Sample records for consequence analysis modifications

  1. System Safety and the Unintended Consequence

    NASA Technical Reports Server (NTRS)

    Watson, Clifford

    2012-01-01

    The analysis and identification of risks often result in design changes or modification of operational steps. This paper identifies the potential of unintended consequences as an over-looked result of these changes. Examples of societal changes such as prohibition, regulatory changes including mandating lifeboats on passenger ships, and engineering proposals or design changes to automobiles and spaceflight hardware are used to demonstrate that the System Safety Engineer must be cognizant of the potential for unintended consequences as a result of an analysis. Conclusions of the report indicate the need for additional foresight and consideration of the potential effects of analysis-driven design, processing changes, and/or operational modifications.

  2. Landscape changes as a factor affecting the course and consequences of extreme floods in the Otava river basin, Czech Republic.

    PubMed

    Langhammer, Jakub; Vilímek, Vít

    2008-09-01

    The paper presents the analysis of anthropogenical modifications of the landscape in relation to the course and consequences of floods. The research was conducted in the Otava river basin which represents the core zone of the extreme flood in August 2002 in Central Europe. The analysis was focused on the key indicators of landscape modification potentially affecting the runoff process - the long-term changes of land-use, changes of land cover structure, land drainage, historical shortening of the river network and the modifications of streams and floodplains. The information on intensity and spatial distribution of modifications was derived from different data sources--historical maps, available GIS data, remote sensing and field mapping. The results revealed a high level of spatial diversity of anthropogenical modifications in different parts of the river basin. The intensive modifications in most of indicators were concentrated in the lowland region of the river basin due to its agricultural use; however important changes were also recorded in the headwater region of the basin. The high spatial diversity of the modifications may result in their varying effect on the course and consequences of floods in different parts of the river basin. This effect is demonstrated by the cluster analysis based on the matrix of indicators of stream and floodplain modification, physiogeographical characteristics and geomorphological evidences of the flood in August 2002, derived from the individual thematic layers using GIS.

  3. Surface modification of ferritic steels using MEVVA and duoplasmatron ion sources

    NASA Astrophysics Data System (ADS)

    Kulevoy, Timur V.; Chalyhk, Boris B.; Fedin, Petr A.; Sitnikov, Alexey L.; Kozlov, Alexander V.; Kuibeda, Rostislav P.; Andrianov, Stanislav L.; Orlov, Nikolay N.; Kravchuk, Konstantin S.; Rogozhkin, Sergey V.; Useinov, Alexey S.; Oks, Efim M.; Bogachev, Alexey A.; Nikitin, Alexander A.; Iskandarov, Nasib A.; Golubev, Alexander A.

    2016-02-01

    Metal Vapor Vacuum Arc (MEVVA) ion source (IS) is a unique tool for production of high intensity metal ion beam that can be used for material surface modification. From the other hand, the duoplasmatron ion source provides the high intensity gas ion beams. The MEVVA and duoplasmatron IS developed in Institute for Theoretical and Experimental Physics were used for the reactor steel surface modification experiments. Response of ferritic-martensitic steel specimens on titanium and nitrogen ions implantation and consequent vacuum annealing was investigated. Increase in microhardness of near surface region of irradiated specimens was observed. Local chemical analysis shows atom mixing and redistribution in the implanted layer followed with formation of ultrafine precipitates after annealing.

  4. Civilizing the 'Barbarian': a critical analysis of behaviour modification programmes in forensic psychiatry settings.

    PubMed

    Holmes, Dave; Murray, Stuart J

    2011-04-01

    Drawing on the works of Erving Goffman and Michel Foucault, this article presents part of the results of a qualitative study conducted in a forensic psychiatry setting. For many years, behaviour modification programmes (BMPs) have been subjected to scrutiny and harsh criticism on the part of researchers, clinicians and professional organizations. Nevertheless, BMPs continue to be in vogue in some 'total' institutions, such as psychiatric hospitals and prisons. Discourse analysis of mute evidence available in situ was used to critically look at behaviour modification programmes. Compelling examples of behaviour modification care plans are used to illustrate our critical analysis and to support our claim that BMPs violate both scientific and ethical norms in the name of doing 'what is best' for the patients. We argue that the continued use of BMPs is not only flawed from a scientific perspective, but constitutes an unethical approach to the management of nursing care for mentally ill offenders. Nurse managers need to be aware that BMPs violate ethical standards in nursing. As a consequence, they should overtly question the use of these approaches in psychiatric nursing. © 2011 The Authors. Journal compilation © 2011 Blackwell Publishing Ltd.

