical community though institutions like the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) to develop similar standards and guidelines applicable to the larger medical operations and research community. DISCUSSION: Similar to NASA, many leading government agencies, health institutions and medical product developers around the world are recognizing the potential of computational M&S to support clinical research and decision making. In this light, substantial investments are being made in computational medicine and notable discoveries are being realized [8]. However, there is a lack of broadly applicable practice guidance for the development and implementation of M&S in clinical care and research in a manner that instills confidence among medical practitioners and biological researchers [9,10]. In this presentation, we will give an overview on how HRP is working with the NIH's Interagency Modeling and Analysis Group (IMAG), the FDA and the American Society of Mechanical Engineers (ASME) to leverage NASA's biomedical VV&C processes to establish a new regulatory standard for Verification and Validation in Computational Modeling of Medical Devices, and Guidelines for Credible Practice of Computational Modeling and Simulation in Healthcare.

Rapid Pipeline Repair Technology for War Damage Recovery

DTIC Science & Technology

1993-06-01

Design Manual 22, NAVFAC DM-22, Department of the Navy, Naval Facilities Engineering Command, Alexandria VA, August 1982. 2. U.S. Air Force Weapons...Inflatable Seal Over Replacement section ’"MOM Figure 10. Inflating the Seal With Manual Pump 19 Figure 11. Completed Inflatable Seal Coupler Repair 20...cumbersome repair manuals and stacks of blueprints normally used to make repairs. Since the probability of an expert being on hand imme- diately after an

EMERGING INFECTIOUS DISEASES. Actions Needed to Address the Challenges of Responding to Zika Virus Disease Outbreaks

DTIC Science & Technology

2017-05-01

Department of Health and Human Services 81 Appendix IV Zika Virus Case Definitions for National Notifiable Disease Reporting 86 Appendix V...Insecticide, Fungicide, and Rodenticide Act HHS Department of Health and Human Services IgG immunoglobulin G IgM immunoglobulin M IMM...Agency (EPA), and Department of Health and Human Services (HHS) including CDC, FDA and National Institutes of Health (NIH). We also convened, with

JPRS Report, Science & Technology, USSR: Science & Technology Policy

DTIC Science & Technology

1990-10-15

beings. They have developed various technologies of the transfer of genes from some plants to others. As a result so-called transgenic strains of...and in our country by means of the transgenic introduction of additional growth hormones giant carp and other fish have been obtained. In the imme...diate future transgenic animals can become producers of milk and wool of special quality and have resistance to diseases. PRAVDA: Is it not

Adaptable Structural Logic System Synthesis with Bistable Snap-Through Elements

DTIC Science & Technology

2012-12-01

It is well known that an unsymmetrical laminates exhibit out-of-plane displacements at room temperature even if cured flat . The unsymmetrical...various input frequencies and the loss factor of the system is evaluated. Figure VI-7: Three-cell test bed 59 \\ imm) W TELEDYNE SCIENTIFIC...design. 4- 4 Figure VI-9: Panoramic view of 10 cell test bed 60 w TELEDYNE SCIENTIFIC & IMAGING, LLC ATeledyne Technologies Company Table VI-2

Study of Modern Instrumentation and Methods for Astronomic Positioning in the Field

DTIC Science & Technology

1987-03-01

CALL AMAT(A.Y, UKK, KALPHA, DELTA) DO 40 kl.,2*K WR ITE( 3.300 )( A( I.M),.M=1,3) 300 FORMAT M, 3F18.12) 40 CONTINUE CALL BMAT (BY, UKKK, ALPHA, DELTA...1 20 CONTINUE RETURN END C C C SUBROUTINE BMAT (B, YU, KK, KALPHA, DELTA) C BMAT constructs the matrix 8 DIMENSION B(2*KK,3*KK)LY(KK,3),U(3),ALPHA(KK

Integrated Use of Planaria (Dugesia dorotocephala) and Bacillus thuringiensis var. Israelensis against Aedes Taeniorhynchus: A Laboratory Bioassay

DTIC Science & Technology

1990-12-01

predatory planarian , Dugesia dorotoce- against Ae. taeniorhynchus under phala (Woodworth), and the microbial larvicide, andplanaria ins. u Bacillus...association between B.t.i. and planaria, The opinions or assertions contained herein are and planarian consumption of B.t.i.-dosed mos- the private views of...specifically, 3 Kenk, R. 1972. Freshwater planarians [Turbellarial of species of minnows, due to 2 factors: (1) imme- North America. Biota of

Effect of Formalin Toxoiding on Pseudomonas Aeruginosa Toxin A: Biological Chemical and Immunochemical Studies

DTIC Science & Technology

1981-01-01

incubated for an additional 10 min at 22°C. Immune rene test tubes. Samples were withdrawn aseptically complexes were collected by centrifugation at 3.000... tested imme- of assay buffer, and the final pellets were counted with diately in an assay, and the other was frozen at -70°C. a Beckman Biogamma counter... tested before and after activation immunoadsorbent for immune complexes containing with urea and dithiothreitol (13). Enzyme neutraliza

Social predisposition dependent neuronal activity in the intermediate medial mesopallium of domestic chicks (Gallus gallus domesticus).

PubMed

Mayer, Uwe; Rosa-Salva, Orsola; Lorenzi, Elena; Vallortigara, Giorgio

2016-09-01

Species from phylogenetically distant animal groups, such as birds and primates including humans, share early experience-independent social predispositions that cause offspring, soon after birth, to attend to and learn about conspecifics. One example of this phenomenon is provided by the behaviour of newly-hatched visually-naïve domestic chicks that preferentially approach a stimulus resembling a conspecific (a stuffed fowl) rather than a less naturalistic object (a scrambled version of the stuffed fowl). However, the neuronal mechanisms underlying this behaviour are mostly unknown. Here we analysed chicks' brain activity with immunohistochemical detection of the transcription factor c-Fos. In a spontaneous choice test we confirmed a significant preference for approaching the stuffed fowl over a texture fowl (a fowl that was cut in small pieces attached to the sides of a box in scrambled order). Comparison of brain activation of a subgroup of chicks that approached either one or the other stimulus revealed differential activation in an area relevant for imprinting (IMM, intermediate medial mesopallium), suggesting that a different level of plasticity is associated with approach to naturalistic and artificial stimuli. c-Fos immunoreactive neurons were present also in the intermediate layers of the optic tectum (a plausible candidate for processing early social predispositions) showing a trend similar to the results for the IMM. Copyright © 2016 Elsevier B.V. All rights reserved.

[Neurobiology of imprinting].

PubMed

Ohki-Hamazaki, Hiroko

2012-06-01

Imprinting is an example of learning and memory acquisition in infancy. In the case of precocial birds, such as geese, ducks, and chickens, the baby birds learn the characteristics of the first moving object that they see within a critical period, and they imprint on it and follow it around. We analyzed the neural basis of this behavior in order to understand the neural mechanism of learning and memory in infancy. Information pertaining to a visual imprinting stimulus is recognized and processed in the visual Wulst, a region that corresponds to the mammalian visual cortex. It is then transmitted to the posterior region of the telencephalon, followed by the core region of the hyperpallium densocellulare (HDCo), periventricular region of the hyperpallium densocellulare (HDPe), and finally, the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. Memory is stored in the IMM. After imprint training, plastic changes are observed in the visual Wulst as well as in the neurons of this circuit. HDCo cells, located at the center of this circuit, express N-methyl-D-aspartate (NMDA) receptors containing the NMDA receptor (NR) 2B subunit; the expression of this receptor increased after the imprint training. Inhibition of this receptor in the cells of the HDCo region leads to failure of imprinting and inactivation of this circuit. Thus, NMDA receptors bearing the NR2B subunit play a critical role in plastic changes in this circuit and in induction of imprinting.

Frequency, predictors, and consequences of maintenance infliximab therapy intensification in ulcerative colitis.

PubMed

Fernández-Salazar, Luis; Barrio, Jesús; Muñoz, Fernando; Muñoz, Concepción; Pajares, Ramón; Rivero, Montserrat; Prieto, Vanesa; Legido, Jesús; Bouhmidi, Abdel; Herranz, Maite; González-Redondo, Guillermo; Fernández, Nereida; Santos, Fernando; Sánchez-Ocaña, Ramón; Joao, Diana

2015-09-01

Infliximab (IFX) therapy intensification in ulcerative colitis (UC) is more common than established in pivotal studies. To establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment. A retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX) induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy. Follow-up time from induction to data collection: 38 months [interquartile range (IQR), 20-62]. Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM) and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002), steroid reintroduction (35% vs. 18%; p, 0.018), and colectomy (22% vs. 6.4%; p, 0.011) were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks. Intensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predictsnon-intensification. Intensification, while effective, is associated with poorer outcome.

Precision mass measurements of magnesium isotopes and implications for the validity of the isobaric mass multiplet equation

DOE PAGES

Brodeur, M.; Kwiatkowski, A. A.; Drozdowski, O. M.; ...

2017-09-18

If the mass excess of neutron-deficient nuclei and their neutron-rich mirror partners are both known, it can be shown that deviations of the isobaric mass multiplet equation (IMME) in the form of a cubic term can be probed. Such a cubic term was probed by using the atomic mass of neutron-rich magnesium isotopes measured using the TITAN Penning trap and the recently measured proton-separation energies of 29Cl and 30Ar. The atomic mass of 27Mg was found to be within 1.6σ of the value stated in the Atomic Mass Evaluation. The atomic masses of 28,29Mg were measured to be both withinmore » 1σ, while being 7 and 33 times more precise, respectively. Using the 29Mg mass excess and previous measurements of 29Cl, we uncovered a cubic coefficient of d = 28(7)keV, which is the largest known cubic coefficient of the IMME. This departure, however, could also be caused by experimental data with unknown systematic errors. Hence there is a need to confirm the mass excess of 28S and the one-neutron separation energy of 29Cl, which have both come from a single measurement. Lastly, our results were compared with ab initio calculations from the valence-space in-medium similarity renormalization group, resulting in a good agreement.« less

Manufacturing of High-Efficiency Bi-Facial Tandem Concentrator Solar Cells: February 20, 2009--August 20, 2010

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

Wojtczuk , S.

2011-06-01

Spire Semiconductor made concentrator photovoltaic (CPV) cells using a new bi-facial growth process and met both main program goals: a) 42.5% efficiency 500X (AM1.5D, 25C, 100mW/cm2); and b) Ready to supply at least 3MW/year of such cells at end of program. We explored a unique simple fabrication process to make a N/P 3-junction InGaP/GaAs/InGaAs tandem cells . First, the InGaAs bottom cell is grown on the back of a GaAs wafer. The wafers are then loaded into a cassette, spin-rinsed to remove particles, dipped in dilute NH4OH and spin-dried. The wafers are then removed from the cassette loaded the reactormore » for GaAs middle and InGaP top cell growth on the opposite wafer face (bi-facial growth). By making the epitaxial growth process a bit more complex, we are able to avoid more complex processing (such as large area wafer bonding or epitaxial liftoff) used in the inverted metamorphic (IMM) approach to make similar tandem stacks. We believe the yield is improved compared to an IMM process. After bi-facial epigrowth, standard III-V cell steps (back metal, photolithography for front grid, cap etch, AR coat, dice) are used in the remainder of the process.« less

Contact toxicity of insecticides for attract-and-kill applications against adult Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae).

PubMed

Campos, Manuel; Phillips, Thomas W

2010-07-01

The Indian meal moth (IMM), Plodia interpunctella (Hübner), is an important pest of stored food products. Contact toxicities of 13 insecticides applied to different surfaces were evaluated at registered label and a higher dose for killing adult males. The ultimate objective was to develop attract-and-kill technologies for P. interpunctella. Two-day-old adult males were exposed to treated surfaces for 2.0 s and then paired with virgin females for mating and oviposition over a 24 h period. Permethrins and pyrethrins (organic pyrethrin and pyrethrin plus a synergist) caused over 70% mortality to males. Oviposition was impacted by these insecticides, while egg hatch was not. A second experiment tested the 8 week residual toxicity of cyfluthrin, permethrin and pyrethrin at label and at a higher dose of 20 g AI L(-1) on five surfaces: plastic-coated paper, metal, painted plastic, unpainted plastic and wood. Permethrin at 20 g AI L(-1) suppressed males at over 80% for up to 8 weeks and retained activity on surfaces made with plastic-coated paper, metal or plastic. Oviposition was variable among treatments. Egg hatch was generally unaffected by treatment. Effective attract-and-kill surfaces can be developed for killing IMM males and thereby potentially lead to reduced reproduction and, ultimately, population suppression. Copyright (c) 2010 Society of Chemical Industry.

Precision mass measurements of magnesium isotopes and implications for the validity of the isobaric mass multiplet equation

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

Brodeur, M.; Kwiatkowski, A. A.; Drozdowski, O. M.

If the mass excess of neutron-deficient nuclei and their neutron-rich mirror partners are both known, it can be shown that deviations of the isobaric mass multiplet equation (IMME) in the form of a cubic term can be probed. Such a cubic term was probed by using the atomic mass of neutron-rich magnesium isotopes measured using the TITAN Penning trap and the recently measured proton-separation energies of 29Cl and 30Ar. The atomic mass of 27Mg was found to be within 1.6σ of the value stated in the Atomic Mass Evaluation. The atomic masses of 28,29Mg were measured to be both withinmore » 1σ, while being 7 and 33 times more precise, respectively. Using the 29Mg mass excess and previous measurements of 29Cl, we uncovered a cubic coefficient of d = 28(7)keV, which is the largest known cubic coefficient of the IMME. This departure, however, could also be caused by experimental data with unknown systematic errors. Hence there is a need to confirm the mass excess of 28S and the one-neutron separation energy of 29Cl, which have both come from a single measurement. Lastly, our results were compared with ab initio calculations from the valence-space in-medium similarity renormalization group, resulting in a good agreement.« less

Mitochondria-targeted molecules determine the redness of the zebra finch bill.

PubMed

Cantarero, Alejandro; Alonso-Alvarez, Carlos

2017-10-01

The evolution and production mechanisms of red carotenoid-based ornaments in animals are poorly understood. Recently, it has been suggested that enzymes transforming yellow carotenoids to red pigments (ketolases) in animal cells may be positioned in the inner mitochondrial membrane (IMM) intimately linked to the electron transport chain. These enzymes may mostly synthesize coenzyme Q 10 (coQ 10 ), a key redox-cycler antioxidant molecularly similar to yellow carotenoids. It has been hypothesized that this shared pathway favours the evolution of red traits as sexually selected individual quality indices by revealing a well-adjusted oxidative metabolism. We administered mitochondria-targeted molecules to male zebra finches ( Taeniopygia guttata ) measuring their bill redness, a trait produced by transforming yellow carotenoids. One molecule included coQ 10 (mitoquinone mesylate, MitoQ) and the other one (decyl-triphenylphosphonium; dTPP) has the same structure without the coQ 10 aromatic ring. At the highest dose, the bill colour of MitoQ and dTPP birds strongly differed: MitoQ birds' bills were redder and dTPP birds showed paler bills even compared to birds injected with saline only. These results suggest that ketolases are indeed placed at the IMM and that coQ 10 antioxidant properties may improve their efficiency. The implications for evolutionary theories of sexual signalling are discussed. © 2017 The Author(s).

Early steps in steroidogenesis: intracellular cholesterol trafficking

PubMed Central

Miller, Walter L.; Bose, Himangshu S.

2011-01-01

Steroid hormones are made from cholesterol, primarily derived from lipoproteins that enter cells via receptor-mediated endocytosis. In endo-lysosomes, cholesterol is released from cholesterol esters by lysosomal acid lipase (LAL; disordered in Wolman disease) and exported via Niemann-Pick type C (NPC) proteins (disordered in NPC disease). These diseases are characterized by accumulated cholesterol and cholesterol esters in most cell types. Mechanisms for trans-cytoplasmic cholesterol transport, membrane insertion, and retrieval from membranes are less clear. Cholesterol esters and “free” cholesterol are enzymatically interconverted in lipid droplets. Cholesterol transport to the cholesterol-poor outer mitochondrial membrane (OMM) appears to involve cholesterol transport proteins. Cytochrome P450scc (CYP11A1) then initiates steroidogenesis by converting cholesterol to pregnenolone on the inner mitochondrial membrane (IMM). Acute steroidogenic responses are regulated by cholesterol delivery from OMM to IMM, triggered by the steroidogenic acute regulatory protein (StAR). Chronic steroidogenic capacity is determined by CYP11A1 gene transcription. StAR mutations cause congenital lipoid adrenal hyperplasia, with absent steroidogenesis, potentially lethal salt loss, and 46,XY sex reversal. StAR mutations initially destroy most, but not all steroidogenesis; low levels of StAR-independent steroidogenesis are lost later due to cellular damage, explaining the clinical findings. Rare P450scc mutations cause a similar syndrome. This review addresses these early steps in steroid biosynthesis. PMID:21976778

Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).

PubMed

Pont, Laura; Benavente, Fernando; Vilaseca, Marta; Giménez, Estela; Sanz-Nebot, Victoria

2015-11-01

Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I. Copyright © 2015 Elsevier B.V. All rights reserved.

Medical Optimization Network for Space Telemedicine Resources

NASA Technical Reports Server (NTRS)

Rubin, D.; Shah, R. V.; Kerstman, E. L.; Reyes, D.; Mulcahy, R.; Antonsen, E.

2017-01-01

INTRODUCTION: Long-duration missions beyond low Earth orbit introduce new constraints to the space medical system. Beyond the traditional limitations in mass, power, and volume, consideration must be given to other factors such as the inability to evacuate to Earth, communication delays, and limitations in clinical skillsets. As NASA develops the medical system for an exploration mission, it must have an ability to evaluate the trade space of what resources will be most important. The Medical Optimization Network for Space Telemedicine Resources (MONSTR) was developed over the past year for this reason, and is now a system for managing data pertaining to medical resources and their relative importance when addressing medical conditions. METHODS: The MONSTR web application with a Microsoft SQL database backend was developed and made accessible to Tableau v9.3 for analysis and visualization. The database was initially populated with a list of medical conditions of concern for an exploration mission taken from the Integrated Medical Model (IMM), a probabilistic model designed to quantify in-flight medical risk. A team of physicians working within the Exploration Medical Capability Element of NASA's Human Research Program compiled a list diagnostic and treatment medical resources required to address best- and worst-case scenarios of each medical condition using a terrestrial standard of care and entered this data into the system. This list included both tangible resources (e.g. medical equipment, medications) and intangible resources (e.g. clinical skills required to perform a procedure). The physician team then assigned criticality values to each instance of a resource, representing the importance of that resource to diagnosing or treating its associated condition(s). Medical condition probabilities of occurrence during a Mars mission were pulled from the IMM and imported into the MONSTR database for use within a resource criticality-weighting algorithm. DISCUSSION: The MONSTR tool is a novel approach to assess the relative value of individual resources needed for the diagnosis and treatment of medical conditions. Future work will add resources for prevention and long term care of these conditions. Once data collection is complete, MONSTR will provide the operational and research communities at NASA with information to support informed decisions regarding areas of research investment, future crew training, and medical supplies manifested as part of any exploration medical system.

Mobile Laser Scanning for Indoor Modelling

NASA Astrophysics Data System (ADS)

Thomson, C.; Apostolopoulos, G.; Backes, D.; Boehm, J.

2013-10-01

The process of capturing and modelling buildings has gained increased focus in recent years with the rise of Building Information Modelling (BIM). At the heart of BIM is a process change for the construction and facilities management industries whereby a BIM aids more collaborative working through better information exchange, and as a part of the process Geomatic/Land Surveyors are not immune from the changes. Terrestrial laser scanning has been proscribed as the preferred method for rapidly capturing buildings for BIM geometry. This is a process change from a traditional measured building survey just with a total station and is aided by the increasing acceptance of point cloud data being integrated with parametric building models in BIM tools such as Autodesk Revit or Bentley Architecture. Pilot projects carried out previously by the authors to investigate the geometry capture and modelling of BIM confirmed the view of others that the process of data capture with static laser scan setups is slow and very involved requiring at least two people for efficiency. Indoor Mobile Mapping Systems (IMMS) present a possible solution to these issues especially in time saved. Therefore this paper investigates their application as a capture device for BIM geometry creation over traditional static methods through a fit-for-purpose test.

Reflectance of micron-sized dust particles retrieved with the Umov law

NASA Astrophysics Data System (ADS)

Zubko, Evgenij; Videen, Gorden; Zubko, Nataliya; Shkuratov, Yuriy

2017-03-01

The maximum positive polarization Pmax that initially unpolarized light acquires when scattered from a particulate surface inversely correlates with its geometric albedo A. In the literature, this phenomenon is known as the Umov law. We investigate the Umov law in application to single-scattering submicron and micron-sized agglomerated debris particles, model particles that have highly irregular morphology. We find that if the complex refractive index m is constrained to Re(m)=1.4-1.7 and Im(m)=0-0.15, model particles of a given size distribution have a linear inverse correlation between log(Pmax) and log(A). This correlation resembles what is measured in particulate surfaces, suggesting a similar mechanism governing the Umov law in both systems. We parameterize the dependence of log(A) on log(Pmax) of single-scattering particles and analyze the airborne polarimetric measurements of atmospheric aerosols reported by Dolgos & Martins in [1]. We conclude that Pmax ≈ 50% measured by Dolgos & Martins corresponds to very dark aerosols having geometric albedo A=0.019 ± 0.005.

Nonspecific Resistance Induced by an Immunopharmacologic Agent Derived from Bordetella pertussis.

DTIC Science & Technology

1985-01-31

NONSPECIFIC RESISTANCE INDUCED BY AN IMM1JNOPHAL’-ACOLOGIC AGENT DERIVED FROM a u’seeOG EoTwwE BORDE2’ELLA PERTUSSIS * OTATO RN UU~e AU THOR(*) B OTATO RN...antibodies 20. A 9STRPACT (Con tnue an revwre side It necessary and fdontitlP Ip 5149k IeebffJ LJ..JTreatment of mice with Bordetella pertueeis vaccine...resulted in * resistance to mouse adenovirus infection. Antiviral activity was associated with surface components of B. pertussie . Acellular fractions with

Survey of Evaluated Isobaric Analog States

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

MacCormick, M., E-mail: maccorm@ipno.in2p3.fr; Audi, G.

Isobaric analog states (IAS) can be used to estimate the masses of members belonging to the same isospin multiplet. Experimental and estimated IAS have been used frequently within the Atomic Mass Evaluation (AME) in the past, but the associated set of evaluated masses have been published for the first time in AME2012 and NUBASE2012. In this paper the current trends of the isobaric multiplet mass equation (IMME) coefficients are shown. The T = 2 multiplet is used as a detailed illustration.

Development of Spontaneous Mammary Tumors in BALB/c-p53+/-Mice: Detection of Early Genetic Alterations and the Mapping of BALB/c Susceptibility Genes

DTIC Science & Technology

2005-07-01

type allele in the sample, with one being a papillary ductal study used all BALB/c female mice; therefore, both strain and gender hyperplasia and the...other being a solid adenocarcinoma but with a could be contributing to the difference in LOH frequency. To deter- significant fibrous stromal...Intracytoplasmic granular staining in the epithelium was the most common pattern of staining and was regarded as positive. Imm unoreactivity in inflammatory

ALOFT Flight Test Report

DTIC Science & Technology

1977-10-01

China Lake, CA 93555. USNWC ltr, 1Mar 1978 THIS REPORT HAS BEEN DELIMITED AND CLEARED FOR PUBLIC RELEASE UNDER DOD DIRECTIVE 5200,20 AND NO...wmmmmmmmmmmmm i ifmu.immM\\]i\\ ßinimm^mmmmviwmmiwui »vimtm twfjmmmmmmi c-f—rmSmn NWC TP 5954 ALOFT Flight Test Report by James D. Ross anrJ I.. M...results of tests on a fiber optic data link, manufactured by International Business Machines (IBM) under Contract No. N0O«3J6^򒹁 for the Naval

Soviet Frontal Aviation Operations: Concepts and Problems,

DTIC Science & Technology

1981-06-01

recent exercises. For example, during Operation " Neman " (23-27 July " ’ 1979 in the Baltic MD) a fighter/bomber squadron was assigned the mission of...area. For example, during Operation " Neman ", the commander of a helicopter strike force "did not succeed in imme lately orienting himself on the terrain...Kosmonavtika, #11, 1980) comparison of two different (one correct, one incorrect) techniques used in such operations during Exercise " Neman ". 2 6"Voyska PVO na

Regulation of 2-5A Dependent RNase at the Level of its Phosphorylation

DTIC Science & Technology

1991-06-26

extract as follows: 25 ul wheat germ extract 10 ul H2O 1 ul RNasin ribonuclease inhibitor (40 u/ml) 7 ul ImM amino acid mixture 1 ul IM...diacylglycerol (DAG) 2. TPA 3. Indolactam Figure 6. Chemical structure of: 1. H-7 (A kinase inhibitor) 2. okadaic acid (A phosphatase inhibitor) Figure 7...elevating agents: Forskolin and Cholera toxin Figure 17. Down-regulation of 2-5A-depRNase by Okadaic 77 acid : A phosphatase inhibitor Figure 18

Determination of cloxacillin residues in dairy cows after intramammary administration.

PubMed

Burmańczuk, A; Grabowski, T; Osypiuk, M; Polska, B; Kowalski, C

2017-10-01

The aim of this study was to perform a comparative analysis of the characteristics of cloxacillin (CLO) (MRL of withdrawal in bovine milk is 30 ng/g) after a single intramammary (IMM) dose in the dry period (DP) and lactation (LP), and to establish a high-performance liquid chromatography (HPLC) analytical method for CLO detection in milk. The research was conducted on a group of 10 cows in DP and 10 in LP. A single dose of 600 mg of CLO was administrated by the IMM route for a single quarter in DP and 500 mg for a single quarter in LP. CLO concentration was analyzed by HPLC. CLO was monitored at a wavelength of 206 nm. Pharmacokinetic calculations were performed using Phoenix ® WinNonlin ® 6.4 software. The calibration curve was linear over the range of 13.03-28 019.00 ng/g with the coefficient of determination R 2  > 0.999. CLO withdrawal in both the LP and DP group had a biphasic nature. The total CLO elimination in the DP and LP group was reached after 36 and 6.5 days, respectively. A quantitative and confirmatory method for the determination of CLO in fresh milk has been established. We have confirmed that the withdrawal of CLO in the DP group is not a linear process and has a stepwise character. © 2017 John Wiley & Sons Ltd.