  5. Histone modification: cause or cog?

    PubMed

    Henikoff, Steven; Shilatifard, Ali

    2011-10-01

    Histone modifications are key components of chromatin packaging but whether they constitute a 'code' has been contested. We believe that the central issue is causality: are histone modifications responsible for differences between chromatin states, or are differences in modifications mostly consequences of dynamic processes, such as transcription and nucleosome remodeling? We find that inferences of causality are often based on correlation and that patterns of some key histone modifications are more easily explained as consequences of nucleosome disruption in the presence of histone modifying enzymes. We suggest that the 35-year-old DNA accessibility paradigm provides a mechanistically sound basis for understanding the role of nucleosomes in gene regulation and epigenetic inheritance. Based on this view, histone modifications and variants contribute to diversification of a chromatin landscape shaped by dynamic processes that are driven primarily by transcription and nucleosome remodeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Domesticated, Genetically Engineered, and Wild Plant Relatives Exhibit Unintended Phenotypic Differences: A Comparative Meta-Analysis Profiling Rice, Canola, Maize, Sunflower, and Pumpkin

    PubMed Central

    Hernández-Terán, Alejandra; Wegier, Ana; Benítez, Mariana; Lira, Rafael; Escalante, Ana E.

    2017-01-01

    Agronomic management of plants is a powerful evolutionary force acting on their populations. The management of cultivated plants is carried out by the traditional process of human selection or plant breeding and, more recently, by the technologies used in genetic engineering (GE). Even though crop modification through GE is aimed at specific traits, it is possible that other non-target traits can be affected by genetic modification due to the complex regulatory processes of plant metabolism and development. In this study, we conducted a meta-analysis profiling the phenotypic consequences of plant breeding and GE, and compared modified cultivars with wild relatives in five crops of global economic and cultural importance: rice, maize, canola, sunflower, and pumpkin. For these five species, we analyzed the literature with documentation of phenotypic traits that are potentially related to fitness for the same species in comparable conditions. The information was analyzed to evaluate whether the different processes of modification had influenced the phenotype in such a way as to cause statistical differences in the state of specific phenotypic traits or grouping of the organisms depending on their genetic origin [wild, domesticated with genetic engineering (domGE), and domesticated without genetic engineering (domNGE)]. In addition, we tested the hypothesis that, given that transgenic plants are a construct designed to impact, in many cases, a single trait of the plant (e.g., lepidopteran resistance), the phenotypic differences between domGE and domNGE would be either less (or inexistent) than between the wild and domesticated relatives (either domGE or domNGE). We conclude that (1) genetic modification (either by selective breeding or GE) can be traced phenotypically when comparing wild relatives with their domesticated relatives (domGE and domNGE) and (2) the existence and the magnitude of the phenotypic differences between domGE and domNGE of the same crop suggest consequences of genetic modification beyond the target trait(s). PMID:29259610

  7. Speech transformation system (spectrum and/or excitation) without pitch extraction

    NASA Astrophysics Data System (ADS)

    Seneff, S.

    1980-07-01

    A speech analysis synthesis system was developed which is capable of independent manipulation of the fundamental frequency and spectral envelope of a speech waveform. The system deconvolved the original speech with the spectral envelope estimate to obtain a model for the excitation, explicit pitch extraction was not required and as a consequence, the transformed speech was more natural sounding than would be the case if the excitation were modeled as a sequence of pulses. It is shown that the system has applications in the areas of voice modifications, baseband excited vocoders, time scale modifications, and frequency compression as an aid to the partially deaf.

  8. Taking Another Look at Behavior Modification and Assertive Discipline.

    ERIC Educational Resources Information Center

    Palardy, J. Michael

    1996-01-01

    Behavior modification and assertive discipline approaches use rewards and negative consequences (extinction procedures) to deal with students' maladaptive behavior. Behavior modification has significant limitations, as it treats symptoms, not causes; yields only short-term benefits; has limited transfer value for other environments; and values…

  9. Long-term psychological consequences of symptomatic pulmonary embolism: a qualitative study.

    PubMed

    Noble, Simon; Lewis, Rhian; Whithers, Jodie; Lewis, Sarah; Bennett, Paul

    2014-04-02

    To explore the psychological consequences of experiencing symptomatic pulmonary embolism (PE). Qualitative interview-based study using interpretative phenomenological analysis. Outpatients who attended an anticoagulation clinic in a district general hospital. Patients attending an anticoagulation clinic following hospital admission for symptomatic PE were approached to participate. A total of 9 (4 women, 5 men) of 11 patients approached agreed to be interviewed. Participants were aged between 26 and 72 years and had previously experienced a PE between 9 and 60 months (median=26 months, mean=24 months). Audiotaped semistructured qualitative interviews were undertaken to explore participants experiences of having a PE and how it had affected their lives since. Data were transcribed and analysed using interpretative phenomenological analysis to identify emergent themes. Three major themes with associated subthemes were identified. Participants described having a PE as a life-changing experience comprising initial shock, followed by feeling of loss of self, life-changing decisions and behaviour modification. Features of post-traumatic stress disorder (PTSD) were described with flashbacks, hypervigilance and intrusive thoughts being most prevalent. Participants identified several areas of support needed for such patients including easier access to support through information giving and emotional support. Long-term consequences of venous thromboembolism go beyond the physical alone. Patients describe experiencing symptomatic PE to be a life-changing distressing event leading to behaviour modification and in some PTSD. It is likely that earlier psychological intervention may reduce such long-term sequelae.

  10. Assessing the Potential of Land Use Modification to Mitigate Ambient NO₂ and Its Consequences for Respiratory Health.

    PubMed

    Rao, Meenakshi; George, Linda A; Shandas, Vivek; Rosenstiel, Todd N

    2017-07-10

    Understanding how local land use and land cover (LULC) shapes intra-urban concentrations of atmospheric pollutants-and thus human health-is a key component in designing healthier cities. Here, NO₂ is modeled based on spatially dense summer and winter NO₂ observations in Portland-Hillsboro-Vancouver (USA), and the spatial variation of NO₂ with LULC investigated using random forest, an ensemble data learning technique. The NO 2 random forest model, together with BenMAP, is further used to develop a better understanding of the relationship among LULC, ambient NO₂ and respiratory health. The impact of land use modifications on ambient NO₂, and consequently on respiratory health, is also investigated using a sensitivity analysis. We find that NO₂ associated with roadways and tree-canopied areas may be affecting annual incidence rates of asthma exacerbation in 4-12 year olds by +3000 per 100,000 and -1400 per 100,000, respectively. Our model shows that increasing local tree canopy by 5% may reduce local incidences rates of asthma exacerbation by 6%, indicating that targeted local tree-planting efforts may have a substantial impact on reducing city-wide incidence of respiratory distress. Our findings demonstrate the utility of random forest modeling in evaluating LULC modifications for enhanced respiratory health.

  11. Rice epigenomics and epigenetics: challenges and opportunities.

    PubMed

    Chen, Xiangsong; Zhou, Dao-Xiu

    2013-05-01

    During recent years rice genome-wide epigenomic information such as DNA methylation and histone modifications, which are important for genome activity has been accumulated. The function of a number of rice epigenetic regulators has been studied, many of which are found to be involved in a diverse range of developmental and stress-responsive pathways. Analysis of epigenetic variations among different rice varieties indicates that epigenetic modification may lead to inheritable phenotypic variation. Characterizing phenotypic consequences of rice epigenomic variations and the underlining chromatin mechanism and identifying epialleles related to important agronomic traits may provide novel strategies to enhance agronomically favorable traits and grain productivity in rice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Dynamic event tree analysis with the SAS4A/SASSYS-1 safety analysis code

    DOE PAGES

    Jankovsky, Zachary K.; Denman, Matthew R.; Aldemir, Tunc

    2018-02-02

    The consequences of a transient in an advanced sodium-cooled fast reactor are difficult to capture with the traditional approach to probabilistic risk assessment (PRA). Numerous safety-relevant systems are passive and may have operational states that cannot be represented by binary success or failure. In addition, the specific order and timing of events may be crucial which necessitates the use of dynamic PRA tools such as ADAPT. The modifications to the SAS4A/SASSYS-1 sodium-cooled fast reactor safety analysis code for linking it to ADAPT to perform a dynamic PRA are described. A test case is used to demonstrate the linking process andmore » to illustrate the type of insights that may be gained with this process. Finally, newly-developed dynamic importance measures are used to assess the significance of reactor parameters/constituents on calculated consequences of initiating events.« less

  13. Dynamic event tree analysis with the SAS4A/SASSYS-1 safety analysis code

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

    Jankovsky, Zachary K.; Denman, Matthew R.; Aldemir, Tunc

    The consequences of a transient in an advanced sodium-cooled fast reactor are difficult to capture with the traditional approach to probabilistic risk assessment (PRA). Numerous safety-relevant systems are passive and may have operational states that cannot be represented by binary success or failure. In addition, the specific order and timing of events may be crucial which necessitates the use of dynamic PRA tools such as ADAPT. The modifications to the SAS4A/SASSYS-1 sodium-cooled fast reactor safety analysis code for linking it to ADAPT to perform a dynamic PRA are described. A test case is used to demonstrate the linking process andmore » to illustrate the type of insights that may be gained with this process. Finally, newly-developed dynamic importance measures are used to assess the significance of reactor parameters/constituents on calculated consequences of initiating events.« less

  14. Improving yield and reliability of FIB modifications using electrical testing

    NASA Astrophysics Data System (ADS)