Measurement of Mitochondrial Cholesterol Import Using a Mitochondria-Targeted CYP11A1 Fusion Construct.

PubMed

Kennedy, Barry E; Charman, Mark; Karten, Barbara

2017-01-01

All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease. The mechanisms of mitochondrial cholesterol import are not fully elucidated yet, and may vary in different cell types and environmental conditions. Measuring cholesterol trafficking to the mitochondrial membranes is technically challenging because of its low abundance; for example, traditional pulse-chase experiments with isotope-labeled cholesterol are not feasible. Here, we describe improvements to a method first developed by the Miller group at the University of California to measure cholesterol trafficking to the inner mitochondrial membrane (IMM) through the conversion of cholesterol to pregnenolone. This method uses a mitochondria-targeted, ectopically expressed fusion construct of CYP11A1, ferredoxin reductase and ferredoxin. Pregnenolone is formed exclusively from cholesterol at the IMM, and can be analyzed with high sensitivity and specificity through ELISA or radioimmunoassay of the medium/buffer to reflect mitochondrial cholesterol import. This assay can be used to investigate the effects of genetic or pharmacological interventions on mitochondrial cholesterol import in cultured cells or isolated mitochondria.

Interactive Machine Learning at Scale with CHISSL

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

Arendt, Dustin L.; Grace, Emily A.; Volkova, Svitlana

We demonstrate CHISSL, a scalable client-server system for real-time interactive machine learning. Our system is capa- ble of incorporating user feedback incrementally and imme- diately without a structured or pre-defined prediction task. Computation is partitioned between a lightweight web-client and a heavyweight server. The server relies on representation learning and agglomerative clustering to learn a dendrogram, a hierarchical approximation of a representation space. The client uses only this dendrogram to incorporate user feedback into the model via transduction. Distances and predictions for each unlabeled instance are updated incrementally and deter- ministically, with O(n) space and time complexity. Our al- gorithmmore » is implemented in a functional prototype, designed to be easy to use by non-experts. The prototype organizes the large amounts of data into recommendations. This allows the user to interact with actual instances by dragging and drop- ping to provide feedback in an intuitive manner. We applied CHISSL to several domains including cyber, social media, and geo-temporal analysis.« less

Boundary Layer Structure and Its Relation to Precipitation Over the St. Louis Area.

DTIC Science & Technology

1980-10-01

of METEORO LOGY SECTION 0i{1J ( 0I~) AT THE mp UNI VERSITY OV ILLINOIS0 SMISContract Report 241 T - BOUNDARY LAYER STRUCTURE AND ITS RELATION TO...PRECIPITATION OVER THE ST. LOUIS AREA Gary L. Achtemeier Meteorology Section Ill1inois State Water &uIvey, DTII CLeELEC T E C.> JAN 15 1981( Technical...in f r ’TNil PA&F rlhImm Does Rnteredl 𔄃. -. , .’.-..,. -.- -/" . ECumITYv CLASSFICATIOW Of TH t PAGE(Wfhn Date Entr,.e) 15529. 4-GS ?0. ABSTRACT

Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms.

PubMed

El Hajji, Feras W D; Scullin, Claire; Scott, Michael G; McElnay, James C

2015-04-01

This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized. © 2014 John Wiley & Sons, Ltd.

Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.

PubMed

Gastón, M S; Cid, M P; Salvatierra, N A

2017-03-01

Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABA A receptor competitive antagonist) but not by diazepam (a GABA A receptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is still unclear whether this effect of ghrelin is associated with HPA activation. Therefore, we investigated whether anxiety behavior induced by intra-IMM ghrelin and mediated through GABA A receptors could be associated with HPA axis activation in the neonatal chick. In the present study, in an Open Field test, intraperitoneal bicuculline methiodide blocked anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30pmol) in neonatal chicks. Moreover, we showed for the first time that a competitive antagonist of GABA A receptor suppressed the HPA axis activation induced by an anxiogenic dose of ghrelin. These results show that the anxiogenic ghrelin action involves the activation of the HPA axis, with a complex functional interaction with the GABA A receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

Editorial overview: Omics

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

Barran, Perdita; Baker, Erin

The great complexity of biological systems and their environment poses similarly vast challenges for accurate analytical evaluations of their identity, structure and quantity. Post genomic science, has predicted much regarding the static populations of biological systems, but a further challenge for analysis is to test the accuracy of these predictions, as well as provide a better representation of the transient nature of the molecules of life. Accurate measurements of biological systems have wide applications for biological, forensic, biotechnological and healthcare fields. Therefore, the holy grail is to find a technique which can identify and quantify biological molecules with high throughput,more » sensitivity and robustness, as well evaluate molecular structure(s) in order to understand how the specific molecules interact and function. While wrapping all of these characteristics into one platform may sound difficult, ion mobility spectrometry (IMS) is addressing all of these challenges. Over the last decade, the number of analytical studies utilizing IMS for the evaluation of complex biological and environmental samples has greatly increased. In most cases IMS is coupled with mass spectrometry (IM-MS), but even alone IMS provides the unique capability of rapidly assessing a molecule’s structure, which can be extremely difficult with other techniques. The robustness of the IMS measurement is bourne out by its widespread use in security, environmental and military applications. The multidimensional IM-MS measurements however have been proven to be ever more powerful, as applied to complex mixtures as they enable the evaluation of both the structure and mass of every molecular component in a sample during a single measurement, without the need for continual reference calibration.« less

Can We Trust Computational Modeling for Medical Applications?

NASA Technical Reports Server (NTRS)

Mulugeta, Lealem; Walton, Marlei; Nelson, Emily; Myers, Jerry

2015-01-01

Operations in extreme environments such as spaceflight pose human health risks that are currently not well understood and potentially unanticipated. In addition, there are limited clinical and research data to inform development and implementation of therapeutics for these unique health risks. In this light, NASA's Human Research Program (HRP) is leveraging biomedical computational models and simulations (M&S) to help inform, predict, assess and mitigate spaceflight health and performance risks, and enhance countermeasure development. To ensure that these M&S can be applied with confidence to the space environment, it is imperative to incorporate a rigorous verification, validation and credibility assessment (VV&C) processes to ensure that the computational tools are sufficiently reliable to answer questions within their intended use domain. In this presentation, we will discuss how NASA's Integrated Medical Model (IMM) and Digital Astronaut Project (DAP) have successfully adapted NASA's Standard for Models and Simulations, NASA-STD-7009 (7009) to achieve this goal. These VV&C methods are also being leveraged by organization such as the Food and Drug Administration (FDA), National Institute of Health (NIH) and the American Society of Mechanical Engineers (ASME) to establish new M&S VV&C standards and guidelines for healthcare applications. Similarly, we hope to provide some insight to the greater aerospace medicine community on how to develop and implement M&S with sufficient confidence to augment medical research and operations.

Engine Fluid Leakage Detection: A Feasibility Study

DTIC Science & Technology

2011-07-01

2011 © Sa Majesté la Reine (en droit du Canada), telle que représentée par le ministre de la Défense nationale, 2011 DRDC Atlantic TM 2011-050 i... de détecter tout problème possible lié à la sécurité ou aux performances des moteurs à turbine à gaz d’aéronefs. Le signalement immédiat d’une fuite...carburant ou d’huile moteur nuisent non seulement aux performances d’un moteur, mais elles représentent également une menace réelle pour la sécurité de

Strategy Toward the Total Synthesis of Epothilones A and B

DTIC Science & Technology

1999-07-01

2-(iV-morpholino)ethanesulfonic acid ). 1 mM EGTA(1.2-di(2-aminoethoxy)ethane-/V..V..V’.Af’-tetraaceticacid). 0.5 mM MgCl2, 1 mM GTP. and 3 M... acid ), 1 mM EGTA. 0.5 nM MgCU. ImM GTP and 3M glyceropH £6- Tta concentration of tubulin in MTP was estimated to be about 85%. Assembly was...fragment projected for the olefin metathesis step. For this purpose, it would be appropriate to reach a carboxylic acid (cf. 28, Scheme 4) for

Using Nonequilibrium Alloying Techniques for Corrosion Inhibition in Gr/ Al and Gr/Mg Metal Matrix Composites

DTIC Science & Technology

1994-06-15

of AI-12Mg-13Sf Before and After Heat Treament at 400C for 1, 2 and 8 hre and 5000C for I hr, Polarized in Quiescent 0. IM NaCI, pH 8, 2W°C. 8 0.8 AI...C4 4R o00qI i co c cc o !00§ " 00- 0-coo 88 88-- o IMM CCO 00 PP0M 3I34 -1.2 M9 - TreaMent #1 .1.4 ~ 1.5 .7 -6 -5 -4 -3 -2 - Current Denedty, log (A

Lambeaux autofermants pour le traitement des brulures electriques du scalp par haut voltage

PubMed Central

Hafidi, J.; El Mazouz, S.; El Mejatti, H.; Fejjal, N.; Gharib, N.E.; Abbassi, A.; Belmahi, A.M.

2011-01-01

Summary Les brûlures électriques par haut voltage sont responsables de gros dégâts tissulaires en immédiat et dans les jours suivant l’accident du fait de la chaleur importante dégagée par effet joule et de la thrombose microvasculaire évolutive. Les pertes de substances du scalp secondaires à ces brûlures nécessitent une couverture par lambeaux vu la destruction du périoste et du calvarium en regard. De juin 1997 à juin 2008, 15 patients ont été traités pour des pertes de substance du scalp secondaires à des brûlures électriques par haut voltage de diamètre allant de 8 à 11 cm et siégeant dans la région tonsurale. Ces patients ont été opérés dans la première semaine suivant l’accident. Les pertes de substance du scalp de taille moyenne secondaires à ces brûlures peuvent être couvertes per primam de façon fiable par des lambeaux locaux axialisés et multiples. Nous relatons l’expérience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc, dans la gestion et la prise en charge de ces brûlures. PMID:22262963

Cryopreservation of lipid bilayers by LEA proteins from Artemia franciscana and trehalose.

PubMed

Moore, Daniel S; Hand, Steven C

2016-10-01

The capacity of Late Embryogenesis Abundant (LEA) proteins and trehalose to protect liposomes against freezing-induced damage was examined by measuring the leakage of 5(6)-carboxyfluorescein (CF). Liposomes were prepared to simulate the lipid compositions of the inner leaflet of the plasma membrane, outer mitochondrial membrane (OMM), and inner mitochondrial membrane (IMM). Two recombinant LEA proteins belonging to Group 3 (AfrLEA2 and AfrLEA3m) were expressed and purified from embryos of Artemia franciscana. Only OMM-like liposomes were significantly protected by AfrLEA2 and AfrLEA3m against freeze-thaw damage; at the highest protein:lipid mass ratio tested, leakage of CF was 56.3% of control with AfrLEA3m and 29.3% with AfrLEA2. By comparison, trehalose provided protection to all compositional types. The greatest stabilization during freezing occurred when trehalose was present on both sides of the bilayer. When mitochondria isolated from rat liver were freeze-thawed in trehalose solution, the OMM remained intact based on the absence of increased oxygen consumption when cytochrome c was added during oxidative phosphorylation (OXPHOS). Respiratory control ratios (OXPHOS/LEAK) were depressed by only 30% after freeze-thawing in trehalose compared to non-frozen controls, which indicated some retention of OXPHOS capacity by the IMM. Trehalose then was loaded into the matrix (0.24 μmol/mg mitochondrial protein) by transient opening of the permeability transition pore, a procedure optimized for retention of OMM integrity. Surprisingly, respiratory control ratios were not improved after freeze-thawing with external plus matrix trehalose, when compared to external trehalose alone. This result could perhaps be explained by insufficient accumulation of matrix trehalose. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

PubMed Central

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-01-01

Background/Aims To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Methods Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. Results This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). Conclusions ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA. PMID:26780088

Dissecting the dynamic conformations of the metamorphic protein lymphotactin.

PubMed

Harvey, Sophie R; Porrini, Massimiliano; Konijnenberg, Albert; Clarke, David J; Tyler, Robert C; Langridge-Smith, Patrick R R; MacPhee, Cait E; Volkman, Brian F; Barran, Perdita E

2014-10-30

A mass spectrometer provides an ideal laboratory to probe the structure and stability of isolated protein ions. Interrogation of each discrete mass/charge-separated species enables the determination of the intrinsic stability of a protein fold, gaining snapshots of unfolding pathways. In solution, the metamorphic protein lymphotactin (Ltn) exists in equilibrium between two distinct conformations, a monomeric (Ltn10) and a dimeric (Ltn40) fold. Here, we use electron capture dissociation (ECD) and drift tube ion mobility-mass spectrometry (DT IM-MS) to analyze both forms and use molecular dynamics (MD) to consider how the solution fold alters in a solvent-free environment. DT IM-MS reveals significant conformational flexibility for the monomer, while the dimer appears more conformationally restricted. These findings are supported by MD calculations, which reveal how salt bridges stabilize the conformers in vacuo. Following ECD experiments, a distinctive fragmentation pattern is obtained for both the monomer and dimer. Monomer fragmentation becomes more pronounced with increasing charge state especially in the disordered regions and C-terminal α-helix in the solution fold. Lower levels of fragmentation are seen in the β-sheet regions and in regions that contain salt bridges, identified by MD simulations. The lowest charge state of the dimer for which we obtain ECD data ([D+9H](9+)) exhibits extensive fragmentation with no relationship to the solution fold and has a smaller collision cross section (CCS) than charge states 10-13+, suggesting a "collapsed" encounter complex. Other charge states of the dimer, as for the monomer, are resistant to fragmentation in regions of β-sheets in the solution fold. This study provides evidence for preservation and loss of global fold and secondary structural elements, providing a tantalizing glimpse into the power of the emerging field of native top-down mass spectrometry.

Mitochondrial aquaporin-8 in renal proximal tubule cells: evidence for a role in the response to metabolic acidosis.

PubMed

Molinas, Sara M; Trumper, Laura; Marinelli, Raúl A

2012-08-01

Mitochondrial ammonia synthesis in proximal tubules and its urinary excretion are key components of the renal response to maintain acid-base balance during metabolic acidosis. Since aquaporin-8 (AQP8) facilitates transport of ammonia and is localized in inner mitochondrial membrane (IMM) of renal proximal cells, we hypothesized that AQP8-facilitated mitochondrial ammonia transport in these cells plays a role in the response to acidosis. We evaluated whether mitochondrial AQP8 (mtAQP8) knockdown by RNA interference is able to impair ammonia excretion in the human renal proximal tubule cell line, HK-2. By RT-PCR and immunoblotting, we found that AQP8 is expressed in these cells and is localized in IMM. HK-2 cells were transfected with short-interfering RNA targeting human AQP8. After 48 h, the levels of mtAQP8 protein decreased by 53% (P < 0.05). mtAQP8 knockdown decreased the rate of ammonia released into culture medium in cells grown at pH 7.4 (-31%, P < 0.05) as well as in cells exposed to acid (-90%, P < 0.05). We also evaluated mtAQP8 protein expression in HK-2 cells exposed to acidic medium. After 48 h, upregulation of mtAQP8 (+74%, P < 0.05) was observed, together with higher ammonia excretion rate (+73%, P < 0.05). In vivo studies in NH(4)Cl-loaded rats showed that mtAQP8 protein expression was also upregulated after 7 days of acidosis in renal cortex (+51%, P < 0.05). These data suggest that mtAQP8 plays an important role in the adaptive response of proximal tubule to acidosis possibly facilitating mitochondrial ammonia transport.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

PubMed

Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

2015-04-01

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: Potential relevance of limbic GAD

PubMed Central

Ortiz, J. Bryce; Taylor, Sara B.; Hoffman, Ann N.; Campbell, Alyssa N.; Lucas, Louis R.; Conrad, Cheryl D.

2015-01-01

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for two days and given one retention trial on the third day, with brains removed 30 minutes later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. PMID:25591480

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials.

PubMed

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-03-01

To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.

Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

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

Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. Here, we demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing Al xGayIn 1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted Ga xIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted Ga xIn 1-xP on B-miscut substrates and Al xGayIn 1-x-yAs/Ga xIn 1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibitmore » Woc = 0.41 V at mA/ cm 2, performance comparable with the state-of-the-art Ga xIn 1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted Ga xIn 1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. Furthermore, this tandem represents a highly efficient two-junction band gap combination, achieving 29.6% ± 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.« less

Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

DOE PAGES

Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

2016-11-11

The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. Here, we demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing Al xGayIn 1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted Ga xIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted Ga xIn 1-xP on B-miscut substrates and Al xGayIn 1-x-yAs/Ga xIn 1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibitmore » Woc = 0.41 V at mA/ cm 2, performance comparable with the state-of-the-art Ga xIn 1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted Ga xIn 1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. Furthermore, this tandem represents a highly efficient two-junction band gap combination, achieving 29.6% ± 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.« less

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

PubMed

Valk, B I; Absalom, A R; Meyer, P; Meier, S; den Daas, I; van Amsterdam, K; Campagna, J A; Sweeney, S P; Struys, M M R F

2018-06-01

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg -1  min -1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. NTR4735. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Signatures of Mechanically Interlocked Topology of Lasso Peptides by Ion Mobility-Mass Spectrometry: Lessons from a Collection of Representatives

NASA Astrophysics Data System (ADS)

Fouque, Kevin Jeanne Dit; Lavanant, Hélène; Zirah, Séverine; Hegemann, Julian D.; Zimmermann, Marcel; Marahiel, Mohamed A.; Rebuffat, Sylvie; Afonso, Carlos

2017-02-01

Lasso peptides are characterized by a mechanically interlocked structure, where the C-terminal tail of the peptide is threaded and trapped within an N-terminal macrolactam ring. Their compact and stable structures have a significant impact on their biological and physical properties and make them highly interesting for drug development. Ion mobility - mass spectrometry (IM-MS) has shown to be effective to discriminate the lasso topology from their corresponding branched-cyclic topoisomers in which the C-terminal tail is unthreaded. In fact, previous comparison of the IM-MS data of the two topologies has yielded three trends that allow differentiation of the lasso fold from the branched-cyclic structure: (1) the low abundance of highly charged ions, (2) the low change in collision cross sections (CCS) with increasing charge state and (3) a narrow ion mobility peak width. In this study, a three-dimensional plot was generated using three indicators based on these three trends: (1) mean charge divided by mass (ζ), (2) relative range of CCS covered by all protonated molecules (ΔΩ/Ω) and (3) mean ion mobility peak width (δΩ). The data were first collected on a set of twenty one lasso peptides and eight branched-cyclic peptides. The indicators were obtained also for eight variants of the well-known lasso peptide MccJ25 obtained by site-directed mutagenesis and further extended to five linear peptides, two macrocyclic peptides and one disulfide constrained peptide. In all cases, a clear clustering was observed between constrained and unconstrained structures, thus providing a new strategy to discriminate mechanically interlocked topologies.

The NASA Human Research Wiki - An Online Collaboration Tool

NASA Technical Reports Server (NTRS)

Barr, Yael; Rasbury, Jack; Johnson, Jordan; Barstend, Kristina; Saile, Lynn; Watkins, Sharmi

2012-01-01

The Exploration Medical Capability (ExMC) element is one of six elements of the Human Research Program (HRP). ExMC is charged with decreasing the risk of: "Inability to adequately recognize or treat an ill or injured crew member" for exploration-class missions In preparation for exploration-class missions, ExMC has compiled a large evidence base, previously available only to persons within the NASA community. ExMC has developed the "NASA Human Research Wiki" in an effort to make the ExMC information available to the general public and increase collaboration within and outside of NASA. The ExMC evidence base is comprised of several types of data, including: (1)Information on more than 80 medical conditions which could occur during space flight (a)Derived from several sources (b)Including data on incidence and potential outcomes, as captured in the Integrated Medical Model s (IMM) Clinical Finding Forms (CliFFs). (2)Approximately 25 gap reports (a)Identify any "gaps" in knowledge and/or technology that would need to be addressed in order to provide adequate medical support for these novel missions.

Recent Space PV Concentrator Advances: More Robust, Lighter, and Easier to Track

NASA Technical Reports Server (NTRS)

O'Neill, Mark; McDanal, A. J.; Brandhorst, Henry; Schmid, Kevin; LaCorte, Peter; Piszczor, Michael; Myers, Matt

2015-01-01

Over the past three years, the authors have collaborated on several significant advances in space photovoltaic concentrator technology, including a far more robust Fresnel lens for sunlight concentration, improved color-mixing features for the lens to minimize chromatic aberration losses for next-generation 4-junction and 6-junction IMM cells, a new approach to suntracking requiring only one axis of rotation even in the presence of large beta angles (e.g., +/- 50 deg), a new waste heat radiator made of graphene, with 80-90% reduction in mass, and a new platform for deployment and support on orbit (SOLAROSA). These patent-pending advances are described in this paper.

Digital immunization registry: evidence for the impact of mHealth on enhancing the immunization system and improving immunization coverage for children under one year old in Vietnam.

PubMed

Nguyen, Nga Tuyet; Vu, Huong Minh; Dao, Sang Dinh; Tran, Hieu Trung; Nguyen, Tu Xuan Cam

2017-01-01

The Vietnam National Expanded Program on Immunization (NEPI) has been successfully implementing a nationwide immunization system since 1985. From the start, the program has increased the immunization coverage rate; however, data on immunization coverage in Vietnam are gathered and aggregated from commune health centers in routine, paper-based reports, which have shortcomings. Also, calculations of coverage are inconsistent at subnational levels, which lead to uncertainty about the size of the target population used as the denominator in coverage calculations. The growth of mobile networks in Vietnam provides an opportunity to apply mHealth to improve the immunization program. In 2012, PATH and the Vietnam NEPI developed and piloted a digital immunization registry, ImmReg, to overcome the challenges of the paper system. A final evaluation was conducted in 2015 to assess the impact of ImmReg, including its use of SMS reminders, on improving the immunization program. The study population comprised all children born in Ben Tre province in September and October of 2013, 2014, and 2015, representing pre-intervention, post-intervention, and one year post-intervention, respectively. Data exported from ImmReg were used to compare the immunization rate, dropout rate, and timeliness of vaccination before and after the intervention. Additionally, a rapid survey was conducted to understand the willingness of parents with children due for vaccination to pay for SMS reminder messages on the immunization schedule. Timely administration of oral polio vaccine, Quinvaxem, and measles 1 vaccine significantly increased over time from baseline to post-intervention to one year post-intervention. In particular, the timeliness of vaccination with the third dose of Quinvaxem increased from 53.6% to 65.8% to 77.2%. For measles 1 vaccine, the rate increased from 70.4% to 76.2% to 92.3%. In addition, the dropout rate from Quinvaxem 1 to Quinvaxem 3 declined from 4.2% in 2013 to 0% in 2015, and the dropout rate from Bacillus Calmette-Guérin (BCG) to measles 1 fell from 12.8% in 2013 to 0% in 2015. Full immunization coverage of children under one year old increased significantly from 75.4% in 2013 to 81.7% in 2014 to 99.2% in 2015. Also, survey results indicated that 93.3% of interviewees were willing to pay for SMS reminders for immunization. A digital immunization registry that includes SMS reminders can improve immunization coverage and timeliness of vaccination, thereby strengthening the quality and effectiveness of immunization programs. Integrating this system into the national health information system and leveraging it for other health programs, such as maternal and child health and nutrition as well as infectious disease control, can bring more benefits to the health care system in Vietnam.

Elucidation of Seventeen Human Peripheral Blood B cell Subsets and Quantification of the Tetanus Response Using a Density-Based Method for the Automated Identification of Cell Populations in Multidimensional Flow Cytometry Data

PubMed Central

Qian, Yu; Wei, Chungwen; Lee, F. Eun-Hyung; Campbell, John; Halliley, Jessica; Lee, Jamie A.; Cai, Jennifer; Kong, Megan; Sadat, Eva; Thomson, Elizabeth; Dunn, Patrick; Seegmiller, Adam C.; Karandikar, Nitin J.; Tipton, Chris; Mosmann, Tim; Sanz, Iñaki; Scheuermann, Richard H.

2011-01-01

Background Advances in multi-parameter flow cytometry (FCM) now allow for the independent detection of larger numbers of fluorochromes on individual cells, generating data with increasingly higher dimensionality. The increased complexity of these data has made it difficult to identify cell populations from high-dimensional FCM data using traditional manual gating strategies based on single-color or two-color displays. Methods To address this challenge, we developed a novel program, FLOCK (FLOw Clustering without K), that uses a density-based clustering approach to algorithmically identify biologically relevant cell populations from multiple samples in an unbiased fashion, thereby eliminating operator-dependent variability. Results FLOCK was used to objectively identify seventeen distinct B cell subsets in a human peripheral blood sample and to identify and quantify novel plasmablast subsets responding transiently to tetanus and other vaccinations in peripheral blood. FLOCK has been implemented in the publically available Immunology Database and Analysis Portal – ImmPort (http://www.immport.org) for open use by the immunology research community. Conclusions FLOCK is able to identify cell subsets in experiments that use multi-parameter flow cytometry through an objective, automated computational approach. The use of algorithms like FLOCK for FCM data analysis obviates the need for subjective and labor intensive manual gating to identify and quantify cell subsets. Novel populations identified by these computational approaches can serve as hypotheses for further experimental study. PMID:20839340

AMPK activation enhances the anti-atherogenic effects of high density lipoproteins in apoE-/- mice.

PubMed

Ma, Ang; Wang, Jing; Yang, Liu; An, Yuanyuan; Zhu, Haibo

2017-08-01

HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE -/- ) mice fed with a high-fat diet. After administration, there were no changes in serum lipid levels among the groups. However, mice treated with AMPK activators showed significantly enhanced reverse cholesterol transport in vivo and in vitro. AMPK activation also increased the expression of ABCA1 and ABCG1 in macrophages and scavenger receptor class B type I and LCAT in the liver. HDL from AMPK activation mice exhibited lower HDL inflammatory index and myeloperoxidase activity and higher paraoxonase 1 activity than HDL from untreated mice, implying superior antioxidant and anti-inflammatory capacities. Pharmacological AMPK activation also induced polarization of macrophages to the M2 state and reduced plasma lipid peroxidation, inflammatory cytokine production, and atherosclerotic plaque formation in apoE -/- mice. These observations suggest that pharmacological AMPK activation enhances the anti-atherogenic properties of HDL in vivo. This likely represents a key mechanism by which AMPK activation attenuates atherosclerosis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Low-energy laser biostimulation therapy of musculoskeletal disorders: clinical study

NASA Astrophysics Data System (ADS)

Filonenko, Natalia; Livshitz, Oleg; Salansky, Norman M.

1992-06-01

215 patients (86 males and 129 females, average age 60.3 years) suffering from musculoskeletal and neuromuscular disorders, both chronic and acute, were treated by low energy lasers. Most patients failed to improve in spite of the fact that different conventional treatment modalities were implemented. Some of them were unable to tolerate drugs because of allergy or gastrointestinal intolerance. The photobiostimulation system FABULIGHTTM (IMM Inc., Canada) with adjustable output parameters for both red and infrared wavelength was used. Different modalities of LELBT were used: local and generalized stimulation of tender points and affected areas. Stiffness, swelling, range of motion and pain were assessed. 65% of symptoms improvement was obtained in average.

A System Dynamics Based Study of Software Reuse Economics

DTIC Science & Technology

1994-06-01

USE ONLY tLeavo biak) 12 WEORT DATE 3 REPORT TYPE AND DATES COVERED ~1994 Mamaer’s Them, Final TIrLE AND WITMTL 5 FLNDN~G NUMBERS A Syvm Dyanows bwed...ppoms WON moved by Ovnm ad Ono dp af is$ m rows I% 6imm A be .mmec immm some wa arna #fu copo uo.* *a Owm. Un lmad. Ww medo a*iio a w o - --- d a...wo-4wm OmamK af Ahm w~ o ad cunio ft Dywm URaw Maido be and to a~"t .immeum a coo mod w~mbe umta mbaww~do aft bte awe Ie a -- dbmw ~ *MffA"Iim-10 @a dm

HTML5 PivotViewer: high-throughput visualization and querying of image data on the web

PubMed Central

Taylor, Stephen; Noble, Roger

2014-01-01

Motivation: Visualization and analysis of large numbers of biological images has generated a bottle neck in research. We present HTML5 PivotViewer, a novel, open source, platform-independent viewer making use of the latest web technologies that allows seamless access to images and associated metadata for each image. This provides a powerful method to allow end users to mine their data. Availability and implementation: Documentation, examples and links to the software are available from http://www.cbrg.ox.ac.uk/data/pivotviewer/. The software is licensed under GPLv2. Contact:  stephen.taylor@imm.ox.ac.uk and roger@coritsu.com PMID:24849578

Mountain Home AFB, Mountain Home, Idaho. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

DTIC Science & Technology

1980-03-10

FEDERAL BUILDING i6W WOMENT M ~A BEEN APMRVED AHVLE .C FOR PUBLIC RELEASE AND SALE- ITS DI.SHEILEN.C -TR-IBUTION IS UNLIMTEW -7 WOI R~eview and A~proval...reduced visibility. -~~ -- 2 - _____ _____ _____ J" M ’LAL CL>v_*T-LCGY FkACil 7; T:4 Sr-~z~ VVJC;/:EATHER CONDITIONS 1 4~1 -GC"C AFi 79 65-77,7- 79 JA ’ S...01-0 5(OL-AuvlwaotoeloFw’omANoc AATro O~ m m -, imm.~-=--~ ~---=~- __41 4- Lc~.L CLIM4TOLOGY BR~ANCH UA T~.ATE C~ Cfl WEATHER CONDITIONS 2____-6

T2 mapping in patellar chondromalacia.

PubMed

Ruiz Santiago, Fernando; Pozuelo Calvo, Rocío; Almansa López, Julio; Guzmán Álvarez, Luis; Castellano García, María Del Mar

2014-06-01

To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia. This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16-45 years). MRI of 97 knees were performed in these patients at 1.5T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet-proximal-lateral (EPL), external facet-proximal-central (EPC), internal facet-proximal-central (IPC), internal facet-proximal-medial (IPM), 4 in the middle section (external facet-middle-lateral (EML), external facet-middle-central (EMC), internal facet-middle-central (IMC), internal facet-middle-medial (IMM) and 4 distal (external facet-distal-lateral (EDL), external facet-distal-central (EDC), internal facet-distal-central (IDC), internal facet-distal-medial (IDM). T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p<0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p<0.05). Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

On-Orbit Measurement of Next Generation Space Solar Cell Technology on the International Space Station

NASA Technical Reports Server (NTRS)

Wolford, David S.; Myers, Matthew G.; Prokop, Norman F.; Krasowski, Michael J.; Parker, David S.; Cassidy, Justin C.; Davies, William E.; Vorreiter, Janelle O.; Piszczor, Michael F.; McNatt, Jeremiah S.

2015-01-01

Measurement is essential for the evaluation of new photovoltaic (PV) technology for space solar cells. NASA Glenn Research Center (GRC) is in the process of measuring several solar cells in a supplemental experiment on NASA Goddard Space Flight Center's (GSFC) Robotic Refueling Mission's (RRM) Task Board 4 (TB4). Four industry and government partners have provided advanced PV devices for measurement and orbital environment testing. The experiment will be on-orbit for approximately 18 months. It is completely self-contained and will provide its own power and internal data storage. Several new cell technologies including four- junction (4J) Inverted Metamorphic Multijunction (IMM) cells will be evaluated and the results compared to ground-based measurements.

Magnetic and transport properties of Ce 6MnSb 15

NASA Astrophysics Data System (ADS)

Godart, Claude; Rogl, Peter; Alleno, Eric; Gonçalves, António P.; Rouleau, Olivier

2006-05-01

In our effort to look for new Ce/Yb-based compounds with large unit cell, we studied Ce 6MnSb 15. Rietveld refinements of X-ray powder diffraction confirm that the material crystallizes in orthorhombic structure La 6MnSb 15-type, Imm2 space group, with 2 Ce sites (8e and 4d) and lattice parameters a=15.1643 Å, b=19.3875 Å and c=4.2794 Å, which closely agree with those already published. Magnetic susceptibility results show a paramagnetic behavior and no magnetic order down to 2 K in contrast to antiferromagnetic order previously reported at 7 K. Resistivity shows a metallic behavior and the Seebeck coefficient is very low, typically -2 μV/K.

Consumers and Workers Opinions of A Proposed Cash Food System: NAS Alameda

DTIC Science & Technology

1975-08-01

J - A August 1975 UNITED STATES ARMY NATO DEVELOPMENT CENTER NATICK, MASSACHUSETTS 01760 Reproduced by NATIONAL...r0im[,m’mw^m^mw&wk!^mmmm’ ■ »-!MM!PW»»* J ^WM*^-»^«^w ■ •. «»q» x.,* ,»^, 8T’<’i’H|gMBai> J ’~"^ ;%»* -« y-’ i: l^laan-tf^wri »tCUWTY...T»?i«n Data Erl.rad) *"--"’—>-n--^a»<fc~mu. ,~ j **- , . ——^ „ .^MMtmmMMM in« in’ ■■- ■ jpplpw(pwflppr*^"’ ’""’»’"» •••-’

Expression of the cloned ColE1 kil gene in normal and Kilr Escherichia coli.

PubMed Central

Altieri, M; Suit, J L; Fan, M L; Luria, S E

1986-01-01

The kil gene of the ColE1 plasmid was cloned under control of the lac promoter. Its expression under this promoter gave rise to the same pattern of bacterial cell damage and lethality as that which accompanies induction of the kil gene in the colicin operon by mitomycin C. This confirms that cell damage after induction is solely due to expression of kil and is independent of the cea or imm gene products. Escherichia coli derivatives resistant to the lethal effects of kil gene expression under either the normal or the lac promoter were isolated and found to fall into several classes, some of which were altered in sensitivity to agents that affect the bacterial envelope. PMID:2946661

[Sarcopenia and functionality in elderly inpatient].

PubMed

Chávez-Moreno, Diana Victoria; Infante-Sierra, Héctor; Serralde-Zúñiga, Aurora E

2015-04-01

Sarcopenia is a geriatric syndrome associated with adverse events. The aim of the present study was to assess the sarcopenia prevalence and its association with the functionality in elderly inpatient. A cross sectional study, during 6 months were included elderly inpatients to determine the presence of sarcopenia using the Baumgartner method. The functionality to perform basic activities of daily living (ABVD) was determined by the Katz index. Student's t test or U de Mann-Whitney was used to assess the differences between two groups and one-factor ANOVA or Kruskal Wallis for multiple comparisons; X2 and Fisher's exact test were used to compare the categorical variables and the Pearson correlation was calculated to determine the correlations between variables. 102 patients were included, 41 women and 61 man; subjects had a mean age of 71±8.6 years, body mass index 27.8±5.2 kg/m2, grip strength 14.9±8.3 kg, appendicular skeletal muscle mass (MMEA) 17.6±4.3 kg and skeletal muscle mass index (IMME) 7.1±1.2 kg/m2. The global prevalence of sarcopenia was 27.5%, was major in men (RR 1.33; CI 95% 1.06-1.67 p<0.05). There was a significant decrease on the grip strength (r=-.341) and MMEA (r=-.231) (p<0.05); sarcopenia was associated to a major dependence in both genders (p<0.05). Sarcopenia is a frequent condition in the elderly inpatients associated with the functionality's deterioration,identifying it help to perform a primary or secondary prevention and opportunity treatment.

Bis[(1S)-1 4-azanediyl-1-(9-deazaadenin-9-yl)-1 4-dideoxy-5-methylsulfanyl-D-ribitol] tetrakis(hydrochloride) monohydrate: structure DFT energy and ligand docking results of a potent methylthioadenosine phosphorylase inhibitor found in different

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

G Gainsford; G Evans; K Johnston

2011-12-31

The title compound, abbreviated as 5'ThiomethylImmA, is a potent inhibitor of methylthioadenosine phosphorylase [Singh et al. (2004). Biochemistry, 43, 9-18]. The synchrotron study reported here shows that the hydrochloride salt crystallizes with two independent, nearly superimposable, dications as a monohydrate with formula 2C{sub 12}H{sub 19}N{sub 5}O{sub 2}S{sup 2+}{center_dot}4Cl{sup -}{center_dot}H{sub 2}O. Hydrogen bonding utilizing the H atoms of the dication is found to favor certain molecular conformations in the salt, which are significantly different from those found as bound in the enzyme. Ligand docking studies starting from either of these dications or related neutral structures successfully place the conformationally revised structuresmore » in the enzyme active site but only under particular hydrogen-bonding and molecular flexibility criteria. Density functional theory calculations verify the energy similarity of the indendent cations and confirm the significant energy cost of the required conformation change to the enzyme bound form. The results suggest the using crystallographically determined free ligand coordinates as starting parameters for modelling may have serious limitations.« less

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

Ouyang, J.H.; Li, X.; Lei, T.C.

The microstructure of a laser-clad TiC-Ni particle-reinforced coating on 1045 steel was studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ion microprobe mass spectroscopy (IMMS). The microstructural constituents of the clad layers (CLs) were analyzed to be TiC particles, {gamma}-Ni primary dendrites, and interdendritic eutectics of {gamma}{sub E}-Ni plus M{sub 23}(CB){sub 6} and M{sub 6}(CB) carboborides. Three growth mechanisms of the original TiC particles were found: (1) stepped lateral growth at the edges, (2) radiated and cylindrically coupled growth at the edges, and (3) bridging growth of the clustered particles. Ordered and modulated structures were found inmore » the original TiC particles. In addition to the original TiC particles, fine TiC particles precipitated from the liquid phase and {gamma}-Ni solid solution during laser cladding. The microstructures of the bonding zones (BZs) were intimately associated with laser processing parameters. The BZs of the clad coatings can be categorized into three types according to the combination of the CL with heat-affected zone (HAZ): (1) straight interface combination, (2) zigzag connection, and (3) combination by partial melting of prior austenitic grain boundaries of the substrate. The microstructural evolution of the CLs was discussed. The formation and phase transformation models of the BZs were proposed.« less

The transcriptional landscape of αβ T cell differentiation

PubMed Central

Mingueneau, Michael; Kreslavsky, Taras; Gray, Daniel; Heng, Tracy; Cruse, Richard; Ericson, Jeffrey; Bendall, Sean; Spitzer, Matt; Nolan, Garry; Kobayashi, Koichi; von Boehmer, Harald; Mathis, Diane; Benoist, Christophe

2013-01-01

αβT cell differentiation from thymic precursors is a complex process, explored here with the breadth of ImmGen expression datasets, analyzing how differentiation of thymic precursors gives rise to transcriptomes. After surprisingly gradual changes though early T commitment, transit through the CD4+CD8+ stage involves a shutdown or rare breadth, and correlating tightly with MYC. MHC-driven selection promotes a large-scale transcriptional reactivation. We identify distinct signatures that mark cells destined for positive selection versus apoptotic deletion. Differential expression of surprisingly few genes accompany CD4 or CD8 commitment, a similarity that carries through to peripheral T cells and their activation, revealed by mass cytometry phosphoproteomics. The novel transcripts identified as candidate mediators of key transitions help define the “known unknown” of thymocyte differentiation. PMID:23644507

Rupture simultanée du ligament croisé antérieur et du ligament patellaire: à propos d'un cas

PubMed Central

Achkoun, Abdessalam; Houjairi, Khalid; Quahtan, Omar; Hassoun, Jalal; Arssi, Mohamed; Rahmi, Mohamed; Garch, Abdelhak

2016-01-01

La rupture simultanée du tendon rotulien et du ligament croisé antérieur est une lésion relativement rare. Son diagnostic peut facilement manquer lors de l'examen initial. Les options de traitement incluent la réparation immédiate du tendon rotulien avec soit la reconstruction simultanée ou différée de ligament croisé antérieur. Nous rapportons le cas d'une rupture combinée du tendon rotulien et du ligament croisé antérieur chez un jeune footballeur de 22 ans. Une approche de traitement en deux temps a été effectuée avec un excellent résultat fonctionnel. PMID:27366288

Characterization of Isolates of Streptococcus agalactiae from Diseased Farmed and Wild Marine Fish from the U.S. Gulf Coast, Latin America, and Thailand.

PubMed

Soto, Esteban; Wang, Rui; Wiles, Judy; Baumgartner, Wes; Green, Christopher; Plumb, John; Hawke, John

2015-06-01

We examined Lancefield serogroup B Streptococcus isolates recovered from diseased, cultured hybrid Striped Bass (Striped Bass Morone saxatilis × White Bass M. chrysops) and wild and cultured Gulf Killifish Fundulus grandis from coastal waters of the U.S. Gulf of Mexico (Gulf coast) and compared those isolates to strains from tilapias Oreochromis spp. reared in Mississippi, Thailand, Ecuador, and Honduras and to the original Gulf coast strain identified by Plumb et al. ( 1974 ). The isolates were subjected to phylogenetic, biochemical, and antibiotic susceptibility analyses. Genetic analysis was performed using partial sequence comparison of (1) the 16S ribosomal RNA (rRNA) gene; (2) the sipA gene, which encodes a surface immunogenic protein; (3) the cspA gene, which encodes a cell surface-associated protein; and (4) the secY gene, which encodes components of a general protein secretion pathway. Phylogenies inferred from sipA, secY, and cspA gene sequence comparisons were more discriminating than that inferred from the 16S rRNA gene sequence comparison. The U.S. Gulf coast strains showed a high degree of similarity to strains from South America and Central America and belonged to a unique group that can be distinguished from other group B streptococci. In agreement with the molecular findings, biochemical and antimicrobial resistance analyses demonstrated that the isolates recovered from the U.S. Gulf coast and Latin America were more similar to each other than to isolates from Thailand. Three laboratory challenge methods for inducing streptococcosis in Gulf Killifish were evaluated-intraperitoneal (IP) injection, immersion (IMM), and immersion plus abrasion (IMMA)-using serial dilutions of S. agalactiae isolate LADL 97-151, a representative U.S. Gulf coast strain. The dose that was lethal to 50% of test fish by 14 d postchallenge was approximately 2 CFU/fish via IP injection. In contrast, the fish that were challenged via IMM or IMMA presented cumulative mortality less than 40% by 14 d postchallenge.

The Eye of the Tiger, the Thrill of the Fight: Effective Larval and Adult Control Measures Against the Asian Tiger Mosquito, Aedes albopictus (Diptera: Culicidae), in North America.

PubMed

Faraji, Ary; Unlu, Isik

2016-09-01

The Asian tiger mosquito, Aedes albopictus (Skuse), is a highly invasive container-inhabiting species with a global distribution. This mosquito, similar to other Stegomyia species such as Aedes aegypti (L.), is highly adapted to urban and suburban areas, and commonly oviposits in artificial containers, which are ubiquitous in these peridomestic environments. The increase in speed and amount of international travel and commerce, coupled with global climate change, have aided in the resurgence and expansion of Stegomyia species into new areas of North America. In many parts of their range, both species are implicated as significant vectors of emerging and re-emerging arboviruses such as dengue, chikungunya, and now Zika. Although rapid and major advances have been made in the field of biology, ecology, genetics, taxonomy, and virology, relatively little has changed in the field of mosquito control in recent decades. This is particularly discouraging in regards to container-inhabiting mosquitoes, because traditional integrated mosquito management (IMM) approaches have not been effective against these species. Many mosquito control programs simply do not possess the man-power or necessary financial resources needed to suppress Ae. albopictus effectively. Therefore, control of mosquito larvae, which is the foundation of IMM approaches, is exceptionally difficult over large areas. This review paper addresses larval habitats, use of geographic information systems for habitat preference detection, door-to-door control efforts, source reduction, direct application of larvicides, biological control agents, area-wide low-volume application of larvicides, hot spot treatments, autodissemination stations, public education, adult traps, attractive-toxic sugar bait methods, lethal ovitraps, barrier-residual adulticides, hand-held ultra-low-volume adulticides, area-wide adulticides applied by ground or air, and genetic control methods. The review concludes with future recommendations for practitioners, researchers, private industry, and policy makers. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the United States.

Hypoxic HepG2 cell adaptation decreases ATP synthase dimers and ATP production in inflated cristae by mitofilin down-regulation concomitant to MICOS clustering.

PubMed

Plecitá-Hlavatá, Lydie; Engstová, Hana; Alán, Lukáš; Špaček, Tomáš; Dlasková, Andrea; Smolková, Katarína; Špačková, Jitka; Tauber, Jan; Strádalová, Vendula; Malínský, Jan; Lessard, Mark; Bewersdorf, Joerg; Ježek, Petr

2016-05-01

The relationship of the inner mitochondrial membrane (IMM) cristae structure and intracristal space (ICS) to oxidative phosphorylation (oxphos) is not well understood. Mitofilin (subunit Mic60) of the mitochondrial contact site and cristae organizing system (MICOS) IMM complex is attached to the outer membrane (OMM) via the sorting and assembly machinery/topogenesis of mitochondrial outer membrane β-barrel proteins (SAM/TOB) complex and controls the shape of the cristae. ATP synthase dimers determine sharp cristae edges, whereas trimeric OPA1 tightens ICS outlets. Metabolism is altered during hypoxia, and we therefore studied cristae morphology in HepG2 cells adapted to 5% oxygen for 72 h. Three dimensional (3D), super-resolution biplane fluorescence photoactivation localization microscopy with Eos-conjugated, ICS-located lactamase-β indicated hypoxic ICS expansion with an unchanged OMM (visualized by Eos-mitochondrial fission protein-1). 3D direct stochastic optical reconstruction microscopy immunocytochemistry revealed foci of clustered mitofilin (but not MICOS subunit Mic19) in contrast to its even normoxic distribution. Mitofilin mRNA and protein decreased by ∼20%. ATP synthase dimers vs monomers and state-3/state-4 respiration ratios were lower during hypoxia. Electron microscopy confirmed ICS expansion (maximum in glycolytic cells), which was absent in reduced or OMM-detached cristae of OPA1- and mitofilin-silenced cells, respectively. Hypoxic adaptation is reported as rounding sharp cristae edges and expanding cristae width (ICS) by partial mitofilin/Mic60 down-regulation. Mitofilin-depleted MICOS detaches from SAM while remaining MICOS with mitofilin redistributes toward higher interdistances. This phenomenon causes partial oxphos dormancy in glycolytic cells via disruption of ATP synthase dimers.-Plecitá-Hlavatá, L., Engstová, H., Alán, L., Špaček, T., Dlasková, A., Smolková, K., Špačková, J., Tauber, J., Strádalová, V., Malínský, J., Lessard, M., Bewersdorf, J., Ježek, P. Hypoxic HepG2 cell adaptation decreases ATP synthase dimers and ATP production in inflated cristae by mitofilin down-regulation concomitant to MICOS clustering. © FASEB.

Time resolved native ion-mobility mass spectrometry to monitor dynamics of IgG4 Fab arm exchange and "bispecific" monoclonal antibody formation.

PubMed

Debaene, François; Wagner-Rousset, Elsa; Colas, Olivier; Ayoub, Daniel; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2013-10-15

Monoclonal antibodies (mAbs) and derivatives such as antibody-drug conjugates (ADC) and bispecific antibodies (bsAb), are the fastest growing class of human therapeutics. Most of the therapeutic antibodies currently on the market and in clinical trials are chimeric, humanized, and human immunoglobulin G1 (IgG1). An increasing number of IgG2s and IgG4s that have distinct structural and functional properties are also investigated to develop products that lack or have diminished antibody effector functions compared to IgG1. Importantly, wild type IgG4 has been shown to form half molecules (one heavy chain and one light chain) that lack interheavy chain disulfide bonds and form intrachain disulfide bonds. Moreover, IgG4 undergoes a process of Fab-arm exchange (FAE) in which the heavy chains of antibodies of different specificities can dissociate and recombine in bispecific antibodies both in vitro and in vivo. Here, native mass spectrometry (MS) and time-resolved traveling wave ion mobility MS (TWIM-MS) were used for the first time for online monitoring of FAE and bsAb formation using Hz6F4-2v3 and natalizumab, two humanized IgG4s which bind to human Junctional Adhesion Molecule-A (JAM-A) and alpha4 integrin, respectively. In addition, native MS analysis of bsAb/JAM-A immune complexes revealed that bsAb can bind up to two antigen molecules, confirming that the Hz6F4 family preferentially binds dimeric JAM-A. Our results illustrate how IM-MS can rapidly assess bsAb structural heterogeneity and be easily implemented into MS workflows for bsAb production follow up and bsAb/antigen complex characterization. Altogether, these results provide new MS-based methodologies for in-depth FAE and bsAb formation monitoring. Native MS and IM-MS will play an increasing role in next generation biopharmaceutical product characterization like bsAbs, antibody mixtures, and antibody-drug conjugates (ADC) as well as for biosimilar and biobetter antibodies.

Exactly energy conserving semi-implicit particle in cell formulation

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

Lapenta, Giovanni, E-mail: giovanni.lapenta@kuleuven.be

We report a new particle in cell (PIC) method based on the semi-implicit approach. The novelty of the new method is that unlike any of its semi-implicit predecessors at the same time it retains the explicit computational cycle and conserves energy exactly. Recent research has presented fully implicit methods where energy conservation is obtained as part of a non-linear iteration procedure. The new method (referred to as Energy Conserving Semi-Implicit Method, ECSIM), instead, does not require any non-linear iteration and its computational cycle is similar to that of explicit PIC. The properties of the new method are: i) it conservesmore » energy exactly to round-off for any time step or grid spacing; ii) it is unconditionally stable in time, freeing the user from the need to resolve the electron plasma frequency and allowing the user to select any desired time step; iii) it eliminates the constraint of the finite grid instability, allowing the user to select any desired resolution without being forced to resolve the Debye length; iv) the particle mover has a computational complexity identical to that of the explicit PIC, only the field solver has an increased computational cost. The new ECSIM is tested in a number of benchmarks where accuracy and computational performance are tested. - Highlights: • We present a new fully energy conserving semi-implicit particle in cell (PIC) method based on the implicit moment method (IMM). The new method is called Energy Conserving Implicit Moment Method (ECIMM). • The novelty of the new method is that unlike any of its predecessors at the same time it retains the explicit computational cycle and conserves energy exactly. • The new method is unconditionally stable in time, freeing the user from the need to resolve the electron plasma frequency. • The new method eliminates the constraint of the finite grid instability, allowing the user to select any desired resolution without being forced to resolve the Debye length. • These features are achieved at a reduced cost compared with either previous IMM or fully implicit implementation of PIC.« less

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

Ho, M.; Shi, W; Rinaldo-Mathis, A

Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide asmore » the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.« less

Immersive virtual reality as a teaching tool for neuroanatomy.

PubMed

Stepan, Katelyn; Zeiger, Joshua; Hanchuk, Stephanie; Del Signore, Anthony; Shrivastava, Raj; Govindaraj, Satish; Iloreta, Alfred

2017-10-01

Three-dimensional (3D) computer modeling and interactive virtual reality (VR) simulation are validated teaching techniques used throughout medical disciplines. Little objective data exists supporting its use in teaching clinical anatomy. Learner motivation is thought to limit the rate of utilization of such novel technologies. The purpose of this study is to evaluate the effectiveness, satisfaction, and motivation associated with immersive VR simulation in teaching medical students neuroanatomy. Images of normal cerebral anatomy were reconstructed from human Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) imaging and magnetic resonance imaging (MRI) into 3D VR formats compatible with the Oculus Rift VR System, a head-mounted display with tracking capabilities allowing for an immersive VR experience. The ventricular system and cerebral vasculature were highlighted and labeled to create a focused interactive model. We conducted a randomized controlled study with 66 medical students (33 in both the control and experimental groups). Pertinent neuroanatomical structures were studied using either online textbooks or the VR interactive model, respectively. We then evaluated the students' anatomy knowledge, educational experience, and motivation (using the Instructional Materials Motivation Survey [IMMS], a previously validated assessment). There was no significant difference in anatomy knowledge between the 2 groups on preintervention, postintervention, or retention quizzes. The VR group found the learning experience to be significantly more engaging, enjoyable, and useful (all p < 0.01) and scored significantly higher on the motivation assessment (p < 0.01). Immersive VR educational tools awarded a more positive learner experience and enhanced student motivation. However, the technology was equally as effective as the traditional text books in teaching neuroanatomy. © 2017 ARS-AAOA, LLC.

Gas-Phase Analysis of the Complex of Fibroblast GrowthFactor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study

NASA Astrophysics Data System (ADS)

Zhao, Yuejie; Singh, Arunima; Xu, Yongmei; Zong, Chengli; Zhang, Fuming; Boons, Geert-Jan; Liu, Jian; Linhardt, Robert J.; Woods, Robert J.; Amster, I. Jonathan

2017-01-01

Fibroblast growth factors (FGFs) regulate several cellular developmental processes by interacting with cell surface heparan proteoglycans and transmembrane cell surface receptors (FGFR). The interaction of FGF with heparan sulfate (HS) is known to induce protein oligomerization, increase the affinity of FGF towards its receptor FGFR, promoting the formation of the HS-FGF-FGFR signaling complex. Although the role of HS in the signaling pathways is well recognized, the details of FGF oligomerization and formation of the ternary signaling complex are still not clear, with several conflicting models proposed in literature. Here, we examine the effect of size and sulfation pattern of HS upon FGF1 oligomerization, binding stoichiometry and conformational stability, through a combination of ion mobility (IM) and theoretical modeling approaches. Ion mobility-mass spectrometry (IMMS) of FGF1 in the presence of several HS fragments ranging from tetrasaccharide (dp4) to dodecasaccharide (dp12) in length was performed. A comparison of the binding stoichiometry of variably sulfated dp4 HS to FGF1 confirmed the significance of the previously known high-affinity binding motif in FGF1 dimerization, and demonstrated that certain tetrasaccharide-length fragments are also capable of inducing dimerization of FGF1. The degree of oligomerization was found to increase in the presence of dp12 HS, and a general lack of specificity for longer HS was observed. Additionally, collision cross-sections (CCSs) of several FGF1-HS complexes were calculated, and were found to be in close agreement with experimental results. Based on the (CCSs) a number of plausible binding modes of 2:1 and 3:1 FGF1-HS are proposed.

NASA Glenn Research Center Solar Cell Experiment Onboard the International Space Station

NASA Technical Reports Server (NTRS)

Myers, Matthew G.; Wolford, David S.; Prokop, Norman F.; Krasowski, Michael J.; Parker, David S.; Cassidy, Justin C.; Davies , William E.; Vorreiter, Janelle O.; Piszczor, Michael F.; Mcnatt, Jeremiah S.;

A Hybrid Method Which Combines a Moment Method Current with an Asymptotic Current

DTIC Science & Technology

1981-05-01

s op SinceJp(x) in Equation (2.12) and Jp(R) in Equation (2.14) op op are approximations for Vt(K) and jS(f), respectively...approxi- mations for TM(R) and ImM can be written as 2 W f T M(R’)xV’G(r)ds’ + 2x TsM( ’)xV’G(r)ds’ MM St MS MM M + 2nix f iSp (R’)xv’G(r)ds’ (2.29) s op and...8217 (2.37) Jp(R) = 2fi’(R) + 2^nx fI ( pI)xv’G(r)ds’ op top + 2’x i s (R’)xV’G(r)ds’ (2.38) s op 20 .;ALI T;()= 2Rx f

Thrombophlébite cérébrale inhabituelle du post-partum

PubMed Central

El Hassani, Moulay Elmehdi; Habib, Abdellah Baba; Kouach, Jaouad; Sekkach, Youssef; Bakkali, Hicham; Jira, Mohamed; Elqatni, Mohamed; Abouzahir, Ali; Ghafir, Dris; Moussaoui, Dris; Dehayni, Mohamed

2014-01-01

La thrombophlébite cérébrale du post-partum immédiat constitue un événement rare et gravissime pouvant mettre en jeu le pronostic vital à court terme. Celle-ci doit être systématiquement évoquée devant la persistance d'une fièvre dans les suites de couches. La prise en charge associera le plus souvent, des antibiotiques à large spectre et des anticoagulants. Le suivi évolutif est indispensable, afin d'apprécier l'efficacité thérapeutique. A travers une observation singulière et à présentation inhabituelle, nous insistons sur le grand intérêt des moyens d'imagerie dont nous disposons afin de porter le diagnostic et de choisir le traitement le mieux adapté. PMID:25478039

ExMC Work Prioritization Process

NASA Technical Reports Server (NTRS)

Simon, Matthew

2015-01-01

Last year, NASA's Human Research Program (HRP) introduced the concept of a "Path to Risk Reduction" (PRR), which will provide a roadmap that shows how the work being done within each HRP element can be mapped to reducing or closing exploration risks. Efforts are currently underway within the Exploration Medical Capability (ExMC) Element to develop a structured, repeatable process for prioritizing work utilizing decision analysis techniques and risk estimation tools. The goal of this effort is to ensure that the work done within the element maximizes risk reduction for future exploration missions in a quantifiable way and better aligns with the intent and content of the Path to Risk Reduction. The Integrated Medical Model (IMM) will be used to identify those conditions that are major contributors of medical risk for a given design reference mission. For each of these conditions, potential prevention, screening, diagnosis, and treatment methods will be identified. ExMC will then aim to prioritize its potential investments in these mitigation methods based upon their potential for risk reduction and other factors such as vehicle performance impacts, near term schedule needs, duplication with external efforts, and cost. This presentation will describe the process developed to perform this prioritization and inform investment discussions in future element planning efforts. It will also provide an overview of the required input information, types of process participants, figures of merit, and the expected outputs of the process.

The Extravehicular Suit Impact Load Attenuation Study for Use in Astronaut Bone Fracture Prediction

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Gilkey, Kelly M.; Sulkowski, Christina M.; Samorezov, Sergey; Myers, Jerry G.

2011-01-01

The NASA Integrated Medical Model (IMM) assesses the risk, including likelihood and impact of occurrence, of all credible in-flight medical conditions. Fracture of the proximal femur is a traumatic injury that would likely result in loss of mission if it were to happen during spaceflight. The low gravity exposure causes decreases in bone mineral density which heightens the concern. Researchers at the NASA Glenn Research Center have quantified bone fracture probability during spaceflight with a probabilistic model. It was assumed that a pressurized extravehicular activity (EVA) suit would attenuate load during a fall, but no supporting data was available. The suit impact load attenuation study was performed to collect analogous data. METHODS: A pressurized EVA suit analog test bed was used to study how the offset, defined as the gap between the suit and the astronaut s body, impact load magnitude and suit operating pressure affects the attenuation of impact load. The attenuation data was incorporated into the probabilistic model of bone fracture as a function of these factors, replacing a load attenuation value based on commercial hip protectors. RESULTS: Load attenuation was more dependent on offset than on pressurization or load magnitude, especially at small offsets. Load attenuation factors for offsets between 0.1 - 1.5 cm were 0.69 +/- 0.15, 0.49 +/- 0.22 and 0.35 +/- 0.18 for mean impact forces of 4827, 6400 and 8467 N, respectively. Load attenuation factors for offsets of 2.8 - 5.3 cm were 0.93 +/- 0.2, 0.94 +/- 0.1 and 0.84 +/- 0.5, for the same mean impact forces. Reductions were observed in the 95th percentile confidence interval of the bone fracture probability predictions. CONCLUSIONS: The reduction in uncertainty and improved confidence in bone fracture predictions increased the fidelity and credibility of the fracture risk model and its benefit to mission design and operational decisions.

Further Analyses of the NASA Glenn Research Center Solar Cell and Photovoltaic Materials Experiment Onboard the International Space Station

NASA Technical Reports Server (NTRS)

Myers, Matthew G.; Prokop, Norman F.; Krasowski, Michael J.; Piszczor, Michael F.; McNatt, Jeremiah S.

2016-01-01

Accurate air mass zero (AM0) measurement is essential for the evaluation of new photovoltaic (PV) technology for space solar cells. The NASA Glenn Research Center (GRC) has flown an experiment designed to measure the electrical performance of several solar cells onboard NASA Goddard Space Flight Center's (GSFC) Robotic Refueling Mission's (RRM) Task Board 4 (TB4) on the exterior of the International Space Station (ISS). Four industry and government partners provided advanced PV devices for measurement and orbital environment testing. The experiment was positioned on the exterior of the station for approximately eight months, and was completely self-contained, providing its own power and internal data storage. Several new cell technologies including four-junction (4J) Inverted Metamorphic Multi-Junction (IMM) cells were evaluated and the results will be compared to ground-based measurement methods.

Evaluation of a Test Article in the Salmonella typhimurium/Escherichia coli Plate Incorporation Mutation Assay in the Presence and Absence of Induced Rat Liver S-9. Test Article: N,N,N’,N’-tetramethyl ethanediamine (TMEDA)

DTIC Science & Technology

2008-06-12

15 14 15 STANDARD DEVIATION (:1:) 3 5 4 4 4 MINIMUM VALUE 9 12 11 8 10 MAXIMUM VALUE 20 33 23 29 24 N" 56 19 14 38 28 IMm ~ ~ CORN Oil l:W...AVERAGE 9 9 10 8 9 STANDARD DEVIATION (:1:) 3 3 4 2 3 MINIMUM VAlUE 2 6 3 5 4 MAXIMUM VAlUE 20 16 23 12 15 N" 65 21 14 33 29 E.COLI DMSO ~ CORN ...21 33 25 21 23 N* 66 19 14 38 28 :wm ~ ACET CORN Oil !L!! SAUNE AVERAGE 9 10 10 9 8 STANDARD DEVlA.11ON (:I:) 3 3 4 3 2 MINIMUM VAWS . 4 6 6 6 3

Electrical Resistivity of Wire Arc Sprayed Zn and Cu Coatings for In-Mold-Metal-Spraying

NASA Astrophysics Data System (ADS)

Bobzin, K.; Öte, M.; Knoch, M. A.; Liao, X.; Hopmann, Ch; Ochotta, P.

2018-06-01

Electrical functionalities can be integrated into plastic parts by integrating thermally sprayed metal coatings into the non-conductive base material. Thermally sprayed conducting tracks for power and signal transmission are one example. In this case, the electrical resistance or resistivity of the coatings should be investigated. Therefore, the electrical resistivity of wire arc sprayed Zn and Cu coatings has been investigated. In case of Zn coatings, spray distance, gas pressure and wire diameter could be identified as significant influencing parameters on the electrical resistivity. In contrast, process gas, gas pressure and voltage do have a significant influence on the electrical resistivity of Cu coatings. Through the use of the In-Mold-Metal-Spraying method (IMMS), thermal degradation can be avoided by transferring thermally sprayed coating from a mold insert onto the plastic part. Therefore, the influence of the transfer process on the electrical resistance of the coatings has also been investigated.

Electronic single-molecule identification of carbohydrate isomers by recognition tunnelling

NASA Astrophysics Data System (ADS)

Im, Jongone; Biswas, Sovan; Liu, Hao; Zhao, Yanan; Sen, Suman; Biswas, Sudipta; Ashcroft, Brian; Borges, Chad; Wang, Xu; Lindsay, Stuart; Zhang, Peiming

2016-12-01

Carbohydrates are one of the four main building blocks of life, and are categorized as monosaccharides (sugars), oligosaccharides and polysaccharides. Each sugar can exist in two alternative anomers (in which a hydroxy group at C-1 takes different orientations) and each pair of sugars can form different epimers (isomers around the stereocentres connecting the sugars). This leads to a vast combinatorial complexity, intractable to mass spectrometry and requiring large amounts of sample for NMR characterization. Combining measurements of collision cross section with mass spectrometry (IM-MS) helps, but many isomers are still difficult to separate. Here, we show that recognition tunnelling (RT) can classify many anomers and epimers via the current fluctuations they produce when captured in a tunnel junction functionalized with recognition molecules. Most importantly, RT is a nanoscale technique utilizing sub-picomole quantities of analyte. If integrated into a nanopore, RT would provide a unique approach to sequencing linear polysaccharides.

Shared decision-making in medication management: development of a training intervention

PubMed Central

Stead, Ute; Morant, Nicola; Ramon, Shulamit

2017-01-01

Shared decision-making is a collaborative process in which clinicians and patients make treatment decisions together. Although it is considered essential to patient-centred care, the adoption of shared decision-making into routine clinical practice has been slow, and there is a need to increase implementation. This paper describes the development and delivery of a training intervention to promote shared decision-making in medication management in mental health as part of the Shared Involvement in Medication Management Education (ShIMME) project. Three stakeholder groups (service users, care coordinators and psychiatrists) received training in shared decision-making, and their feedback was evaluated. The programme was mostly well received, with all groups rating interaction with peers as the best aspect of the training. This small-scale pilot shows that it is feasible to deliver training in shared decision-making to several key stakeholders. Larger studies will be required to assess the effectiveness of such training. PMID:28811918

Shared decision-making in medication management: development of a training intervention.

PubMed

Stead, Ute; Morant, Nicola; Ramon, Shulamit

2017-08-01

Shared decision-making is a collaborative process in which clinicians and patients make treatment decisions together. Although it is considered essential to patient-centred care, the adoption of shared decision-making into routine clinical practice has been slow, and there is a need to increase implementation. This paper describes the development and delivery of a training intervention to promote shared decision-making in medication management in mental health as part of the Shared Involvement in Medication Management Education (ShIMME) project. Three stakeholder groups (service users, care coordinators and psychiatrists) received training in shared decision-making, and their feedback was evaluated. The programme was mostly well received, with all groups rating interaction with peers as the best aspect of the training. This small-scale pilot shows that it is feasible to deliver training in shared decision-making to several key stakeholders. Larger studies will be required to assess the effectiveness of such training.

A matrix-free implicit unstructured multigrid finite volume method for simulating structural dynamics and fluid structure interaction

NASA Astrophysics Data System (ADS)

Lv, X.; Zhao, Y.; Huang, X. Y.; Xia, G. H.; Su, X. H.

2007-07-01

A new three-dimensional (3D) matrix-free implicit unstructured multigrid finite volume (FV) solver for structural dynamics is presented in this paper. The solver is first validated using classical 2D and 3D cantilever problems. It is shown that very accurate predictions of the fundamental natural frequencies of the problems can be obtained by the solver with fast convergence rates. This method has been integrated into our existing FV compressible solver [X. Lv, Y. Zhao, et al., An efficient parallel/unstructured-multigrid preconditioned implicit method for simulating 3d unsteady compressible flows with moving objects, Journal of Computational Physics 215(2) (2006) 661-690] based on the immersed membrane method (IMM) [X. Lv, Y. Zhao, et al., as mentioned above]. Results for the interaction between the fluid and an immersed fixed-free cantilever are also presented to demonstrate the potential of this integrated fluid-structure interaction approach.

The 2006 Java Earthquake revealed by the broadband seismograph network in Indonesia

NASA Astrophysics Data System (ADS)

Nakano, M.; Kumagai, H.; Miyakawa, K.; Yamashina, T.; Inoue, H.; Ishida, M.; Aoi, S.; Morikawa, N.; Harjadi, P.

2006-12-01

On May 27, 2006, local time, a moderate-size earthquake (Mw=6.4) occurred in central Java. This earthquake caused severe damages near Yogyakarta City, and killed more than 5700 people. To estimate the source mechanism and location of this earthquake, we performed a waveform inversion of the broadband seismograms recorded by a nationwide seismic network in Indonesia (Realtime-JISNET). Realtime-JISNET is a part of the broadband seismograph network developed by an international cooperation among Indonesia, Germany, China, and Japan, aiming at improving the capabilities to monitor seismic activity and tsunami generation in Indonesia. 12 stations in Realitme-JISNET were in operation when the earthquake occurred. We used the three-component seismograms from the two closest stations, which were located about 100 and 300 km from the source. In our analysis, we assumed pure double couple as the source mechanism, thus reducing the number of free parameters in the waveform inversion. Therefore we could stably estimate the source mechanism using the signals observed by a small number of seismic stations. We carried out a grid search with respect to strike, dip, and rake angles to investigate fault orientation and slip direction. We determined source-time functions of the moment-tensor components in the frequency domain for each set of strike, dip, and rake angles. We also conducted a spatial grid search to find the best-fit source location. The best-fit source was approximately 12 km SSE of Yogyakarta at a depth of 10 km below sea level, immediately below the area of extensive damage. The focal mechanism indicates that this earthquake was caused by compressive stress in the NS direction and strike-slip motion was dominant. The moment magnitude (Mw) was 6.4. We estimated the seismic intensity in the areas of severe damage using the source paramters and an empirical attenuation relation for averaged peak ground velocity (PGV) of horizontal seismic motion. We then calculated the instrumental modified Mercalli intensity (Imm) from the estimated PGV values. Our result indicates that strong ground motion with Imm of 7 or more occurred within 10 km of the earthquake fault, although the actual seismic intensity can be affected by shallow structural heterogeneity. We therefore conclude that the severe damages of the Java earthquake are attributed to the strong ground motion, which was primarily caused by the source located immediately below the populated areas.

Assessment of beverage intake and hydration status.

PubMed

Nissensohn, Mariela; López-Ufano, Marisa; Castro-Quezada, Itandehui; Serra-Majem, Lluis

2015-02-26

Water is the main constituent of the human body. It is involved in practically all its functions. It is particularly important for thermoregulation and in the physical and cognitive performance. Water balance reflects water intake and loss. Intake of water is done mainly through consumption of drinking water and beverages (70 to 80%) plus water containing foods (20 to 30%). Water loss is mainly due to excretion of water in urine, faeces and sweat. The interest in the type and quantity of beverage consumption is not new, and numerous approaches have been used to assess beverage intake, but the validity of these approaches has not been well established. There is no standardized questionnaire developed as a research tool for the evaluation of water intake in the general population. Sometimes, the information comes from different sources or from different methodological characteristics which raises problems of the comparability. In the European Union, current epidemiological studies that focus exclusively on beverage intake are scarce. Biomarkers of intake are able to objectively assess dietary intake/status without the bias of self-reported dietary intake errors and also overcome the problem of intra-individual diet variability. Furthermore, some methods of measuring dietary intake used biomarkers to validate the data it collects. Biological markers may offer advantages and be able to improve the estimates of dietary intake assessment, which impact into the statistical power of the study. There is a surprising paucity of studies that systematically examine the correlation of beverages intake and hydration biomarker in different populations. A pilot investigation was developed to evaluate the comparative validity and reliability of newly developed interactive multimedia (IMM) versions compared to validated paper-administered (PP) versions of the Hedrick et al. beverage questionnaire. The study showed that the IMM appears to be a valid and reliable measure to assess habitual beverage intake. Similar study was developed in China, but in this case, the use of Smartphone technology was employed for beverage assessment. The methodology for measuring beverage intake in population studies remains controversial. There are few validated and reproducible studies, so there is still lacking an ideal method (ie, short, easy to administer, inexpensive and accurate) in this regard. Clearly, this is an area of scientific interest that is still in development and seems to be very promising for improving health research. Copyright AULA MEDICA EDICIONES 2015. Published by AULA MEDICA. All rights reserved.

Treatment of childhood encopresis: a randomized trial comparing three treatment protocols.

PubMed

Borowitz, Stephen M; Cox, Daniel J; Sutphen, James L; Kovatchev, Boris

2002-04-01

To compare short- and long-term effectiveness of three additive treatment protocols in children experiencing chronic encopresis. Children, 6 to 15 years of age, who experienced at least weekly fecal soiling for 6 months or longer were eligible for the study. Children were randomly assigned to a group that received intensive medical therapy (IMT), a group that received intensive medical therapy plus a behavior management program called enhanced toilet training (ETT), or a group that received intensive medical therapy with enhanced toilet training and external anal sphincter electromyographic biofeedback (BF). Data concerning toileting habits were collected for 14 consecutive days before an initial visit, and at 3, 6, and 12 months after initiation of therapy. All data were collected using a computerized voice-mail system that telephoned the families each day. At 12 months, children were classified as significantly improved (reduction in soiling, P < 0.001) or cured ( 0.90, P < 0.001 in each case). Response to treatment during the first 2 weeks of therapy was highly predictive of outcome at 3, 6, and 12 months (P < 0.0001). Children in the ETT group used less laxative medication (P < 0.04) and required fewer treatment contacts (P = 0.08) than children in the IMM group. All three treatments resulted in significant increases in daily bowel movements passed in the toilet and self-initiated toileting, and resulted in decreases in average daily soiling at 3, 6, and 12 months (P < 0.05). Enhanced toilet training is somewhat more effective in treating childhood encopresis than either intensive medical therapy or anal sphincter biofeedback therapy. Although similar total cure rates at 1 year can be expected with these three forms of therapy, enhanced toilet training results in statistically significant decreases in the daily frequency of soiling for the greatest number of children.

The Tohoku Medical Megabank Project: Design and Mission.

PubMed

Kuriyama, Shinichi; Yaegashi, Nobuo; Nagami, Fuji; Arai, Tomohiko; Kawaguchi, Yoshio; Osumi, Noriko; Sakaida, Masaki; Suzuki, Yoichi; Nakayama, Keiko; Hashizume, Hiroaki; Tamiya, Gen; Kawame, Hiroshi; Suzuki, Kichiya; Hozawa, Atsushi; Nakaya, Naoki; Kikuya, Masahiro; Metoki, Hirohito; Tsuji, Ichiro; Fuse, Nobuo; Kiyomoto, Hideyasu; Sugawara, Junichi; Tsuboi, Akito; Egawa, Shinichi; Ito, Kiyoshi; Chida, Koichi; Ishii, Tadashi; Tomita, Hiroaki; Taki, Yasuyuki; Minegishi, Naoko; Ishii, Naoto; Yasuda, Jun; Igarashi, Kazuhiko; Shimizu, Ritsuko; Nagasaki, Masao; Koshiba, Seizo; Kinoshita, Kengo; Ogishima, Soichi; Takai-Igarashi, Takako; Tominaga, Teiji; Tanabe, Osamu; Ohuchi, Noriaki; Shimosegawa, Toru; Kure, Shigeo; Tanaka, Hiroshi; Ito, Sadayoshi; Hitomi, Jiro; Tanno, Kozo; Nakamura, Motoyuki; Ogasawara, Kuniaki; Kobayashi, Seiichiro; Sakata, Kiyomi; Satoh, Mamoru; Shimizu, Atsushi; Sasaki, Makoto; Endo, Ryujin; Sobue, Kenji; Tohoku Medical Megabank Project Study Group, The; Yamamoto, Masayuki

2016-09-05

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.

Evolution post-opératoire des séquelles de tuberculose pulmonaire chez les séropositifs VIH

PubMed Central

Grégoire, Ayegnon Kouakou; Flavien, Kendja Hypolite; Raphaël, Ouédé; Démine, Blaise; Christophe, Ménéas Gueu; Marie, Ano Kounangui; Hervé, Yangni-Angaté Koffi; Yves, Tanauh

2014-01-01

Cette étude rapporte les aspects cliniques et évolutifs des séquelles pulmonaires tuberculeuses (SPT) opérées chez les séropositifs (VIH+). Il s'agit d'une étude prospective transversale réalisée entre Novembre 2005 et Octobre 2012. Elle a porté sur 20 patients VIH+, ayant dans leurs antécédents, une tuberculose pulmonaire (TP) traitée et déclarée guérie, et admise dans ladite période pour une chirurgie de la SPT secondaire. Une enquête sérologique VIH a été réalisée systématiquement au cours du bilan pré-opératoire. Le diagnostic pré-opératoire de la SPT, la mortalité, les complications post- opératoires (CPOP), le séjour hospitalier, le suivi à moyen terme des STP opérées ont été évalués. Les séropositifs étaient VIH1+ (n = 12; 60%), VIH1&2+ (n = 4; 20%) et VIH2+ (n = 4; 20%). La durée moyenne d’évolution des STP était de 26,22 ± 21,3 mois. Les STP étaient les pyothorax ou pleurésies enkystées (n = 16; 80%), le poumon détruit (n = 2;10%) et les dilatations de bronches (n = 2;10%). Les VIH+ ne présentaient pas d'aspergillome pulmonaire. Le séjour hospitalier moyen était 13,1 ± 10,2 jours. Le suivi total était de 82 patients-année avec une moyenne de suivi de 4,2 ± 2,3 ans (extrêmes: 1 et 7 ans). Le taux de mortalité à court et moyen terme était nul. Aucun décès post-opératoire immédiat n'a été noté. Les CPOP immédiates étaient les bullages prolongés chez 75% des immunodéprimés. Les CPOP tardives (n = 3) étaient un syndrome restrictif pulmonaire, un pyothorax persistant et une pachypleurite résiduelle restrictive. A court terme, le taux de guérison radiologique était de 80% (n = 16). PMID:24932331

Accurate continuous geographic assignment from low- to high-density SNP data.

PubMed

Guillot, Gilles; Jónsson, Hákon; Hinge, Antoine; Manchih, Nabil; Orlando, Ludovic

2016-04-01

Large-scale genotype datasets can help track the dispersal patterns of epidemiological outbreaks and predict the geographic origins of individuals. Such genetically-based geographic assignments also show a range of possible applications in forensics for profiling both victims and criminals, and in wildlife management, where poaching hotspot areas can be located. They, however, require fast and accurate statistical methods to handle the growing amount of genetic information made available from genotype arrays and next-generation sequencing technologies. We introduce a novel statistical method for geopositioning individuals of unknown origin from genotypes. Our method is based on a geostatistical model trained with a dataset of georeferenced genotypes. Statistical inference under this model can be implemented within the theoretical framework of Integrated Nested Laplace Approximation, which represents one of the major recent breakthroughs in statistics, as it does not require Monte Carlo simulations. We compare the performance of our method and an alternative method for geospatial inference, SPA in a simulation framework. We highlight the accuracy and limits of continuous spatial assignment methods at various scales by analyzing genotype datasets from a diversity of species, including Florida Scrub-jay birds Aphelocoma coerulescens, Arabidopsis thaliana and humans, representing 41-197,146 SNPs. Our method appears to be best suited for the analysis of medium-sized datasets (a few tens of thousands of loci), such as reduced-representation sequencing data that become increasingly available in ecology. http://www2.imm.dtu.dk/∼gigu/Spasiba/ gilles.b.guillot@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Immunostaining of dissected zebrafish embryonic heart.

PubMed

Yang, Jingchun; Xu, Xiaolei

2012-01-10

Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments

DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κB p50 Transcription Factor

NASA Astrophysics Data System (ADS)

Vonderach, Matthias; Byrne, Dominic P.; Barran, Perdita E.; Eyers, Patrick A.; Eyers, Claire E.

2018-06-01

The NF-κB transcription factors are known to be extensively phosphorylated, with dynamic site-specific modification regulating their ability to dimerize and interact with DNA. p50, the proteolytic product of p105 (NF-κB1), forms homodimers that bind DNA but lack intrinsic transactivation function, functioning as repressors of transcription from κB promoters. Here, we examine the roles of specific phosphorylation events catalysed by either protein kinase A (PKAc) or Chk1, in regulating the functions of p50 homodimers. LC-MS/MS analysis of proteolysed p50 following in vitro phosphorylation allows us to define Ser328 and Ser337 as PKAc- and Chk1-mediated modifications, and pinpoint an additional four Chk1 phosphosites: Ser65, Thr152, Ser242 and Ser248. Native mass spectrometry (MS) reveals Chk1- and PKAc-regulated disruption of p50 homodimer formation through Ser337. Additionally, we characterise the Chk1-mediated phosphosite, Ser242, as a regulator of DNA binding, with a S242D p50 phosphomimetic exhibiting a > 10-fold reduction in DNA binding affinity. Conformational dynamics of phosphomimetic p50 variants, including S242D, are further explored using ion-mobility MS (IM-MS). Finally, comparative theoretical modelling with experimentally observed p50 conformers, in the absence and presence of DNA, reveals that the p50 homodimer undergoes conformational contraction during electrospray ionisation that is stabilised by complex formation with κB DNA.

Native tandem and ion mobility mass spectrometry highlight structural and modular similarities in clustered-regularly-interspaced shot-palindromic-repeats (CRISPR)-associated protein complexes from Escherichia coli and Pseudomonas aeruginosa.

PubMed

van Duijn, Esther; Barbu, Ioana M; Barendregt, Arjan; Jore, Matthijs M; Wiedenheft, Blake; Lundgren, Magnus; Westra, Edze R; Brouns, Stan J J; Doudna, Jennifer A; van der Oost, John; Heck, Albert J R

2012-11-01

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) immune system of bacteria and archaea provides acquired resistance against viruses and plasmids, by a strategy analogous to RNA-interference. Key components of the defense system are ribonucleoprotein complexes, the composition of which appears highly variable in different CRISPR/Cas subtypes. Previous studies combined mass spectrometry, electron microscopy, and small angle x-ray scattering to demonstrate that the E. coli Cascade complex (405 kDa) and the P. aeruginosa Csy-complex (350 kDa) are similar in that they share a central spiral-shaped hexameric structure, flanked by associating proteins and one CRISPR RNA. Recently, a cryo-electron microscopy structure of Cascade revealed that the CRISPR RNA molecule resides in a groove of the hexameric backbone. For both complexes we here describe the use of native mass spectrometry in combination with ion mobility mass spectrometry to assign a stable core surrounded by more loosely associated modules. Via computational modeling subcomplex structures were proposed that relate to the experimental IMMS data. Despite the absence of obvious sequence homology between several subunits, detailed analysis of sub-complexes strongly suggests analogy between subunits of the two complexes. Probing the specific association of E. coli Cascade/crRNA to its complementary DNA target reveals a conformational change. All together these findings provide relevant new information about the potential assembly process of the two CRISPR-associated complexes.

Online Hydrogen-Deuterium Exchange Traveling Wave Ion Mobility Mass Spectrometry (HDX-IM-MS): a Systematic Evaluation

NASA Astrophysics Data System (ADS)

Cryar, Adam; Groves, Kate; Quaglia, Milena

2017-06-01

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is an important tool for measuring and monitoring protein structure. A bottom-up approach to HDX-MS provides peptide level deuterium uptake values and a more refined localization of deuterium incorporation compared with global HDX-MS measurements. The degree of localization provided by HDX-MS is proportional to the number of peptides that can be identified and monitored across an exchange experiment. Ion mobility spectrometry (IMS) has been shown to improve MS-based peptide analysis of biological samples through increased separation capacity. The integration of IMS within HDX-MS workflows has been commercialized but presently its adoption has not been widespread. The potential benefits of IMS, therefore, have not yet been fully explored. We herein describe a comprehensive evaluation of traveling wave ion mobility integrated within an online-HDX-MS system and present the first reported example of UDMSE acquisition for HDX analysis. Instrument settings required for optimal peptide identifications are described and the effects of detector saturation due to peak compression are discussed. A model system is utilized to confirm the comparability of HDX-IM-MS and HDX-MS uptake values prior to an evaluation of the benefits of IMS at increasing sample complexity. Interestingly, MS and IM-MS acquisitions were found to identify distinct populations of peptides that were unique to the respective methods, a property that can be utilized to increase the spatial resolution of HDX-MS experiments by >60%. [Figure not available: see fulltext.

The Motivated Strategies for Learning Questionnaire: score validity among medicine residents.

PubMed

Cook, David A; Thompson, Warren G; Thomas, Kris G

2011-12-01

The Motivated Strategies for Learning Questionnaire (MSLQ) purports to measure motivation using the expectancy-value model. Although it is widely used in other fields, this instrument has received little study in health professions education. The purpose of this study was to evaluate the validity of MSLQ scores. We conducted a validity study evaluating the relationships of MSLQ scores to other variables and their internal structure (reliability and factor analysis). Participants included 210 internal medicine and family medicine residents participating in a web-based course on ambulatory medicine at an academic medical centre. Measurements included pre-course MSLQ scores, pre- and post-module motivation surveys, post-module knowledge test and post-module Instructional Materials Motivation Survey (IMMS) scores. Internal consistency was universally high for all MSLQ items together (Cronbach's α = 0.93) and for each domain (α ≥ 0.67). Total MSLQ scores showed statistically significant positive associations with post-test knowledge scores. For example, a 1-point rise in total MSLQ score was associated with a 4.4% increase in post-test scores (β = 4.4; p < 0.0001). Total MSLQ scores showed moderately strong, statistically significant associations with several other measures of effort, motivation and satisfaction. Scores on MSLQ domains demonstrated associations that generally aligned with our hypotheses. Self-efficacy and control of learning belief scores demonstrated the strongest domain-specific relationships with knowledge scores (β = 2.9 for both). Confirmatory factor analysis showed a borderline model fit. Follow-up exploratory factor analysis revealed the scores of five factors (self-efficacy, intrinsic interest, test anxiety, extrinsic goals, attribution) demonstrated psychometric and predictive properties similar to those of the original scales. Scores on the MSLQ are reliable and predict meaningful outcomes. However, the factor structure suggests a simplified model might better fit the empiric data. Future research might consider how assessing and responding to motivation could enhance learning. © Blackwell Publishing Ltd 2011.

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

Diehl, Alexander D.; Meehan, Terrence F.; Bradford, Yvonne M.

Background: The Cell Ontology (CL) is an OBO Foundry candidate ontology covering the domain of canonical, natural biological cell types. Since its inception in 2005, the CL has undergone multiple rounds of revision and expansion, most notably in its representation of hematopoietic cells. For in vivo cells, the CL focuses on vertebrates but provides general classes that can be used for other metazoans, which can be subtyped in species-specific ontologies. Construction and content: Recent work on the CL has focused on extending the representation of various cell types, and developing new modules in the CL itself, and in related ontologiesmore » in coordination with the CL. For example, the Kidney and Urinary Pathway Ontology was used as a template to populate the CL with additional cell types. In addition, subtypes of the class 'cell in vitro' have received improved definitions and labels to provide for modularity with the representation of cells in the Cell Line Ontology and Reagent Ontology. Recent changes in the ontology development methodology for CL include a switch from OBO to OWL for the primary encoding of the ontology, and an increasing reliance on logical definitions for improved reasoning. Utility and discussion: The CL is now mandated as a metadata standard for large functional genomics and transcriptomics projects, and is used extensively for annotation, querying, and analyses of cell type specific data in sequencing consortia such as FANTOM5 and ENCODE, as well as for the NIAID ImmPort database and the Cell Image Library. The CL is also a vital component used in the modular construction of other biomedical ontologies-for example, the Gene Ontology and the cross-species anatomy ontology, Uberon, use CL to support the consistent representation of cell types across different levels of anatomical granularity, such as tissues and organs. Conclusions: The ongoing improvements to the CL make it a valuable resource to both the OBO Foundry community and the wider scientific community, and we continue to experience increased interest in the CL both among developers and within the user community.« less

G-DOC Plus - an integrative bioinformatics platform for precision medicine.

PubMed

Bhuvaneshwar, Krithika; Belouali, Anas; Singh, Varun; Johnson, Robert M; Song, Lei; Alaoui, Adil; Harris, Michael A; Clarke, Robert; Weiner, Louis M; Gusev, Yuriy; Madhavan, Subha

2016-04-30

G-DOC Plus is a data integration and bioinformatics platform that uses cloud computing and other advanced computational tools to handle a variety of biomedical BIG DATA including gene expression arrays, NGS and medical images so that they can be analyzed in the full context of other omics and clinical information. G-DOC Plus currently holds data from over 10,000 patients selected from private and public resources including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the recently added datasets from REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT), caArray studies of lung and colon cancer, ImmPort and the 1000 genomes data sets. The system allows researchers to explore clinical-omic data one sample at a time, as a cohort of samples; or at the level of population, providing the user with a comprehensive view of the data. G-DOC Plus tools have been leveraged in cancer and non-cancer studies for hypothesis generation and validation; biomarker discovery and multi-omics analysis, to explore somatic mutations and cancer MRI images; as well as for training and graduate education in bioinformatics, data and computational sciences. Several of these use cases are described in this paper to demonstrate its multifaceted usability. G-DOC Plus can be used to support a variety of user groups in multiple domains to enable hypothesis generation for precision medicine research. The long-term vision of G-DOC Plus is to extend this translational bioinformatics platform to stay current with emerging omics technologies and analysis methods to continue supporting novel hypothesis generation, analysis and validation for integrative biomedical research. By integrating several aspects of the disease and exposing various data elements, such as outpatient lab workup, pathology, radiology, current treatments, molecular signatures and expected outcomes over a web interface, G-DOC Plus will continue to strengthen precision medicine research. G-DOC Plus is available at: https://gdoc.georgetown.edu .

The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability.

PubMed

Diehl, Alexander D; Meehan, Terrence F; Bradford, Yvonne M; Brush, Matthew H; Dahdul, Wasila M; Dougall, David S; He, Yongqun; Osumi-Sutherland, David; Ruttenberg, Alan; Sarntivijai, Sirarat; Van Slyke, Ceri E; Vasilevsky, Nicole A; Haendel, Melissa A; Blake, Judith A; Mungall, Christopher J

2016-07-04

The Cell Ontology (CL) is an OBO Foundry candidate ontology covering the domain of canonical, natural biological cell types. Since its inception in 2005, the CL has undergone multiple rounds of revision and expansion, most notably in its representation of hematopoietic cells. For in vivo cells, the CL focuses on vertebrates but provides general classes that can be used for other metazoans, which can be subtyped in species-specific ontologies. Recent work on the CL has focused on extending the representation of various cell types, and developing new modules in the CL itself, and in related ontologies in coordination with the CL. For example, the Kidney and Urinary Pathway Ontology was used as a template to populate the CL with additional cell types. In addition, subtypes of the class 'cell in vitro' have received improved definitions and labels to provide for modularity with the representation of cells in the Cell Line Ontology and Reagent Ontology. Recent changes in the ontology development methodology for CL include a switch from OBO to OWL for the primary encoding of the ontology, and an increasing reliance on logical definitions for improved reasoning. The CL is now mandated as a metadata standard for large functional genomics and transcriptomics projects, and is used extensively for annotation, querying, and analyses of cell type specific data in sequencing consortia such as FANTOM5 and ENCODE, as well as for the NIAID ImmPort database and the Cell Image Library. The CL is also a vital component used in the modular construction of other biomedical ontologies-for example, the Gene Ontology and the cross-species anatomy ontology, Uberon, use CL to support the consistent representation of cell types across different levels of anatomical granularity, such as tissues and organs. The ongoing improvements to the CL make it a valuable resource to both the OBO Foundry community and the wider scientific community, and we continue to experience increased interest in the CL both among developers and within the user community.

The center for expanded data annotation and retrieval

PubMed Central

Bean, Carol A; Cheung, Kei-Hoi; Dumontier, Michel; Durante, Kim A; Gevaert, Olivier; Gonzalez-Beltran, Alejandra; Khatri, Purvesh; Kleinstein, Steven H; O’Connor, Martin J; Pouliot, Yannick; Rocca-Serra, Philippe; Sansone, Susanna-Assunta; Wiser, Jeffrey A

2015-01-01

The Center for Expanded Data Annotation and Retrieval is studying the creation of comprehensive and expressive metadata for biomedical datasets to facilitate data discovery, data interpretation, and data reuse. We take advantage of emerging community-based standard templates for describing different kinds of biomedical datasets, and we investigate the use of computational techniques to help investigators to assemble templates and to fill in their values. We are creating a repository of metadata from which we plan to identify metadata patterns that will drive predictive data entry when filling in metadata templates. The metadata repository not only will capture annotations specified when experimental datasets are initially created, but also will incorporate links to the published literature, including secondary analyses and possible refinements or retractions of experimental interpretations. By working initially with the Human Immunology Project Consortium and the developers of the ImmPort data repository, we are developing and evaluating an end-to-end solution to the problems of metadata authoring and management that will generalize to other data-management environments. PMID:26112029

Agonist Met antibodies define the signalling threshold required for a full mitogenic and invasive program of Kaposi's Sarcoma cells.

PubMed

Bardelli, Claudio; Sala, Marilena; Cavallazzi, Umberto; Prat, Maria

2005-09-09

We previously showed that the Kaposi Sarcoma line KS-IMM express a functional Met tyrosine kinase receptor, which, upon HGF stimulation, activates motogenic, proliferative, and invasive responses. In this study, we investigated the signalling pathways activated by HGF, as well as by Met monoclonal antibodies (Mabs), acting as full or partial agonists. The full agonist Mab mimics HGF in all biological and biochemical aspects. It elicits the whole spectrum of responses, while the partial agonist Mab induces only wound healing. These differences correlated with a more prolonged and sustained tyrosine phosphorylation of the receptor and MAPK evoked by HGF and by the full agonist Mab, relative to the partial agonist Mab. Since Gab1, JNK and PI 3-kinase are activated with same intensity and kinetics by HGF and by the two agonist antibodies, it is concluded that level and duration of MAPK activation by Met receptor are crucial for the induction of a full HGF-dependent mitogenic and invasive program in KS cells.

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis.

PubMed

Castillo, Ana F; Orlando, Ulises; Helfenberger, Katia E; Poderoso, Cecilia; Podesta, Ernesto J

2015-06-15

The steroidogenic acute regulatory (StAR) protein regulates the rate-limiting step in steroidogenesis, i.e. the delivery of cholesterol from the outer (OMM) to the inner (IMM) mitochondrial membrane. StAR is a 37-kDa protein with an N-terminal mitochondrial targeting sequence that is cleaved off during mitochondrial import to yield 30-kDa intramitochondrial StAR. StAR acts exclusively on the OMM and its activity is proportional to how long it remains on the OMM. However, the precise fashion and the molecular mechanism in which StAR remains on the OMM have not been elucidated yet. In this work we will discuss the role of mitochondrial fusion and StAR phosphorylation by the extracellular signal-regulated kinases 1/2 (ERK1/2) as part of the mechanism that regulates StAR retention on the OMM and activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression.

PubMed

Jung, Suna; Han, Miae; Korm, Sovannarith; Lee, Se-In; Noh, Solhee; Phorl, Sophors; Naskar, Rema; Lee, Kye-Sung; Kim, Geon-Hee; Choi, Yun-Jaie; Lee, Joo Yong

2018-06-08

Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). UCP1 increases the conductance of the inner mitochondrial membrane (IMM) for protons to make BAT mitochondria generate heat rather than ATP. HDAC6 is a cytosolic deacetylase for non-histone substrates to regulate various cellular processes, including mitochondrial quality control and dynamics. Here, we showed that the body temperature of HDAC6 knockout mice is slightly decreased in normal hosing condition. Interestingly, UCP1 was downregulated in BAT of HDAC6 knockout mice, which extensively linked mitochondrial thermogenesis. Mechanistically, we showed that cAMP-PKA signaling plays a key role in HDAC6-dependent UCP1 expression. Notably, the size of brown adipocytes and lipid droplets in HDAC6 knockout BAT is increased. Taken together, our findings suggested that HDAC6 contributes to mitochondrial thermogenesis in BAT by increasing UCP1 expression through cAMP-PKA signaling pathway. Copyright © 2018. Published by Elsevier Inc.

Pressure-Induced Polymorphic, Optical, and Electronic Transitions of Formamidinium Lead Iodide Perovskite

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

Wang, Pan; Guan, Jiwen; Galeschuk, Draven T. K.

2017-04-28

Formamidinium lead iodide (FAPbI3) perovskite as a superior solar cell material was investigated in two polymorphs at high pressures using in situ synchrotron X-ray diffraction, FTIR spectroscopy, photoluminescence (PL) spectroscopy, electrical conductivity (EC) measurements, and ab initio calculations. We identified two new structures (i.e., Imm2 and Immm) for α-FAPbI3 but only a structural distortion (in C2/c) for δ-FAPbI3 upon compression. A pressure-enhanced hydrogen bond plays a prominent role in structural modifications, as corroborated by FTIR spectroscopy. PL measurements and calculations consistently show the structure and pressure dependences of the band gap energies. Finally, EC measurements reveal drastically different transport propertiesmore » of α- and δ-FAPbI3 at low pressures but a common trend to metallic states at high pressures. All of these observations suggest strongly contrasting structural stabilities and pressure-tuned optoelectric properties of the two FAPbI3 polymorphs.« less

Relative efficiency of joint-model and full-conditional-specification multiple imputation when conditional models are compatible: The general location model.

PubMed

Seaman, Shaun R; Hughes, Rachael A

2018-06-01

Estimating the parameters of a regression model of interest is complicated by missing data on the variables in that model. Multiple imputation is commonly used to handle these missing data. Joint model multiple imputation and full-conditional specification multiple imputation are known to yield imputed data with the same asymptotic distribution when the conditional models of full-conditional specification are compatible with that joint model. We show that this asymptotic equivalence of imputation distributions does not imply that joint model multiple imputation and full-conditional specification multiple imputation will also yield asymptotically equally efficient inference about the parameters of the model of interest, nor that they will be equally robust to misspecification of the joint model. When the conditional models used by full-conditional specification multiple imputation are linear, logistic and multinomial regressions, these are compatible with a restricted general location joint model. We show that multiple imputation using the restricted general location joint model can be substantially more asymptotically efficient than full-conditional specification multiple imputation, but this typically requires very strong associations between variables. When associations are weaker, the efficiency gain is small. Moreover, full-conditional specification multiple imputation is shown to be potentially much more robust than joint model multiple imputation using the restricted general location model to mispecification of that model when there is substantial missingness in the outcome variable.

Definition of the upper reference limit for thyroglobulin antibodies according to the National Academy of Clinical Biochemistry guidelines: comparison of eleven different automated methods.

PubMed

D'Aurizio, F; Metus, P; Ferrari, A; Caruso, B; Castello, R; Villalta, D; Steffan, A; Gaspardo, K; Pesente, F; Bizzaro, N; Tonutti, E; Valverde, S; Cosma, C; Plebani, M; Tozzoli, R

2017-12-01

In the last two decades, thyroglobulin autoantibodies (TgAb) measurement has progressively switched from marker of thyroid autoimmunity to test associated with thyroglobulin (Tg) to verify the presence or absence of TgAb interference in the follow-up of patients with differentiated thyroid cancer. Of note, TgAb measurement is cumbersome: despite standardization against the International Reference Preparation MRC 65/93, several studies demonstrated high inter-method variability and wide variation in limits of detection and in reference intervals. Taking into account the above considerations, the main aim of the present study was the determination of TgAb upper reference limit (URL), according to the National Academy of Clinical Biochemistry guidelines, through the comparison of eleven commercial automated immunoassay platforms. The sera of 120 healthy males, selected from a population survey in the province of Verona, Italy, were tested for TgAb concentration using eleven IMA applied on as many automated analyzers: AIA-2000 (AIA) and AIA-CL2400 (CL2), Tosoh Bioscience; Architect (ARC), Abbott Diagnostics; Advia Centaur XP (CEN) and Immulite 2000 XPi (IMM), Siemens Healthineers; Cobas 6000 (COB), Roche Diagnostics; Kryptor (KRY), Thermo Fisher Scientific BRAHMS, Liaison XL (LIA), Diasorin; Lumipulse G (LUM), Fujirebio; Maglumi 2000 Plus (MAG), Snibe and Phadia 250 (PHA), Phadia AB, Thermo Fisher Scientific. All assays were performed according to manufacturers' instructions in six different laboratories in Friuli-Venezia Giulia and Veneto regions of Italy [Lab 1 (AIA), Lab 2 (CL2), Lab 3 (ARC, COB and LUM), Lab 4 (CEN, IMM, KRY and MAG), Lab 5 (LIA) and Lab 6 (PHA)]. Since TgAb values were not normally distributed, the experimental URL (e-URL) was established at 97.5 percentile according to the non-parametric method. TgAb e-URLs showed a significant inter-method variability. Considering the same method, e-URL was much lower than that suggested by manufacturers (m-URL), except for ARC and MAG. Correlation and linear regression were unsatisfactory. Consequently, the agreement between methods was poor, with significant bias in Bland-Altman plot. Despite the efforts for harmonization, TgAb methods cannot be used interchangeably. Therefore, additional effort is required to improve analytical performance taking into consideration approved protocols and guidelines. Moreover, TgAb URL should be used with caution in the management of differentiated thyroid carcinoma patients since the presence and/or the degree of TgAb interference in Tg measurement has not yet been well defined.

A detailed characterization of the Saharan dust collected during the Fennec campaign in 2011: in situ ground-based and laboratory measurements

NASA Astrophysics Data System (ADS)

Rocha-Lima, Adriana; Vanderlei Martins, J.; Remer, Lorraine A.; Todd, Martin; Marsham, John H.; Engelstaedter, Sebastian; Ryder, Claire L.; Cavazos-Guerra, Carolina; Artaxo, Paulo; Colarco, Peter; Washington, Richard

2018-01-01

Millions of tons of mineral dust are lifted by the wind from arid surfaces and transported around the globe every year. The physical and chemical properties of the mineral dust are needed to better constrain remote sensing observations and are of fundamental importance for the understanding of dust atmospheric processes. Ground-based in situ measurements and in situ filter collection of Saharan dust were obtained during the Fennec campaign in the central Sahara in 2011. This paper presents results of the absorption and scattering coefficients, and hence single scattering albedo (SSA), of the Saharan dust measured in real time during the last period of the campaign and subsequent laboratory analysis of the dust samples collected in two supersites, SS1 and SS2, in Algeria and in Mauritania, respectively. The samples were taken to the laboratory, where their size and aspect ratio distributions, mean chemical composition, spectral mass absorption efficiency, and spectral imaginary refractive index were obtained from the ultraviolet (UV) to the near-infrared (NIR) wavelengths. At SS1 in Algeria, the time series of the scattering coefficients during the period of the campaign show dust events exceeding 3500 Mm-1, and a relatively high mean SSA of 0.995 at 670 nm was observed at this site. The laboratory results show for the fine particle size distributions (particles diameter  < 5µm and mode diameter at 2-3 µm) in both sites a spectral dependence of the imaginary part of the refractive index Im(m) with a bow-like shape, with increased absorption in UV as well as in the shortwave infrared. The same signature was not observed, however, in the mixed particle size distribution (particle diameter < 10 µm and mode diameter at 4 µm) in Algeria. Im(m) was found to range from 0.011 to 0.001i for dust collected in Algeria and 0.008 to 0.002i for dust collected in Mauritania over the wavelength range of 350-2500 nm. Differences in the mean elemental composition of the dust collected in the supersites in Algeria and in Mauritania and between fine and mixed particle size distributions were observed from EDXRF measurements, although those differences cannot be used to explain the optical properties variability between the samples. Finally, particles with low-density typically larger than 10 µm in diameter were found in some of the samples collected at the supersite in Mauritania, but these low-density particles were not observed in Algeria.

Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells

PubMed Central

Lee, Jinwoo; Tong, Tiegang; Duan, Haichuan; Foong, Yee Hoon; Musaitif, Ibrahim; Yamazaki, Takeshi; Jefcoate, Colin

2016-01-01

The cholesterol transfer function of steroidogenic acute regulatory protein (StAR) is uniquely integrated into adrenal cells, with mRNA translation and protein kinase A (PKA) phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol-binding domain (CBD) initiates mitochondrial intermembrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here, we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells, and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extramitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion, and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: salt-inducible kinase 1 (SIK1) and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb StAR mRNA molecules via dual hybridization at the 3′- and 5′-ends and reveals an unexpectedly high frequency of 1:1 pairing with mitochondria marked by the matrix StAR protein. This pairing may be central to translation-coupled cholesterol transfer. Altogether, our results show that adrenal cells exhibit high-efficiency StAR activity that needs to integrate rapid cholesterol transfer with homeostasis and pulsatile hormonal stimulation. StAR NBD, the extended 3.5-kb mRNA, SIK1, and Tis11b play important roles. PMID:27531991

Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells.

PubMed

Lee, Jinwoo; Tong, Tiegang; Duan, Haichuan; Foong, Yee Hoon; Musaitif, Ibrahim; Yamazaki, Takeshi; Jefcoate, Colin

2016-01-01

The cholesterol transfer function of steroidogenic acute regulatory protein (StAR) is uniquely integrated into adrenal cells, with mRNA translation and protein kinase A (PKA) phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol-binding domain (CBD) initiates mitochondrial intermembrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here, we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells, and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extramitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion, and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: salt-inducible kinase 1 (SIK1) and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb StAR mRNA molecules via dual hybridization at the 3'- and 5'-ends and reveals an unexpectedly high frequency of 1:1 pairing with mitochondria marked by the matrix StAR protein. This pairing may be central to translation-coupled cholesterol transfer. Altogether, our results show that adrenal cells exhibit high-efficiency StAR activity that needs to integrate rapid cholesterol transfer with homeostasis and pulsatile hormonal stimulation. StAR NBD, the extended 3.5-kb mRNA, SIK1, and Tis11b play important roles.

Application of multiple modelling to hyperthermia estimation: reducing the effects of model mismatch.

PubMed

Potocki, J K; Tharp, H S

1993-01-01

Multiple model estimation is a viable technique for dealing with the spatial perfusion model mismatch associated with hyperthermia dosimetry. Using multiple models, spatial discrimination can be obtained without increasing the number of unknown perfusion zones. Two multiple model estimators based on the extended Kalman filter (EKF) are designed and compared with two EKFs based on single models having greater perfusion zone segmentation. Results given here indicate that multiple modelling is advantageous when the number of thermal sensors is insufficient for convergence of single model estimators having greater perfusion zone segmentation. In situations where sufficient measured outputs exist for greater unknown perfusion parameter estimation, the multiple model estimators and the single model estimators yield equivalent results.

Native Tandem and Ion Mobility Mass Spectrometry Highlight Structural and Modular Similarities in Clustered-Regularly-Interspaced Shot-Palindromic-Repeats (CRISPR)-associated Protein Complexes From Escherichia coli and Pseudomonas aeruginosa*

PubMed Central

van Duijn, Esther; Barbu, Ioana M.; Barendregt, Arjan; Jore, Matthijs M.; Wiedenheft, Blake; Lundgren, Magnus; Westra, Edze R.; Brouns, Stan J. J.; Doudna, Jennifer A.; van der Oost, John; Heck, Albert J. R.

2012-01-01

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) immune system of bacteria and archaea provides acquired resistance against viruses and plasmids, by a strategy analogous to RNA-interference. Key components of the defense system are ribonucleoprotein complexes, the composition of which appears highly variable in different CRISPR/Cas subtypes. Previous studies combined mass spectrometry, electron microscopy, and small angle x-ray scattering to demonstrate that the E. coli Cascade complex (405 kDa) and the P. aeruginosa Csy-complex (350 kDa) are similar in that they share a central spiral-shaped hexameric structure, flanked by associating proteins and one CRISPR RNA. Recently, a cryo-electron microscopy structure of Cascade revealed that the CRISPR RNA molecule resides in a groove of the hexameric backbone. For both complexes we here describe the use of native mass spectrometry in combination with ion mobility mass spectrometry to assign a stable core surrounded by more loosely associated modules. Via computational modeling subcomplex structures were proposed that relate to the experimental IMMS data. Despite the absence of obvious sequence homology between several subunits, detailed analysis of sub-complexes strongly suggests analogy between subunits of the two complexes. Probing the specific association of E. coli Cascade/crRNA to its complementary DNA target reveals a conformational change. All together these findings provide relevant new information about the potential assembly process of the two CRISPR-associated complexes. PMID:22918228

Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

NASA Astrophysics Data System (ADS)

Zhou, Mowei; Yan, Jing; Romano, Christine A.; Tebo, Bradley M.; Wysocki, Vicki H.; Paša-Tolić, Ljiljana

2018-01-01

Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase, Mnx, from Bacillus sp. PL-12 has been successfully overexpressed in active form as a protein complex with a molecular mass of 211 kDa. We have recently used surface induced dissociation (SID) and ion mobility-mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data from the native mass spectrometry experiments led to a plausible structural model of this multicopper oxidase, which has been difficult to study by conventional structural biology methods. It was also revealed that each Mnx subunit binds a variable number of copper ions. Becasue of the heterogeneity of the protein and limited mass resolution, ambiguities in assigning some of the observed peaks remained as a barrier to fully understanding the role of metals and potential unknown ligands in Mnx. In this study, we performed SID in a modified Fourier transform-ion cyclotron resonance (FTICR) mass spectrometer. The high mass accuracy and resolution offered by FTICR unveiled unexpected artificial modifications on the protein that had been previously thought to be iron bound species based on lower resolution spectra. Additionally, isotopically resolved spectra of the released subcomplexes revealed the metal binding stoichiometry at different structural levels. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes. [Figure not available: see fulltext.

DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κB p50 Transcription Factor.

PubMed

Vonderach, Matthias; Byrne, Dominic P; Barran, Perdita E; Eyers, Patrick A; Eyers, Claire E

2018-06-05

The NF-κB transcription factors are known to be extensively phosphorylated, with dynamic site-specific modification regulating their ability to dimerize and interact with DNA. p50, the proteolytic product of p105 (NF-κB1), forms homodimers that bind DNA but lack intrinsic transactivation function, functioning as repressors of transcription from κB promoters. Here, we examine the roles of specific phosphorylation events catalysed by either protein kinase A (PKA c ) or Chk1, in regulating the functions of p50 homodimers. LC-MS/MS analysis of proteolysed p50 following in vitro phosphorylation allows us to define Ser328 and Ser337 as PKA c - and Chk1-mediated modifications, and pinpoint an additional four Chk1 phosphosites: Ser65, Thr152, Ser242 and Ser248. Native mass spectrometry (MS) reveals Chk1- and PKA c -regulated disruption of p50 homodimer formation through Ser337. Additionally, we characterise the Chk1-mediated phosphosite, Ser242, as a regulator of DNA binding, with a S242D p50 phosphomimetic exhibiting a > 10-fold reduction in DNA binding affinity. Conformational dynamics of phosphomimetic p50 variants, including S242D, are further explored using ion-mobility MS (IM-MS). Finally, comparative theoretical modelling with experimentally observed p50 conformers, in the absence and presence of DNA, reveals that the p50 homodimer undergoes conformational contraction during electrospray ionisation that is stabilised by complex formation with κB DNA. Graphical Abstract ᅟ.

Modeling the interaction Between Ethylene Diamine and Water Films on the Surface of a Carbon Nanotube

NASA Technical Reports Server (NTRS)

Jaffe, Richard L.; Walther, Jens H.; Zimmerli, Urs; Koumoutsakos, Petros

2004-01-01

It has been observed that a carbon nanotube (CNT) AFM tip coated with ethylene diamine (EDA) penetrates the liquid water-air interface more easily than an uncoated nanotube tip. The EDA coating remains intact through repeated cycles of dipping and removal. In order to understand the physical basis for this observation, we use ab initio quantum chemistry calculations to study the EDA-CNT-water interaction and to parameterize a force field describing this system. Molecular dynamics (MD) simulations are carried out for EDA-water mixtures and an EDA-coated carbon nanotube immmed in water. These simulations are similar to our earlier MD study that characterized the CNT-water interface. The attractive CNT-EDA and CNT-water interactions arise primarily from van der Waals forces, and the EDA-EDA, EDA-water and water-water interactions are mainly due to hydrogen bond formation. The binding energ of single EDA molecule to the nanotube is nearly three times larger than the corresponding value found for water (4.3 versus 1.5 kcal mol, respectively). The EDA molecules readily stick to and diffuse along the CNT surface. As a resulf mixing of the EDA and water films does not occur on the timescale of the MD simulations. The EDA film reduces the hydrophobicity of the nanotube surface and acts like a prototypical surfactant in stabilizing the suspension of carbon nanotubes in water. For this presentation, we use the MD simulations to determine how the presence of the carbon nanotube surface perturbs the properties of EDA-water mixtures.

A Bayesian Poisson-lognormal Model for Count Data for Multiple-Trait Multiple-Environment Genomic-Enabled Prediction

PubMed Central

Montesinos-López, Osval A.; Montesinos-López, Abelardo; Crossa, José; Toledo, Fernando H.; Montesinos-López, José C.; Singh, Pawan; Juliana, Philomin; Salinas-Ruiz, Josafhat

2017-01-01

When a plant scientist wishes to make genomic-enabled predictions of multiple traits measured in multiple individuals in multiple environments, the most common strategy for performing the analysis is to use a single trait at a time taking into account genotype × environment interaction (G × E), because there is a lack of comprehensive models that simultaneously take into account the correlated counting traits and G × E. For this reason, in this study we propose a multiple-trait and multiple-environment model for count data. The proposed model was developed under the Bayesian paradigm for which we developed a Markov Chain Monte Carlo (MCMC) with noninformative priors. This allows obtaining all required full conditional distributions of the parameters leading to an exact Gibbs sampler for the posterior distribution. Our model was tested with simulated data and a real data set. Results show that the proposed multi-trait, multi-environment model is an attractive alternative for modeling multiple count traits measured in multiple environments. PMID:28364037

A Bayesian Poisson-lognormal Model for Count Data for Multiple-Trait Multiple-Environment Genomic-Enabled Prediction.

PubMed

Montesinos-López, Osval A; Montesinos-López, Abelardo; Crossa, José; Toledo, Fernando H; Montesinos-López, José C; Singh, Pawan; Juliana, Philomin; Salinas-Ruiz, Josafhat

2017-05-05

When a plant scientist wishes to make genomic-enabled predictions of multiple traits measured in multiple individuals in multiple environments, the most common strategy for performing the analysis is to use a single trait at a time taking into account genotype × environment interaction (G × E), because there is a lack of comprehensive models that simultaneously take into account the correlated counting traits and G × E. For this reason, in this study we propose a multiple-trait and multiple-environment model for count data. The proposed model was developed under the Bayesian paradigm for which we developed a Markov Chain Monte Carlo (MCMC) with noninformative priors. This allows obtaining all required full conditional distributions of the parameters leading to an exact Gibbs sampler for the posterior distribution. Our model was tested with simulated data and a real data set. Results show that the proposed multi-trait, multi-environment model is an attractive alternative for modeling multiple count traits measured in multiple environments. Copyright © 2017 Montesinos-López et al.

Modeling Polytomous Item Responses Using Simultaneously Estimated Multinomial Logistic Regression Models

ERIC Educational Resources Information Center

Anderson, Carolyn J.; Verkuilen, Jay; Peyton, Buddy L.

2010-01-01

Survey items with multiple response categories and multiple-choice test questions are ubiquitous in psychological and educational research. We illustrate the use of log-multiplicative association (LMA) models that are extensions of the well-known multinomial logistic regression model for multiple dependent outcome variables to reanalyze a set of…

The effects of social rearing on preferences formed during filial imprinting and their neural correlates.

PubMed

Town, Stephen Michael

2011-08-01

Filial imprinting was originally proposed to be an irreversible process by which a young animal forms a preference for an object experienced early in life. The present study examined the effects of experience after imprinting on the stability of preferences of domestic chicks (Gallus gallus domesticus) for an imprinting stimulus by rearing imprinted chicks socially or in isolation. Chicks reared socially or in isolation retained preferences for the imprinting stimulus; however, social rearing weakened the strength of preferences. The responses of neurons within the intermediate and medial mesopallium--a forebrain region necessary for imprinting were also recorded in socially reared and isolated chicks when presented with the visual component of the imprinting stimulus and novel object. Consistent with existing findings, neurons recorded from isolated chicks responded more strongly to the imprinting stimulus than novel object. However, social rearing diminished the disparity between responses to stimuli such that neurons recorded from socially reared chicks responded similarly to the imprinting stimulus and novel object. These findings suggest that social rearing may impair the retention of preferences formed during imprinting through mechanisms involving the IMM.

Plant extracts as potential mosquito larvicides

PubMed Central

Ghosh, Anupam; Chowdhury, Nandita; Chandra, Goutam

2012-01-01

Mosquitoes act as a vector for most of the life threatening diseases like malaria, yellow fever, dengue fever, chikungunya ferver, filariasis, encephalitis, West Nile Virus infection, etc. Under the Integrated Mosquito Management (IMM), emphasis was given on the application of alternative strategies in mosquito control. The continuous application of synthetic insecticides causes development of resistance in vector species, biological magnification of toxic substances through the food chain and adverse effects on environmental quality and non target organisms including human health. Application of active toxic agents from plant extracts as an alternative mosquito control strategy was available from ancient times. These are non-toxic, easily available at affordable prices, biodegradable and show broad-spectrum target-specific activities against different species of vector mosquitoes. In this article, the current state of knowledge on phytochemical sources and mosquitocidal activity, their mechanism of action on target population, variation of their larvicidal activity according to mosquito species, instar specificity, polarity of solvents used during extraction, nature of active ingredient and promising advances made in biological control of mosquitoes by plant derived secondary metabolites have been reviewed. PMID:22771587

Plant extracts as potential mosquito larvicides.

PubMed

Ghosh, Anupam; Chowdhury, Nandita; Chandra, Goutam

2012-05-01

Mosquitoes act as a vector for most of the life threatening diseases like malaria, yellow fever, dengue fever, chikungunya ferver, filariasis, encephalitis, West Nile Virus infection, etc. Under the Integrated Mosquito Management (IMM), emphasis was given on the application of alternative strategies in mosquito control. The continuous application of synthetic insecticides causes development of resistance in vector species, biological magnification of toxic substances through the food chain and adverse effects on environmental quality and non target organisms including human health. Application of active toxic agents from plant extracts as an alternative mosquito control strategy was available from ancient times. These are non-toxic, easily available at affordable prices, biodegradable and show broad-spectrum target-specific activities against different species of vector mosquitoes. In this article, the current state of knowledge on phytochemical sources and mosquitocidal activity, their mechanism of action on target population, variation of their larvicidal activity according to mosquito species, instar specificity, polarity of solvents used during extraction, nature of active ingredient and promising advances made in biological control of mosquitoes by plant derived secondary metabolites have been reviewed.

First-Principles Study of the Li-Mg-N-H System: Compound Structures and Hydrogen Storage Properties

NASA Astrophysics Data System (ADS)

Michel, Kyle; Ozolins, Vidvuds

2009-03-01

The Li-Mg-N-H system is studied with the addition of the Li4Mg(NH)3, MgNH, and Li4NH compounds using first-principles density-functional theory (DFT) calculations. A structure for the mixed imide Li4Mg(NH)3 is proposed, belonging to the Imm2 space group. A new structure for Li2Mg(NH)2 is given that has Pca21 symmetry; this compound has been previously reported as having Iba2 symmetry. The stability of the Li4Mg-imide is studied with respect to its decomposition reactions. The static, zero-point (ZPE), and vibrational energies of all relevant compounds belonging to this system are reported along with their predicted lowest-energy structures. Dehydrogenation reactions are presented that involve these phases and which are found to be spontaneously occurring within 400 K of room temperature. It is predicted that mixing LiH, LiNH2, and Li2Mg(NH)2 at 505 K will form Li4Mg(NH)3 with the release of 2.04 wt. % H2.

A Multiple Items EPQ/EOQ Model for a Vendor and Multiple Buyers System with Considering Continuous and Discrete Demand Simultaneously

NASA Astrophysics Data System (ADS)

Jonrinaldi; Rahman, T.; Henmaidi; Wirdianto, E.; Zhang, D. Z.

2018-03-01

This paper proposed a mathematical model for multiple items Economic Production and Order Quantity (EPQ/EOQ) with considering continuous and discrete demand simultaneously in a system consisting of a vendor and multiple buyers. This model is used to investigate the optimal production lot size of the vendor and the number of shipments policy of orders to multiple buyers. The model considers the multiple buyers’ holding cost as well as transportation cost, which minimize the total production and inventory costs of the system. The continuous demand from any other customers can be fulfilled anytime by the vendor while the discrete demand from multiple buyers can be fulfilled by the vendor using the multiple delivery policy with a number of shipments of items in the production cycle time. A mathematical model is developed to illustrate the system based on EPQ and EOQ model. Solution procedures are proposed to solve the model using a Mixed Integer Non Linear Programming (MINLP) and algorithm methods. Then, the numerical example is provided to illustrate the system and results are discussed.

Dynamical modelling of coordinated multiple robot systems

NASA Technical Reports Server (NTRS)

Hayati, Samad

1987-01-01

The state of the art in the modeling of the dynamics of coordinated multiple robot manipulators is summarized and various problems related to this subject are discussed. It is recognized that dynamics modeling is a component used in the design of controllers for multiple cooperating robots. As such, the discussion addresses some problems related to the control of multiple robots. The techniques used to date in the modeling of closed kinematic chains are summarized. Various efforts made to date for the control of coordinated multiple manipulators is summarized.

The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability

DOE PAGES

Diehl, Alexander D.; Meehan, Terrence F.; Bradford, Yvonne M.; ...

2016-07-04

Background: The Cell Ontology (CL) is an OBO Foundry candidate ontology covering the domain of canonical, natural biological cell types. Since its inception in 2005, the CL has undergone multiple rounds of revision and expansion, most notably in its representation of hematopoietic cells. For in vivo cells, the CL focuses on vertebrates but provides general classes that can be used for other metazoans, which can be subtyped in species-specific ontologies. Construction and content: Recent work on the CL has focused on extending the representation of various cell types, and developing new modules in the CL itself, and in related ontologiesmore » in coordination with the CL. For example, the Kidney and Urinary Pathway Ontology was used as a template to populate the CL with additional cell types. In addition, subtypes of the class 'cell in vitro' have received improved definitions and labels to provide for modularity with the representation of cells in the Cell Line Ontology and Reagent Ontology. Recent changes in the ontology development methodology for CL include a switch from OBO to OWL for the primary encoding of the ontology, and an increasing reliance on logical definitions for improved reasoning. Utility and discussion: The CL is now mandated as a metadata standard for large functional genomics and transcriptomics projects, and is used extensively for annotation, querying, and analyses of cell type specific data in sequencing consortia such as FANTOM5 and ENCODE, as well as for the NIAID ImmPort database and the Cell Image Library. The CL is also a vital component used in the modular construction of other biomedical ontologies-for example, the Gene Ontology and the cross-species anatomy ontology, Uberon, use CL to support the consistent representation of cell types across different levels of anatomical granularity, such as tissues and organs. Conclusions: The ongoing improvements to the CL make it a valuable resource to both the OBO Foundry community and the wider scientific community, and we continue to experience increased interest in the CL both among developers and within the user community.« less

A Technique of Fuzzy C-Mean in Multiple Linear Regression Model toward Paddy Yield

NASA Astrophysics Data System (ADS)

Syazwan Wahab, Nur; Saifullah Rusiman, Mohd; Mohamad, Mahathir; Amira Azmi, Nur; Che Him, Norziha; Ghazali Kamardan, M.; Ali, Maselan

2018-04-01

In this paper, we propose a hybrid model which is a combination of multiple linear regression model and fuzzy c-means method. This research involved a relationship between 20 variates of the top soil that are analyzed prior to planting of paddy yields at standard fertilizer rates. Data used were from the multi-location trials for rice carried out by MARDI at major paddy granary in Peninsular Malaysia during the period from 2009 to 2012. Missing observations were estimated using mean estimation techniques. The data were analyzed using multiple linear regression model and a combination of multiple linear regression model and fuzzy c-means method. Analysis of normality and multicollinearity indicate that the data is normally scattered without multicollinearity among independent variables. Analysis of fuzzy c-means cluster the yield of paddy into two clusters before the multiple linear regression model can be used. The comparison between two method indicate that the hybrid of multiple linear regression model and fuzzy c-means method outperform the multiple linear regression model with lower value of mean square error.

Nested Logit Models for Multiple-Choice Item Response Data

ERIC Educational Resources Information Center

Suh, Youngsuk; Bolt, Daniel M.

2010-01-01

Nested logit item response models for multiple-choice data are presented. Relative to previous models, the new models are suggested to provide a better approximation to multiple-choice items where the application of a solution strategy precedes consideration of response options. In practice, the models also accommodate collapsibility across all…

Report of the 4th European Zebrafish Principal Investigator Meeting.

PubMed

Lopes, Susana S; Distel, Martin; Linker, Claudia; Fior, Rita; Monteiro, Rui; Bianco, Isaac H; Portugues, Ruben; Strähle, Uwe; Saúde, Leonor

2016-12-01

The European Zebrafish Principal Investigator Meeting (EZPM) is an ideal forum for group leaders using this fantastic animal model not only to discuss science but also to strengthen their interactions, to push forward technological advances, and to define guidelines for the use of this fish in research. The city of Lisbon (Portugal) was voted by the European group leaders to be the setting for the 4th EZPM, and the organizing committee, composed by Leonor Saúde (iMM Lisboa, PT), Susana Lopes (CEDOC, PT), Michael Orger (Champalimaud Foundation, PT), Rui Oliveira (ISPA, PT), and António Jacinto (CEDOC, PT), was very enthusiastic to organize a productive event. The 4th EZPM took place from March 15 to 19 at Pavilhão do Conhecimento, a Science Museum and Educational Center winner of The Great Prize FAD of Arquitecture 1999 and The Society for Environmental Graphic Design Award 2011. Over 5 days, 135 group leaders (89 men and 46 women) coming from 19 different European countries and also from the United States, Turkey, Israel, Chile, and Singapore presented and discussed their recent research achievements. In addition to the scientific oral and poster presentations, the group leaders gathered in very lively community sessions on morphants versus mutants (chaired by Didier Stainier, Max Planck Institute for Heart and Lung Research, DE), funding issues (chaired by Uwe Strahle, KIT-ITG, DE), and gender equality (chaired by Corinne Houart, KCL, United Kingdom). One of the highlights of the 4th EZPM was the guided visit to Oceanário de Lisboa, an international award-winning place that celebrates life with a stunning display of living aquatic creatures.

Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

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

Zhou, Mowei; Yan, Jing; Romano, Christine A.

Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase Mnx from Bacillus sp. PL-12 has been successfully overexpressed in active form, unexpectedly, as a protein complex with a molecular weight of 211 kDa with no homology to known proteins in the database. We have recently used surface induced dissociation (SID) and ion mobility – mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data frommore » the native mass spectrometry experiment led to a plausible model of this unknown multicopper oxidase which has been difficult to study by conventional structural biology methods. However, because each subunit of Mnx binds copper ions as cofactor at varying ratios, there were remaining ambiguities in assigning some of the observed peaks to metal-binding species because of the sample heterogeneity and limited mass resolution. In this study, we performed SID in a modified Fourier transform – ion cyclotron resonance (FT-ICR) mass spectrometer for obtaining the ultimate resolution on the released subcomplexes of Mnx. The high mass accuracy and resolution unveiled unexpected artificial modifications in the protein that have been previously thought to be iron bound species based on lower resolution data. Additionally, most released subcomplexes were isotopically resolved for defining metal binding stoichiometry at each structural level. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes.« less

Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy.

PubMed

Arden, Jessica D; Lavik, Kari I; Rubinic, Kaitlin A; Chiaia, Nicolas; Khuder, Sadik A; Howard, Marthe J; Nestor-Kalinoski, Andrea L; Alberts, Arthur S; Eisenmann, Kathryn M

2015-11-01

The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous (mDia) family formins are Rho-directed effectors that regulate the F-actin cytoskeleton to support tumor cell motility. Historically, anti-invasion strategies focused upon mDia inhibition, whereas activation remained unexplored. The recent development of small molecules directly inhibiting or activating mDia-driven F-actin assembly that supports motility allows for exploration of their role in GBM. We used the formin inhibitor SMIFH2 and mDia agonists IMM-01/-02 and mDia2-DAD peptides, which disrupt autoinhibition, to examine the roles of mDia inactivation versus activation in GBM cell migration and invasion in vitro and in an ex vivo brain slice invasion model. Inhibiting mDia suppressed directional migration and spheroid invasion while preserving intrinsic random migration. mDia agonism abrogated both random intrinsic and directional migration and halted U87 spheroid invasion in ex vivo brain slices. Thus mDia agonism is a superior GBM anti-invasion strategy. We conclude that formin agonism impedes the most dangerous GBM component-tumor spread into surrounding healthy tissue. Formin activation impairs novel aspects of transformed cells and informs the development of anti-GBM invasion strategies. © 2015 Arden et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

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

Shipman, Galen M.

These are the slides for a presentation on programming models in HPC, at the Los Alamos National Laboratory's Parallel Computing Summer School. The following topics are covered: Flynn's Taxonomy of computer architectures; single instruction single data; single instruction multiple data; multiple instruction multiple data; address space organization; definition of Trinity (Intel Xeon-Phi is a MIMD architecture); single program multiple data; multiple program multiple data; ExMatEx workflow overview; definition of a programming model, programming languages, runtime systems; programming model and environments; MPI (Message Passing Interface); OpenMP; Kokkos (Performance Portable Thread-Parallel Programming Model); Kokkos abstractions, patterns, policies, and spaces; RAJA, a systematicmore » approach to node-level portability and tuning; overview of the Legion Programming Model; mapping tasks and data to hardware resources; interoperability: supporting task-level models; Legion S3D execution and performance details; workflow, integration of external resources into the programming model.« less

Occupancy Estimation and Modeling : Inferring Patterns and Dynamics of Species Occurrence

USGS Publications Warehouse

MacKenzie, D.I.; Nichols, J.D.; Royle, J. Andrew; Pollock, K.H.; Bailey, L.L.; Hines, J.E.

2006-01-01

This is the first book to examine the latest methods in analyzing presence/absence data surveys. Using four classes of models (single-species, single-season; single-species, multiple season; multiple-species, single-season; and multiple-species, multiple-season), the authors discuss the practical sampling situation, present a likelihood-based model enabling direct estimation of the occupancy-related parameters while allowing for imperfect detectability, and make recommendations for designing studies using these models. It provides authoritative insights into the latest in estimation modeling; discusses multiple models which lay the groundwork for future study designs; addresses critical issues of imperfect detectibility and its effects on estimation; and explores the role of probability in estimating in detail.

Multidimensional Extension of Multiple Indicators Multiple Causes Models to Detect DIF

ERIC Educational Resources Information Center

Lee, Soo; Bulut, Okan; Suh, Youngsuk

2017-01-01

A number of studies have found multiple indicators multiple causes (MIMIC) models to be an effective tool in detecting uniform differential item functioning (DIF) for individual items and item bundles. A recently developed MIMIC-interaction model is capable of detecting both uniform and nonuniform DIF in the unidimensional item response theory…

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

ERIC Educational Resources Information Center

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

Comparing Multiple-Group Multinomial Log-Linear Models for Multidimensional Skill Distributions in the General Diagnostic Model. Research Report. ETS RR-08-35

ERIC Educational Resources Information Center

Xu, Xueli; von Davier, Matthias

2008-01-01

The general diagnostic model (GDM) utilizes located latent classes for modeling a multidimensional proficiency variable. In this paper, the GDM is extended by employing a log-linear model for multiple populations that assumes constraints on parameters across multiple groups. This constrained model is compared to log-linear models that assume…

Multiple Indicator Stationary Time Series Models.

ERIC Educational Resources Information Center

Sivo, Stephen A.

2001-01-01

Discusses the propriety and practical advantages of specifying multivariate time series models in the context of structural equation modeling for time series and longitudinal panel data. For time series data, the multiple indicator model specification improves on classical time series analysis. For panel data, the multiple indicator model…

The Answering Process for Multiple-Choice Questions in Collaborative Learning: A Mathematical Learning Model Analysis

ERIC Educational Resources Information Center

Nakamura, Yasuyuki; Nishi, Shinnosuke; Muramatsu, Yuta; Yasutake, Koichi; Yamakawa, Osamu; Tagawa, Takahiro

2014-01-01

In this paper, we introduce a mathematical model for collaborative learning and the answering process for multiple-choice questions. The collaborative learning model is inspired by the Ising spin model and the model for answering multiple-choice questions is based on their difficulty level. An intensive simulation study predicts the possibility of…

Analyzing and Integrating Models of Multiple Text Comprehension

ERIC Educational Resources Information Center

List, Alexandra; Alexander, Patricia A.

2017-01-01

We introduce a special issue featuring four theoretical models of multiple text comprehension. We present a central framework for conceptualizing the four models in this special issue. Specifically, we chart the models according to how they consider learner, texts, task, and context factors in explaining multiple text comprehension. In addition,…

A Cognitive Diagnosis Model for Cognitively Based Multiple-Choice Options

ERIC Educational Resources Information Center

de la Torre, Jimmy

2009-01-01

Cognitive or skills diagnosis models are discrete latent variable models developed specifically for the purpose of identifying the presence or absence of multiple fine-grained skills. However, applications of these models typically involve dichotomous or dichotomized data, including data from multiple-choice (MC) assessments that are scored as…

Alternative Multiple Imputation Inference for Mean and Covariance Structure Modeling

ERIC Educational Resources Information Center

Lee, Taehun; Cai, Li

2012-01-01

Model-based multiple imputation has become an indispensable method in the educational and behavioral sciences. Mean and covariance structure models are often fitted to multiply imputed data sets. However, the presence of multiple random imputations complicates model fit testing, which is an important aspect of mean and covariance structure…

Will PEDF Therapy Reverse Chronic Demyelination and Prevent Axon Loss in a Murine Model of Progressive Multiple Sclerosis

DTIC Science & Technology

2015-12-01

Multiple Sclerosis ? PRINCIPAL INVESTIGATOR: David Pleasure MD CONTRACTING ORGANIZATION: University of California Davis, CA 95618 REPORT DATE...Murine Model of Progressive Multiple Sclerosis ? 5b. GRANT NUMBER W81XWH-12-1-0566 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Pleasure MD 5d...enhance central nervous system (CNS) remyelination and preserve CNS axons in mouse models of multiple sclerosis models. After determining the dosage of

Estimation of a Nonlinear Intervention Phase Trajectory for Multiple-Baseline Design Data

ERIC Educational Resources Information Center

Hembry, Ian; Bunuan, Rommel; Beretvas, S. Natasha; Ferron, John M.; Van den Noortgate, Wim

2015-01-01

A multilevel logistic model for estimating a nonlinear trajectory in a multiple-baseline design is introduced. The model is applied to data from a real multiple-baseline design study to demonstrate interpretation of relevant parameters. A simple change-in-levels (?"Levels") model and a model involving a quadratic function…

A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

ERIC Educational Resources Information Center

McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

2011-01-01

Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

Tests of multiplicative models in psychology: a case study using the unified theory of implicit attitudes, stereotypes, self-esteem, and self-concept.

PubMed

Blanton, Hart; Jaccard, James

2006-01-01

Theories that posit multiplicative relationships between variables are common in psychology. A. G. Greenwald et al. recently presented a theory that explicated relationships between group identification, group attitudes, and self-esteem. Their theory posits a multiplicative relationship between concepts when predicting a criterion variable. Greenwald et al. suggested analytic strategies to test their multiplicative model that researchers might assume are appropriate for testing multiplicative models more generally. The theory and analytic strategies of Greenwald et al. are used as a case study to show the strong measurement assumptions that underlie certain tests of multiplicative models. It is shown that the approach used by Greenwald et al. can lead to declarations of theoretical support when the theory is wrong as well as rejection of the theory when the theory is correct. A simple strategy for testing multiplicative models that makes weaker measurement assumptions than the strategy proposed by Greenwald et al. is suggested and discussed.

NACP Synthesis: Evaluating modeled carbon state and flux variables against multiple observational constraints (Invited)

NASA Astrophysics Data System (ADS)

Thornton, P. E.; Nacp Site Synthesis Participants

2010-12-01

The North American Carbon Program (NACP) synthesis effort includes an extensive intercomparison of modeled and observed ecosystem states and fluxes preformed with multiple models across multiple sites. The participating models span a range of complexity and intended application, while the participating sites cover a broad range of natural and managed ecosystems in North America, from the subtropics to arctic tundra, and coastal to interior climates. A unique characteristic of this collaborative effort is that multiple independent observations are available at all sites: fluxes are measured with the eddy covariance technique, and standard biometric and field sampling methods provide estimates of standing stock and annual production in multiple categories. In addition, multiple modeling approaches are employed to make predictions at each site, varying, for example, in the use of diagnostic vs. prognostic leaf area index. Given multiple independent observational constraints and multiple classes of model, we evaluate the internal consistency of observations at each site, and use this information to extend previously derived estimates of uncertainty in the flux observations. Model results are then compared with all available observations and models are ranked according to their consistency with each type of observation (high frequency flux measurement, carbon stock, annual production). We demonstrate a range of internal consistency across the sites, and show that some models which perform well against one observational metric perform poorly against others. We use this analysis to construct a hypothesis for combining eddy covariance, biometrics, and other standard physiological and ecological measurements which, as data collection proceeded over several years, would present an increasingly challenging target for next generation models.

A non-isotropic multiple-scale turbulence model

NASA Technical Reports Server (NTRS)

Chen, C. P.

1990-01-01

A newly developed non-isotropic multiple scale turbulence model (MS/ASM) is described for complex flow calculations. This model focuses on the direct modeling of Reynolds stresses and utilizes split-spectrum concepts for modeling multiple scale effects in turbulence. Validation studies on free shear flows, rotating flows and recirculating flows show that the current model perform significantly better than the single scale k-epsilon model. The present model is relatively inexpensive in terms of CPU time which makes it suitable for broad engineering flow applications.

The implementation of multiple intelligences based teaching model to improve mathematical problem solving ability for student of junior high school

NASA Astrophysics Data System (ADS)

Fasni, Nurli; Fatimah, Siti; Yulanda, Syerli

2017-05-01

This research aims to achieve some purposes such as: to know whether mathematical problem solving ability of students who have learned mathematics using Multiple Intelligences based teaching model is higher than the student who have learned mathematics using cooperative learning; to know the improvement of the mathematical problem solving ability of the student who have learned mathematics using Multiple Intelligences based teaching model., to know the improvement of the mathematical problem solving ability of the student who have learned mathematics using cooperative learning; to know the attitude of the students to Multiple Intelligences based teaching model. The method employed here is quasi-experiment which is controlled by pre-test and post-test. The population of this research is all of VII grade in SMP Negeri 14 Bandung even-term 2013/2014, later on two classes of it were taken for the samples of this research. A class was taught using Multiple Intelligences based teaching model and the other one was taught using cooperative learning. The data of this research were gotten from the test in mathematical problem solving, scale questionnaire of the student attitudes, and observation. The results show the mathematical problem solving of the students who have learned mathematics using Multiple Intelligences based teaching model learning is higher than the student who have learned mathematics using cooperative learning, the mathematical problem solving ability of the student who have learned mathematics using cooperative learning and Multiple Intelligences based teaching model are in intermediate level, and the students showed the positive attitude in learning mathematics using Multiple Intelligences based teaching model. As for the recommendation for next author, Multiple Intelligences based teaching model can be tested on other subject and other ability.

MULTIVARIATE LINEAR MIXED MODELS FOR MULTIPLE OUTCOMES. (R824757)

EPA Science Inventory

We propose a multivariate linear mixed (MLMM) for the analysis of multiple outcomes, which generalizes the latent variable model of Sammel and Ryan. The proposed model assumes a flexible correlation structure among the multiple outcomes, and allows a global test of the impact of ...

A model of human decision making in multiple process monitoring situations

NASA Technical Reports Server (NTRS)

Greenstein, J. S.; Rouse, W. B.

1982-01-01

Human decision making in multiple process monitoring situations is considered. It is proposed that human decision making in many multiple process monitoring situations can be modeled in terms of the human's detection of process related events and his allocation of attention among processes once he feels event have occurred. A mathematical model of human event detection and attention allocation performance in multiple process monitoring situations is developed. An assumption made in developing the model is that, in attempting to detect events, the human generates estimates of the probabilities that events have occurred. An elementary pattern recognition technique, discriminant analysis, is used to model the human's generation of these probability estimates. The performance of the model is compared to that of four subjects in a multiple process monitoring situation requiring allocation of attention among processes.

Peak Determination of ^35 Cl(n,γ) Lines

NASA Astrophysics Data System (ADS)

Young, Patrick

2004-10-01

To achieve our goal of performing a stringent test of the Isobaric Multiplet Mass Equation (IMME) for the lowest T = 2 quintuplet, an accurate measurement of the mass of ^32 S in its lowest T = 2 state is needed, as the other masses of the members of the quintuplet are well known [1]. To achieve the desired precision, several calibration reactions are required including ^35 Cl(n,γ). A proton beam of 1.912 MeV is incident upon a Li 2 O target to create neutrons via ^7Li(p,n). The neutrons are then moderated and absorbed by a volume of NaCl. The resulting radiation is measured with a Ge(Li) detector. Due to differences in the position of the source during calibration versus data runs, a source of mis-calibration may result from detector orientation to and distance from the source [2]. We are currently measuring the centroid shifts with respect to detector angle to see its influence upon our data collection. [1] K. Blaum, G. Audi et. al, Phys. Rev. Lett., 91, 260801, (2003) [2] R. G. Helmer, R. J. Gehrke, R. C. Greenwood, Nucl. Instr. and Meth., 123 (1975) p. 51-59.

A novel four-dimensional analytical approach for analysis of complex samples.

PubMed

Stephan, Susanne; Jakob, Cornelia; Hippler, Jörg; Schmitz, Oliver J

2016-05-01

A two-dimensional LC (2D-LC) method, based on the work of Erni and Frei in 1978, was developed and coupled to an ion mobility-high-resolution mass spectrometer (IM-MS), which enabled the separation of complex samples in four dimensions (2D-LC, ion mobility spectrometry (IMS), and mass spectrometry (MS)). This approach works as a continuous multiheart-cutting LC system, using a long modulation time of 4 min, which allows the complete transfer of most of the first - dimension peaks to the second - dimension column without fractionation, in comparison to comprehensive two-dimensional liquid chromatography. Hence, each compound delivers only one peak in the second dimension, which simplifies the data handling even when ion mobility spectrometry as a third and mass spectrometry as a fourth dimension are introduced. The analysis of a plant extract from Ginkgo biloba shows the separation power of this four-dimensional separation method with a calculated total peak capacity of more than 8700. Furthermore, the advantage of ion mobility for characterizing unknown compounds by their collision cross section (CCS) and accurate mass in a non-target approach is shown for different matrices like plant extracts and coffee. Graphical abstract Principle of the four-dimensional separation.

Structural phase transitions in GaAs to 108 GPa

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

Weir, S.T.; Vohra, Y.K.; Vanderborgh, C.A.

1989-01-15

The III-V compound GaAs was studied using energy-dispersive x-ray diffraction with a synchro- tron source up to a pressure of 108 GPa. When the pressure was increased to 16.6 GPa, the GaAs sample transformed from the zinc-blende structure to an orthorhombic structure (GaAs(II)), space group Pmm2, consisting of a primitive orthorhombic lattice with a basis of (0,0,0) and (0,(1/2,..cap alpha..), where ..cap alpha.. = 0.35. Upon a further increase of pressure to 24 +- 1 GPa, GaAs(II) transformed to another orthorhombic structure (GaAs(III)), space group Imm2, consisting of a body-centered orthorhombic lattice with a basis of (0,0,0) and (0, (1/2,..delta..),more » where ..delta.. is 0.425 at 28.1 GPa. With increasing pressure, ..delta.. approached (1/2 and the GaAs(III) structure gradually assumed the symmetry of the simple hexagonal structure. The transition to the simple hexagonal structure (GaAs(IV)) was completed in the vicinity of 60--80 GPa. The structure remains simple hexagonal up to at least 108 GPa, the highest pressure reached in this study.« less

Nonlinear Electrostatic Properties of Lunar Dust

NASA Technical Reports Server (NTRS)

Irwin, Stacy A.

2012-01-01

A laboratory experiment was designed to study the induction charging and charge decay characteristics of small dielectric particles, or glass beads. Initially, the goal of the experiment was further understanding of induction charging of lunar dust particles. However, the mechanism of charging became a point of greater interest as the project continued. Within an environmentally-controlled acrylic glove box was placed a large parallel plate capacitor at high-voltage (HV) power supply with reversible polarity. Spherical 1-mm and 0.5-mm glass beads, singly, were placed between the plates, and their behaviors recorded on video and quantified. Nearly a hundred trials at various humidities were performed. The analysis of the results indicated a non-linear relationship between humidity and particle charge exchange time (CET), for both sizes of beads. Further, a difference in CET for top-resting beads and bottom-resting beads hinted at a different charging mechanism than that of simple induction. Results from the I-mm bead trials were presented at several space science and physics conferences in 2008 and 2009, and were published as a Master's thesis in August 2009. Tangential work stemming from this project resulted in presentations at other international conferences in 2010, and selection to attend workshop on granular matter flow 2011.

Laser micro-structuring of surfaces for applications in materials and biomedical science

NASA Astrophysics Data System (ADS)

Sarzyński, Antoni; Marczak, Jan; Strzelec, Marek; Rycyk, Antoni; CzyŻ, Krzysztof; Chmielewska, Danuta

2016-12-01

Laser radiation is used, among others, for surface treatment of various materials. At the Institute of Optoelectronics, under the direction of the late Professor Jan Marczak, a number of works in the field of laser materials processing were performed. Among them special recognition deserves flagship work of Professor Jan Marczak: implementation in Poland laser cleaning method of artworks. Another big project involved the direct method of laser interference lithography. These two projects have already been widely discussed in many national and international scientific conferences. They will also be discussed at SLT2016. In addition to these two projects in the Laboratory of Lasers Applications many other works have been carried out, some of which will be separately presented at the SLT2016 Conference. These included laser decorating of ceramics and glass (three projects completed in cooperation with the Institute of Ceramics and Building Materials), interference structuring medical implants (together with the Warsaw University of Technology), testing the adhesion of thin layers (project implemented together with IFTR PAS), structuring layers of DLC for growing endothelial cells (together with IMMS PAS), engraving glass for microfluidic applications, metal marking, sapphire cutting and finally the production of microsieves for separating of blood cells.

Low-lying level structure of 56Cu and its implications for the rp process

NASA Astrophysics Data System (ADS)

Ong, W.-J.; Langer, C.; Montes, F.; Aprahamian, A.; Bardayan, D. W.; Bazin, D.; Brown, B. A.; Browne, J.; Crawford, H.; Cyburt, R.; Deleeuw, E. B.; Domingo-Pardo, C.; Gade, A.; George, S.; Hosmer, P.; Keek, L.; Kontos, A.; Lee, I.-Y.; Lemasson, A.; Lunderberg, E.; Maeda, Y.; Matos, M.; Meisel, Z.; Noji, S.; Nunes, F. M.; Nystrom, A.; Perdikakis, G.; Pereira, J.; Quinn, S. J.; Recchia, F.; Schatz, H.; Scott, M.; Siegl, K.; Simon, A.; Smith, M.; Spyrou, A.; Stevens, J.; Stroberg, S. R.; Weisshaar, D.; Wheeler, J.; Wimmer, K.; Zegers, R. G. T.

2017-05-01

The low-lying energy levels of proton-rich 56Cu have been extracted using in-beam γ -ray spectroscopy with the state-of-the-art γ -ray tracking array GRETINA in conjunction with the S800 spectrograph at the National Superconducting Cyclotron Laboratory at Michigan State University. Excited states in 56Cu serve as resonances in the 55Ni(p ,γ )56Cu reaction, which is a part of the rp process in type-I x-ray bursts. To resolve existing ambiguities in the reaction Q value, a more localized isobaric multiplet mass equation (IMME) fit is used, resulting in Q =639 ±82 keV. We derive the first experimentally constrained thermonuclear reaction rate for 55Ni(p ,γ )56Cu . We find that, with this new rate, the rp process may bypass the 56Ni waiting point via the 55Ni(p ,γ ) reaction for typical x-ray burst conditions with a branching of up to ˜40 % . We also identify additional nuclear physics uncertainties that need to be addressed before drawing final conclusions about the rp -process reaction flow in the 56Ni region.

Les conditions d’hébergement favorables au rétablissement : perspective des usagers et usagères

PubMed Central

Piat, Myra; Boyer, Richard; Cloutier, Simon; Fleury, Marie-Josée; Lesage, Alain

2016-01-01

Cette recherche vise à mieux comprendre le rôle de l’hébergement dans le rétablissement des personnes vivant avec une maladie mentale grave. Quarante résidents et résidentes de différents types d’hébergement communautaire structuré ont été interrogés sur les conditions d’hébergement qui favorisent leur rétablissement. Les résultats indiquent qu’aux yeux des résidents et résidentes, les conditions matérielles d’existence ont une influence déterminante sur le rétablissement. Leurs préoccupations s’articulent autour des besoins de base tels que l’alimentation, le coût, les commodités et la qualité de leur hébergement. Les relations sociales avec leur entourage immédiat ont également une grande influence sur le rétablissement des personnes, lesquelles souhaitent d’abord conserver leurs modestes acquis, tant matériels que sociaux. Cette stabilité est prérequise à leur rétablissement. PMID:27099410

ℓ(p)-Norm multikernel learning approach for stock market price forecasting.

PubMed

Shao, Xigao; Wu, Kun; Liao, Bifeng

2012-01-01

Linear multiple kernel learning model has been used for predicting financial time series. However, ℓ(1)-norm multiple support vector regression is rarely observed to outperform trivial baselines in practical applications. To allow for robust kernel mixtures that generalize well, we adopt ℓ(p)-norm multiple kernel support vector regression (1 ≤ p < ∞) as a stock price prediction model. The optimization problem is decomposed into smaller subproblems, and the interleaved optimization strategy is employed to solve the regression model. The model is evaluated on forecasting the daily stock closing prices of Shanghai Stock Index in China. Experimental results show that our proposed model performs better than ℓ(1)-norm multiple support vector regression model.

[Model of multiple seasonal autoregressive integrated moving average model and its application in prediction of the hand-foot-mouth disease incidence in Changsha].

PubMed

Tan, Ting; Chen, Lizhang; Liu, Fuqiang

2014-11-01

To establish multiple seasonal autoregressive integrated moving average model (ARIMA) according to the hand-foot-mouth disease incidence in Changsha, and to explore the feasibility of the multiple seasonal ARIMA in predicting the hand-foot-mouth disease incidence. EVIEWS 6.0 was used to establish multiple seasonal ARIMA according to the hand-foot- mouth disease incidence from May 2008 to August 2013 in Changsha, and the data of the hand- foot-mouth disease incidence from September 2013 to February 2014 were served as the examined samples of the multiple seasonal ARIMA, then the errors were compared between the forecasted incidence and the real value. Finally, the incidence of hand-foot-mouth disease from March 2014 to August 2014 was predicted by the model. After the data sequence was handled by smooth sequence, model identification and model diagnosis, the multiple seasonal ARIMA (1, 0, 1)×(0, 1, 1)12 was established. The R2 value of the model fitting degree was 0.81, the root mean square prediction error was 8.29 and the mean absolute error was 5.83. The multiple seasonal ARIMA is a good prediction model, and the fitting degree is good. It can provide reference for the prevention and control work in hand-foot-mouth disease.

Improvements in simulation of multiple scattering effects in ATLAS fast simulation

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

Basalaev, A. E., E-mail: artem.basalaev@cern.ch

Fast ATLAS Tracking Simulation (Fatras) package was verified on single layer geometry with respect to full simulation with GEANT4. Fatras hadronic interactions and multiple scattering simulation were studied in comparison with GEANT4. Disagreement was found in multiple scattering distributions of primary charged particles (μ, π, e). A new model for multiple scattering simulation was implemented in Fatras. The model was based on R. Frühwirth’s mixture models. New model was tested on single layer geometry and a good agreement with GEANT4 was achieved. Also a comparison of reconstructed tracks’ parameters was performed for Inner Detector geometry, and Fatras with new multiplemore » scattering model proved to have better agreement with GEANT4. New model of multiple scattering was added as a part of Fatras package in the development release of ATLAS software—ATHENA.« less

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Comparing methods of analysing datasets with small clusters: case studies using four paediatric datasets.

PubMed

Marston, Louise; Peacock, Janet L; Yu, Keming; Brocklehurst, Peter; Calvert, Sandra A; Greenough, Anne; Marlow, Neil

2009-07-01

Studies of prematurely born infants contain a relatively large percentage of multiple births, so the resulting data have a hierarchical structure with small clusters of size 1, 2 or 3. Ignoring the clustering may lead to incorrect inferences. The aim of this study was to compare statistical methods which can be used to analyse such data: generalised estimating equations, multilevel models, multiple linear regression and logistic regression. Four datasets which differed in total size and in percentage of multiple births (n = 254, multiple 18%; n = 176, multiple 9%; n = 10 098, multiple 3%; n = 1585, multiple 8%) were analysed. With the continuous outcome, two-level models produced similar results in the larger dataset, while generalised least squares multilevel modelling (ML GLS 'xtreg' in Stata) and maximum likelihood multilevel modelling (ML MLE 'xtmixed' in Stata) produced divergent estimates using the smaller dataset. For the dichotomous outcome, most methods, except generalised least squares multilevel modelling (ML GH 'xtlogit' in Stata) gave similar odds ratios and 95% confidence intervals within datasets. For the continuous outcome, our results suggest using multilevel modelling. We conclude that generalised least squares multilevel modelling (ML GLS 'xtreg' in Stata) and maximum likelihood multilevel modelling (ML MLE 'xtmixed' in Stata) should be used with caution when the dataset is small. Where the outcome is dichotomous and there is a relatively large percentage of non-independent data, it is recommended that these are accounted for in analyses using logistic regression with adjusted standard errors or multilevel modelling. If, however, the dataset has a small percentage of clusters greater than size 1 (e.g. a population dataset of children where there are few multiples) there appears to be less need to adjust for clustering.

Cognitive Affective Engagement Model of Multiple Source Use

ERIC Educational Resources Information Center

List, Alexandra; Alexander, Patricia A.

2017-01-01

This article introduces the cognitive affective engagement model (CAEM) of multiple source use. The CAEM is presented as a way of unifying cognitive and behaviorally focused models of multiple text engagement with research on the role of affective factors (e.g., interest) in text processing. The CAEM proposes that students' engagement with…

Electron Injections: A Study of Electron Acceleration by Multiple Dipolarizing Flux Bundles Using an Analytical Model

NASA Astrophysics Data System (ADS)

Gabrielse, C.; Angelopoulos, V.; Artemyev, A.; Runov, A.; Harris, C.

2016-12-01

We study energetic electron injections using an analytical model that self-consistently describes electric and magnetic field perturbations of transient, localized dipolarizing flux bundles (DFBs). Previous studies using THEMIS, Van Allen Probes, and the Magnetospheric Multiscale Mission have shown that injections can occur on short (minutes) or long (10s of minutes) timescales. These studies suggest that the short timescale injections correspond to a single DFB, whereas long timescale injections are likely caused by an aggregate of multiple DFBs, each incrementally heating the particle population. We therefore model the effects of multiple DFBs on the electron population using multi-spacecraft observations of the fields and particle fluxes to constrain the model parameters. The analytical model is the first of its kind to model multiple dipolarization fronts in order to better understand the transport and acceleration process throughout the plasma sheet. It can reproduce most injection signatures at multiple locations simultaneously, reaffirming earlier findings that multiple earthward-traveling DFBs can both transport and accelerate electrons to suprathermal energies, and can thus be considered the injections' primary driver.

Experimental models of demyelination and remyelination.

PubMed

Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

2017-08-29

Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Using multiple group modeling to test moderators in meta-analysis.

PubMed

Schoemann, Alexander M

2016-12-01

Meta-analysis is a popular and flexible analysis that can be fit in many modeling frameworks. Two methods of fitting meta-analyses that are growing in popularity are structural equation modeling (SEM) and multilevel modeling (MLM). By using SEM or MLM to fit a meta-analysis researchers have access to powerful techniques associated with SEM and MLM. This paper details how to use one such technique, multiple group analysis, to test categorical moderators in meta-analysis. In a multiple group meta-analysis a model is fit to each level of the moderator simultaneously. By constraining parameters across groups any model parameter can be tested for equality. Using multiple groups to test for moderators is especially relevant in random-effects meta-analysis where both the mean and the between studies variance of the effect size may be compared across groups. A simulation study and the analysis of a real data set are used to illustrate multiple group modeling with both SEM and MLM. Issues related to multiple group meta-analysis and future directions for research are discussed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Preliminary Tsunami vulnerability analysis for Bakirkoy district in Istanbul

NASA Astrophysics Data System (ADS)

Tufekci, Duygu; Lutfi Suzen, M.; Cevdet Yalciner, Ahmet; Zaytsev, Andrey

2016-04-01

Resilience of coastal utilities after earthquakes and tsunamis has major importance for efficient and proper rescue and recovery operations soon after the disasters. Vulnerability assessment of coastal areas under extreme events has major importance for preparedness and development of mitigation strategies. The Sea of Marmara has experienced numerous earthquakes as well as associated tsunamis. There are variety of coastal facilities such as ports, small craft harbors, and terminals for maritime transportation, water front roads and business centers mainly at North Coast of Marmara Sea in megacity Istanbul. A detailed vulnerability analysis for Yenikapi region and a detailed resilience analysis for Haydarpasa port in Istanbul have been studied in previously by Cankaya et al., (2015) and Aytore et al., (2015) in SATREPS project. In this study, the methodology of vulnerability analysis under tsunami attack given in Cankaya et al., (2015) is modified and applied to Bakirkoy district of Istanbul. Bakirkoy district is located at western part of Istanbul and faces to the North Coast of Marmara Sea from 28.77oE to 28.89oE. High resolution spatial dataset of Istanbul Metropolitan Municipality (IMM) is used and analyzed. The bathymetry and topography database and the spatial dataset containing all buildings/structures/infrastructures in the district are collated and utilized for tsunami numerical modeling and following vulnerability analysis. The tsunami parameters from deterministically defined worst case scenarios are computed from the simulations using tsunami numerical model NAMI DANCE. The vulnerability assessment parameters in the district according to vulnerability and resilience are defined; and scored by implementation of a GIS based TVA with appropriate MCDA methods. The risk level is computed using tsunami intensity (level of flow depth from simulations) and TVA results at every location in Bakirkoy district. The preliminary results are presented and discussed. Acknowledgements: Partial support by Japan-Turkey Joint Research Project by JICA on earthquakes and tsunamis in Marmara Region in (JICA SATREPS - MarDiM Project), 603839 ASTARTE Project of EU, UDAP-C-12-14 project of AFAD, Turkey, 108Y227, 113M556, 213M534 projects of TUBITAK Turkey, RAPSODI (CONCERT_Dis-021) of CONCERT-Japan Joint Call and Istanbul Metropolitan Municipality are acknowledged.

ℓ p-Norm Multikernel Learning Approach for Stock Market Price Forecasting

PubMed Central

Shao, Xigao; Wu, Kun; Liao, Bifeng

2012-01-01

Linear multiple kernel learning model has been used for predicting financial time series. However, ℓ 1-norm multiple support vector regression is rarely observed to outperform trivial baselines in practical applications. To allow for robust kernel mixtures that generalize well, we adopt ℓ p-norm multiple kernel support vector regression (1 ≤ p < ∞) as a stock price prediction model. The optimization problem is decomposed into smaller subproblems, and the interleaved optimization strategy is employed to solve the regression model. The model is evaluated on forecasting the daily stock closing prices of Shanghai Stock Index in China. Experimental results show that our proposed model performs better than ℓ 1-norm multiple support vector regression model. PMID:23365561

Can job redesign interventions influence a broad range of employee outcomes by changing multiple job characteristics? A quasi-experimental study.

PubMed

Holman, David; Axtell, Carolyn

2016-07-01

Many job redesign interventions are based on a multiple mediator-multiple outcome model in which the job redesign intervention indirectly influences a broad range of employee outcomes by changing multiple job characteristics. As this model remains untested, the aim of this study is to test a multiple mediator-multiple outcome model of job redesign. Multilevel analysis of data from a quasi-experimental job redesign intervention in a call center confirmed the hypothesized model and showed that the job redesign intervention affected a broad range of employee outcomes (i.e., employee well-being, psychological contract fulfillment, and supervisor-rated job performance) through changes in 2 job characteristics (i.e., job control and feedback). The results provide further evidence for the efficacy and mechanisms of job redesign interventions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

PubMed

Kleber, Christian; Becker, Christopher A; Malysch, Tom; Reinhold, Jens M; Tsitsilonis, Serafeim; Duda, Georg N; Schmidt-Bleek, Katharina; Schaser, Klaus D

2015-07-01

Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Progression of regional grey matter atrophy in multiple sclerosis

PubMed Central

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis. PMID:29741648

Progression of regional grey matter atrophy in multiple sclerosis.

PubMed

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

Multi-objective optimization for generating a weighted multi-model ensemble

NASA Astrophysics Data System (ADS)

Lee, H.

2017-12-01

Many studies have demonstrated that multi-model ensembles generally show better skill than each ensemble member. When generating weighted multi-model ensembles, the first step is measuring the performance of individual model simulations using observations. There is a consensus on the assignment of weighting factors based on a single evaluation metric. When considering only one evaluation metric, the weighting factor for each model is proportional to a performance score or inversely proportional to an error for the model. While this conventional approach can provide appropriate combinations of multiple models, the approach confronts a big challenge when there are multiple metrics under consideration. When considering multiple evaluation metrics, it is obvious that a simple averaging of multiple performance scores or model ranks does not address the trade-off problem between conflicting metrics. So far, there seems to be no best method to generate weighted multi-model ensembles based on multiple performance metrics. The current study applies the multi-objective optimization, a mathematical process that provides a set of optimal trade-off solutions based on a range of evaluation metrics, to combining multiple performance metrics for the global climate models and their dynamically downscaled regional climate simulations over North America and generating a weighted multi-model ensemble. NASA satellite data and the Regional Climate Model Evaluation System (RCMES) software toolkit are used for assessment of the climate simulations. Overall, the performance of each model differs markedly with strong seasonal dependence. Because of the considerable variability across the climate simulations, it is important to evaluate models systematically and make future projections by assigning optimized weighting factors to the models with relatively good performance. Our results indicate that the optimally weighted multi-model ensemble always shows better performance than an arithmetic ensemble mean and may provide reliable future projections.

User's Guide and Download for IECCU- Indoor Environmental Concentrations in Buildings with Conditioned and Unconditioned Zones

EPA Pesticide Factsheets

This program serves two purposes: (1) as a general-purpose indoor exposure model in buildings with multiple zones, multiple chemicals and multiple sources and sinks, and (2) as a special-purpose concentration model

Applying a Multiple Group Causal Indicator Modeling Framework to the Reading Comprehension Skills of Third, Seventh, and Tenth Grade Students

ERIC Educational Resources Information Center

Tighe, Elizabeth L.; Wagner, Richard K.; Schatschneider, Christopher

2015-01-01

This study demonstrates the utility of applying a causal indicator modeling framework to investigate important predictors of reading comprehension in third, seventh, and tenth grade students. The results indicated that a 4-factor multiple indicator multiple indicator cause (MIMIC) model of reading comprehension provided adequate fit at each grade…

Multiple-Use Site Demand Analysis: An Application to the Boundary Waters Canoe Area Wilderness.

ERIC Educational Resources Information Center

Peterson, George L.; And Others

1982-01-01

A single-site, multiple-use model for analyzing trip demand is derived from a multiple site regional model based on utility maximizing choice theory. The model is used to analyze and compare trips to the Boundary Waters Canoe Area Wilderness for several types of use. Travel cost elasticities of demand are compared and discussed. (Authors/JN)

A single predator multiple prey model with prey mutation

NASA Astrophysics Data System (ADS)

Mullan, Rory; Abernethy, Gavin M.; Glass, David H.; McCartney, Mark

2016-11-01

A multiple species predator-prey model is expanded with the introduction of a coupled map lattice for the prey, allowing the prey to mutate discretely into other prey species. The model is examined in its single predator, multiple mutating prey form. Two unimodal maps are used for the underlying dynamics of the prey species, with different predation strategies being used. Conclusions are drawn on how varying the control parameters of the model governs the overall behaviour and survival of the species. It is observed that in such a complex system, with multiple mutating prey, a large range of non-linear dynamics is possible.

Multiple imputation of covariates by fully conditional specification: Accommodating the substantive model

PubMed Central

Seaman, Shaun R; White, Ian R; Carpenter, James R

2015-01-01

Missing covariate data commonly occur in epidemiological and clinical research, and are often dealt with using multiple imputation. Imputation of partially observed covariates is complicated if the substantive model is non-linear (e.g. Cox proportional hazards model), or contains non-linear (e.g. squared) or interaction terms, and standard software implementations of multiple imputation may impute covariates from models that are incompatible with such substantive models. We show how imputation by fully conditional specification, a popular approach for performing multiple imputation, can be modified so that covariates are imputed from models which are compatible with the substantive model. We investigate through simulation the performance of this proposal, and compare it with existing approaches. Simulation results suggest our proposal gives consistent estimates for a range of common substantive models, including models which contain non-linear covariate effects or interactions, provided data are missing at random and the assumed imputation models are correctly specified and mutually compatible. Stata software implementing the approach is freely available. PMID:24525487

Adjustment of Measurements with Multiplicative Errors: Error Analysis, Estimates of the Variance of Unit Weight, and Effect on Volume Estimation from LiDAR-Type Digital Elevation Models

PubMed Central

Shi, Yun; Xu, Peiliang; Peng, Junhuan; Shi, Chuang; Liu, Jingnan

2014-01-01

Modern observation technology has verified that measurement errors can be proportional to the true values of measurements such as GPS, VLBI baselines and LiDAR. Observational models of this type are called multiplicative error models. This paper is to extend the work of Xu and Shimada published in 2000 on multiplicative error models to analytical error analysis of quantities of practical interest and estimates of the variance of unit weight. We analytically derive the variance-covariance matrices of the three least squares (LS) adjustments, the adjusted measurements and the corrections of measurements in multiplicative error models. For quality evaluation, we construct five estimators for the variance of unit weight in association of the three LS adjustment methods. Although LiDAR measurements are contaminated with multiplicative random errors, LiDAR-based digital elevation models (DEM) have been constructed as if they were of additive random errors. We will simulate a model landslide, which is assumed to be surveyed with LiDAR, and investigate the effect of LiDAR-type multiplicative error measurements on DEM construction and its effect on the estimate of landslide mass volume from the constructed DEM. PMID:24434880

Continuum mesoscopic framework for multiple interacting species and processes on multiple site types and/or crystallographic planes.

PubMed

Chatterjee, Abhijit; Vlachos, Dionisios G

2007-07-21

While recently derived continuum mesoscopic equations successfully bridge the gap between microscopic and macroscopic physics, so far they have been derived only for simple lattice models. In this paper, general deterministic continuum mesoscopic equations are derived rigorously via nonequilibrium statistical mechanics to account for multiple interacting surface species and multiple processes on multiple site types and/or different crystallographic planes. Adsorption, desorption, reaction, and surface diffusion are modeled. It is demonstrated that contrary to conventional phenomenological continuum models, microscopic physics, such as the interaction potential, determines the final form of the mesoscopic equation. Models of single component diffusion and binary diffusion of interacting particles on single-type site lattice and of single component diffusion on complex microporous materials' lattices consisting of two types of sites are derived, as illustrations of the mesoscopic framework. Simplification of the diffusion mesoscopic model illustrates the relation to phenomenological models, such as the Fickian and Maxwell-Stefan transport models. It is demonstrated that the mesoscopic equations are in good agreement with lattice kinetic Monte Carlo simulations for several prototype examples studied.

Testing the Multiple in the Multiple Read-Out Model of Visual Word Recognition

ERIC Educational Resources Information Center

De Moor, Wendy; Verguts, Tom; Brysbaert, Marc

2005-01-01

This study provided a test of the multiple criteria concept used for lexical decision, as implemented in J. Grainger and A. M. Jacobs's (1996) multiple read-out model. This account predicts more inhibition (or less facilitation) from a masked neighbor when accuracy is stressed more but more facilitation (or less inhibition) when the speed of…

Synthetic observations of protostellar multiple systems

NASA Astrophysics Data System (ADS)

Lomax, O.; Whitworth, A. P.

2018-04-01

Observations of protostars are often compared with synthetic observations of models in order to infer the underlying physical properties of the protostars. The majority of these models have a single protostar, attended by a disc and an envelope. However, observational and numerical evidence suggests that a large fraction of protostars form as multiple systems. This means that fitting models of single protostars to observations may be inappropriate. We produce synthetic observations of protostellar multiple systems undergoing realistic, non-continuous accretion. These systems consist of multiple protostars with episodic luminosities, embedded self-consistently in discs and envelopes. We model the gas dynamics of these systems using smoothed particle hydrodynamics and we generate synthetic observations by post-processing the snapshots using the SPAMCART Monte Carlo radiative transfer code. We present simulation results of three model protostellar multiple systems. For each of these, we generate 4 × 104 synthetic spectra at different points in time and from different viewing angles. We propose a Bayesian method, using similar calculations to those presented here, but in greater numbers, to infer the physical properties of protostellar multiple systems from observations.

Predicting Upwelling Radiance on the West Florida Shelf

DTIC Science & Technology

2006-03-31

National Science Foundation . The chemical and biological model includes the ability to simulate multiple groups of phytoplankton, multiple limiting nutrients, spectral light harvesting by phytoplankton, multiple particulate and dissolved degradational pools of organic material, and non-stoichometric carbon, nitrogen, phosphorus, silica, and iron dynamics. It also includes a complete spectral light model for the prediction of Inherent Optical Properties (IOPs). The coupling of the predicted IOP model (Ecosim 2.0) with robust radiative transfer model (Ecolight

A multiple-feature and multiple-kernel scene segmentation algorithm for humanoid robot.

PubMed

Liu, Zhi; Xu, Shuqiong; Zhang, Yun; Chen, Chun Lung Philip

2014-11-01

This technical correspondence presents a multiple-feature and multiple-kernel support vector machine (MFMK-SVM) methodology to achieve a more reliable and robust segmentation performance for humanoid robot. The pixel wise intensity, gradient, and C1 SMF features are extracted via the local homogeneity model and Gabor filter, which would be used as inputs of MFMK-SVM model. It may provide multiple features of the samples for easier implementation and efficient computation of MFMK-SVM model. A new clustering method, which is called feature validity-interval type-2 fuzzy C-means (FV-IT2FCM) clustering algorithm, is proposed by integrating a type-2 fuzzy criterion in the clustering optimization process to improve the robustness and reliability of clustering results by the iterative optimization. Furthermore, the clustering validity is employed to select the training samples for the learning of the MFMK-SVM model. The MFMK-SVM scene segmentation method is able to fully take advantage of the multiple features of scene image and the ability of multiple kernels. Experiments on the BSDS dataset and real natural scene images demonstrate the superior performance of our proposed method.

Testing Group Mean Differences of Latent Variables in Multilevel Data Using Multiple-Group Multilevel CFA and Multilevel MIMIC Modeling.

PubMed

Kim, Eun Sook; Cao, Chunhua

2015-01-01

Considering that group comparisons are common in social science, we examined two latent group mean testing methods when groups of interest were either at the between or within level of multilevel data: multiple-group multilevel confirmatory factor analysis (MG ML CFA) and multilevel multiple-indicators multiple-causes modeling (ML MIMIC). The performance of these methods were investigated through three Monte Carlo studies. In Studies 1 and 2, either factor variances or residual variances were manipulated to be heterogeneous between groups. In Study 3, which focused on within-level multiple-group analysis, six different model specifications were considered depending on how to model the intra-class group correlation (i.e., correlation between random effect factors for groups within cluster). The results of simulations generally supported the adequacy of MG ML CFA and ML MIMIC for multiple-group analysis with multilevel data. The two methods did not show any notable difference in the latent group mean testing across three studies. Finally, a demonstration with real data and guidelines in selecting an appropriate approach to multilevel multiple-group analysis are provided.

SDG and qualitative trend based model multiple scale validation

NASA Astrophysics Data System (ADS)

Gao, Dong; Xu, Xin; Yin, Jianjin; Zhang, Hongyu; Zhang, Beike

2017-09-01

Verification, Validation and Accreditation (VV&A) is key technology of simulation and modelling. For the traditional model validation methods, the completeness is weak; it is carried out in one scale; it depends on human experience. The SDG (Signed Directed Graph) and qualitative trend based multiple scale validation is proposed. First the SDG model is built and qualitative trends are added to the model. And then complete testing scenarios are produced by positive inference. The multiple scale validation is carried out by comparing the testing scenarios with outputs of simulation model in different scales. Finally, the effectiveness is proved by carrying out validation for a reactor model.

Regression Models for the Analysis of Longitudinal Gaussian Data from Multiple Sources

PubMed Central

O’Brien, Liam M.; Fitzmaurice, Garrett M.

2006-01-01

We present a regression model for the joint analysis of longitudinal multiple source Gaussian data. Longitudinal multiple source data arise when repeated measurements are taken from two or more sources, and each source provides a measure of the same underlying variable and on the same scale. This type of data generally produces a relatively large number of observations per subject; thus estimation of an unstructured covariance matrix often may not be possible. We consider two methods by which parsimonious models for the covariance can be obtained for longitudinal multiple source data. The methods are illustrated with an example of multiple informant data arising from a longitudinal interventional trial in psychiatry. PMID:15726666

Log-Multiplicative Association Models as Item Response Models

ERIC Educational Resources Information Center

Anderson, Carolyn J.; Yu, Hsiu-Ting

2007-01-01

Log-multiplicative association (LMA) models, which are special cases of log-linear models, have interpretations in terms of latent continuous variables. Two theoretical derivations of LMA models based on item response theory (IRT) arguments are presented. First, we show that Anderson and colleagues (Anderson & Vermunt, 2000; Anderson & Bockenholt,…

Multiple parton interactions and production of charged particles up to the intermediate-pT range in high-multiplicity p p events at the LHC

NASA Astrophysics Data System (ADS)

Kar, Somnath; Choudhury, Subikash; Muhuri, Sanjib; Ghosh, Premomoy

2017-01-01

Satisfactory description of data by hydrodynamics-motivated models, as has been reported recently by experimental collaborations at the LHC, confirm "collectivity" in high-multiplicity proton-proton (p p ) collisions. Notwithstanding this, a detailed study of high-multiplicity p p data in other approaches or models is essential for better understanding of the specific phenomenon. In this study, the focus is on a pQCD-inspired multiparton interaction (MPI) model, including a color reconnection (CR) scheme as implemented in the Monte Carlo code, PYTHIA8 tune 4C. The MPI with the color reconnection reproduces the dependence of the mean transverse momentum ⟨pT⟩ on the charged particle multiplicity Nch in p p collisions at the LHC, providing an alternate explanation to the signature of "hydrodynamic collectivity" in p p data. It is, therefore, worth exploring how this model responds to other related features of high-multiplicity p p events. This comparative study with recent experimental results demonstrates the limitations of the model in explaining some of the prominent features of the final-state charged particles up to the intermediate-pT (pT<2.0 GeV /c ) range in high-multiplicity p p events.

Multiple-path model of spectral reflectance of a dyed fabric.

PubMed

Rogers, Geoffrey; Dalloz, Nicolas; Fournel, Thierry; Hebert, Mathieu

2017-05-01

Experimental results are presented of the spectral reflectance of a dyed fabric as analyzed by a multiple-path model of reflection. The multiple-path model provides simple analytic expressions for reflection and transmission of turbid media by applying the Beer-Lambert law to each path through the medium and summing over all paths, each path weighted by its probability. The path-length probability is determined by a random-walk analysis. The experimental results presented here show excellent agreement with predictions made by the model.

A latent class multiple constraint multiple discrete-continuous extreme value model of time use and goods consumption.

DOT National Transportation Integrated Search

2016-06-01

This paper develops a microeconomic theory-based multiple discrete continuous choice model that considers: (a) that both goods consumption and time allocations (to work and non-work activities) enter separately as decision variables in the utility fu...

The Research of Multiple Attenuation Based on Feedback Iteration and Independent Component Analysis

NASA Astrophysics Data System (ADS)

Xu, X.; Tong, S.; Wang, L.

2017-12-01

How to solve the problem of multiple suppression is a difficult problem in seismic data processing. The traditional technology for multiple attenuation is based on the principle of the minimum output energy of the seismic signal, this criterion is based on the second order statistics, and it can't achieve the multiple attenuation when the primaries and multiples are non-orthogonal. In order to solve the above problems, we combine the feedback iteration method based on the wave equation and the improved independent component analysis (ICA) based on high order statistics to suppress the multiple waves. We first use iterative feedback method to predict the free surface multiples of each order. Then, in order to predict multiples from real multiple in amplitude and phase, we design an expanded pseudo multi-channel matching filtering method to get a more accurate matching multiple result. Finally, we present the improved fast ICA algorithm which is based on the maximum non-Gauss criterion of output signal to the matching multiples and get better separation results of the primaries and the multiples. The advantage of our method is that we don't need any priori information to the prediction of the multiples, and can have a better separation result. The method has been applied to several synthetic data generated by finite-difference model technique and the Sigsbee2B model multiple data, the primaries and multiples are non-orthogonal in these models. The experiments show that after three to four iterations, we can get the perfect multiple results. Using our matching method and Fast ICA adaptive multiple subtraction, we can not only effectively preserve the effective wave energy in seismic records, but also can effectively suppress the free surface multiples, especially the multiples related to the middle and deep areas.

Design and modeling of sustainable bioethanol supply chain by minimizing the total ecological footprint in life cycle perspective.

PubMed

Ren, Jingzheng; Manzardo, Alessandro; Toniolo, Sara; Scipioni, Antonio; Tan, Shiyu; Dong, Lichun; Gao, Suzhao

2013-10-01

The purpose of this paper is to develop a model for designing the most sustainable bioethanol supply chain. Taking into consideration of the possibility of multiple-feedstock, multiple transportation modes, multiple alternative technologies, multiple transport patterns and multiple waste disposal manners in bioethanol systems, this study developed a model for designing the most sustainable bioethanol supply chain by minimizing the total ecological footprint under some prerequisite constraints including satisfying the goal of the stakeholders', the limitation of resources and energy, the capacity of warehouses, the market demand and some technological constraints. And an illustrative case of multiple-feedstock bioethanol system has been studied by the proposed method, and a global best solution by which the total ecological footprint is the minimal has been obtained. Copyright © 2013 Elsevier Ltd. All rights reserved.

Double-multiple streamtube model for Darrieus in turbines

NASA Technical Reports Server (NTRS)

Paraschivoiu, I.

1981-01-01

An analytical model is proposed for calculating the rotor performance and aerodynamic blade forces for Darrieus wind turbines with curved blades. The method of analysis uses a multiple-streamtube model, divided into two parts: one modeling the upstream half-cycle of the rotor and the other, the downstream half-cycle. The upwind and downwind components of the induced velocities at each level of the rotor were obtained using the principle of two actuator disks in tandem. Variation of the induced velocities in the two parts of the rotor produces larger forces in the upstream zone and smaller forces in the downstream zone. Comparisons of the overall rotor performance with previous methods and field test data show the important improvement obtained with the present model. The calculations were made using the computer code CARDAA developed at IREQ. The double-multiple streamtube model presented has two major advantages: it requires a much shorter computer time than the three-dimensional vortex model and is more accurate than multiple-streamtube model in predicting the aerodynamic blade loads.

Accounting for heterogeneity in meta-analysis using a multiplicative model-an empirical study.

PubMed

Mawdsley, David; Higgins, Julian P T; Sutton, Alex J; Abrams, Keith R

2017-03-01

In meta-analysis, the random-effects model is often used to account for heterogeneity. The model assumes that heterogeneity has an additive effect on the variance of effect sizes. An alternative model, which assumes multiplicative heterogeneity, has been little used in the medical statistics community, but is widely used by particle physicists. In this paper, we compare the two models using a random sample of 448 meta-analyses drawn from the Cochrane Database of Systematic Reviews. In general, differences in goodness of fit are modest. The multiplicative model tends to give results that are closer to the null, with a narrower confidence interval. Both approaches make different assumptions about the outcome of the meta-analysis. In our opinion, the selection of the more appropriate model will often be guided by whether the multiplicative model's assumption of a single effect size is plausible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Algorithms for output feedback, multiple-model, and decentralized control problems

NASA Technical Reports Server (NTRS)

Halyo, N.; Broussard, J. R.

1984-01-01

The optimal stochastic output feedback, multiple-model, and decentralized control problems with dynamic compensation are formulated and discussed. Algorithms for each problem are presented, and their relationship to a basic output feedback algorithm is discussed. An aircraft control design problem is posed as a combined decentralized, multiple-model, output feedback problem. A control design is obtained using the combined algorithm. An analysis of the design is presented.

Optimal design of compact and connected nature reserves for multiple species.

PubMed

Wang, Yicheng; Önal, Hayri

2016-04-01

When designing a conservation reserve system for multiple species, spatial attributes of the reserves must be taken into account at species level. The existing optimal reserve design literature considers either one spatial attribute or when multiple attributes are considered the analysis is restricted only to one species. We built a linear integer programing model that incorporates compactness and connectivity of the landscape reserved for multiple species. The model identifies multiple reserves that each serve a subset of target species with a specified coverage probability threshold to ensure the species' long-term survival in the reserve, and each target species is covered (protected) with another probability threshold at the reserve system level. We modeled compactness by minimizing the total distance between selected sites and central sites, and we modeled connectivity of a selected site to its designated central site by selecting at least one of its adjacent sites that has a nearer distance to the central site. We considered structural distance and functional distances that incorporated site quality between sites. We tested the model using randomly generated data on 2 species, one ground species that required structural connectivity and the other an avian species that required functional connectivity. We applied the model to 10 bird species listed as endangered by the state of Illinois (U.S.A.). Spatial coherence and selection cost of the reserves differed substantially depending on the weights assigned to these 2 criteria. The model can be used to design a reserve system for multiple species, especially species whose habitats are far apart in which case multiple disjunct but compact and connected reserves are advantageous. The model can be modified to increase or decrease the distance between reserves to reduce or promote population connectivity. © 2015 Society for Conservation Biology.

Modeling Errors in Daily Precipitation Measurements: Additive or Multiplicative?

NASA Technical Reports Server (NTRS)

Tian, Yudong; Huffman, George J.; Adler, Robert F.; Tang, Ling; Sapiano, Matthew; Maggioni, Viviana; Wu, Huan

2013-01-01

The definition and quantification of uncertainty depend on the error model used. For uncertainties in precipitation measurements, two types of error models have been widely adopted: the additive error model and the multiplicative error model. This leads to incompatible specifications of uncertainties and impedes intercomparison and application.In this letter, we assess the suitability of both models for satellite-based daily precipitation measurements in an effort to clarify the uncertainty representation. Three criteria were employed to evaluate the applicability of either model: (1) better separation of the systematic and random errors; (2) applicability to the large range of variability in daily precipitation; and (3) better predictive skills. It is found that the multiplicative error model is a much better choice under all three criteria. It extracted the systematic errors more cleanly, was more consistent with the large variability of precipitation measurements, and produced superior predictions of the error characteristics. The additive error model had several weaknesses, such as non constant variance resulting from systematic errors leaking into random errors, and the lack of prediction capability. Therefore, the multiplicative error model is a better choice.

Improving Multiple Fault Diagnosability using Possible Conflicts

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Biswas, Gautam; Koutsoukos, Xenofon; Pulido, Belarmino

2012-01-01

Multiple fault diagnosis is a difficult problem for dynamic systems. Due to fault masking, compensation, and relative time of fault occurrence, multiple faults can manifest in many different ways as observable fault signature sequences. This decreases diagnosability of multiple faults, and therefore leads to a loss in effectiveness of the fault isolation step. We develop a qualitative, event-based, multiple fault isolation framework, and derive several notions of multiple fault diagnosability. We show that using Possible Conflicts, a model decomposition technique that decouples faults from residuals, we can significantly improve the diagnosability of multiple faults compared to an approach using a single global model. We demonstrate these concepts and provide results using a multi-tank system as a case study.