    Desplats, Romain; Benbrik, Jamel; Benteo, Bruno; Perdu, Philippe

    1998-08-01

    Focused Ion Beam technology has two main areas of application for ICs: modification and preparation for technological analysis. The most solicited area is modification. This involves physically modifying a circuit by cutting lines and creating new ones in order to change the electrical function of the circuit. IC planar technologies have an increasing number of metal interconnections making FIB modifications more complex and decreasing their changes of success. The yield of FIB operations on ICs reflects a downward trend that imposes a greater number of circuits to be modified in order to successfully correct a small number of them. This requires extended duration, which is not compatible with production line turn around times. To respond to this problem, two solutions can be defined: either, reducing the duration of each FIB operation or increasing the success rate of FIB modifications. Since reducing the time depends mainly on FIB operator experience, insuring a higher success rate represents a more crucial aspect as both experienced and novice operators could benefit from this improvement. In order to insure successful modifications, it is necessary to control each step of a FIB operation. To do this, we have developed a new method using in situ electrical testing which has a direct impact on the yield of FIB modifications. We will present this innovative development through a real case study of a CMOS ASIC for high-speed communications. Monitoring the electrical behavior at each step in a FIB operation makes it possible to reduce the number of circuits to be modified and consequently reduces system costs thanks to better yield control. Knowing the internal electrical behavior also gives us indications about the impact on reliability of FIB modified circuits. Finally, this approach can be applied to failure analysis and FIB operations on flip chip circuits.

  15. Modification of the SAS4A Safety Analysis Code for Integration with the ADAPT Discrete Dynamic Event Tree Framework.

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

    Jankovsky, Zachary Kyle; Denman, Matthew R.

    It is difficult to assess the consequences of a transient in a sodium-cooled fast reactor (SFR) using traditional probabilistic risk assessment (PRA) methods, as numerous safety-related sys- tems have passive characteristics. Often there is significant dependence on the value of con- tinuous stochastic parameters rather than binary success/failure determinations. One form of dynamic PRA uses a system simulator to represent the progression of a transient, tracking events through time in a discrete dynamic event tree (DDET). In order to function in a DDET environment, a simulator must have characteristics that make it amenable to changing physical parameters midway through themore » analysis. The SAS4A SFR system analysis code did not have these characteristics as received. This report describes the code modifications made to allow dynamic operation as well as the linking to a Sandia DDET driver code. A test case is briefly described to demonstrate the utility of the changes.« less

  16. Assessing the Potential of Land Use Modification to Mitigate Ambient NO2 and Its Consequences for Respiratory Health

    PubMed Central

    Rao, Meenakshi; George, Linda A.; Shandas, Vivek; Rosenstiel, Todd N.

    2017-01-01

    Understanding how local land use and land cover (LULC) shapes intra-urban concentrations of atmospheric pollutants—and thus human health—is a key component in designing healthier cities. Here, NO2 is modeled based on spatially dense summer and winter NO2 observations in Portland-Hillsboro-Vancouver (USA), and the spatial variation of NO2 with LULC investigated using random forest, an ensemble data learning technique. The NO2 random forest model, together with BenMAP, is further used to develop a better understanding of the relationship among LULC, ambient NO2 and respiratory health. The impact of land use modifications on ambient NO2, and consequently on respiratory health, is also investigated using a sensitivity analysis. We find that NO2 associated with roadways and tree-canopied areas may be affecting annual incidence rates of asthma exacerbation in 4–12 year olds by +3000 per 100,000 and −1400 per 100,000, respectively. Our model shows that increasing local tree canopy by 5% may reduce local incidences rates of asthma exacerbation by 6%, indicating that targeted local tree-planting efforts may have a substantial impact on reducing city-wide incidence of respiratory distress. Our findings demonstrate the utility of random forest modeling in evaluating LULC modifications for enhanced respiratory health. PMID:28698523

  17. Optical characterization of randomly microrough surfaces covered with very thin overlayers using effective medium approximation and Rayleigh-Rice theory

    NASA Astrophysics Data System (ADS)

    Ohlídal, Ivan; Vohánka, Jiří; Čermák, Martin; Franta, Daniel

    2017-10-01

    The modification of the effective medium approximation for randomly microrough surfaces covered by very thin overlayers based on inhomogeneous fictitious layers is formulated. The numerical analysis of this modification is performed using simulated ellipsometric data calculated using the Rayleigh-Rice theory. The system used to perform this numerical analysis consists of a randomly microrough silicon single crystal surface covered with a SiO2 overlayer. A comparison to the effective medium approximation based on homogeneous fictitious layers is carried out within this numerical analysis. For ellipsometry of the system mentioned above the possibilities and limitations of both the effective medium approximation approaches are discussed. The results obtained by means of the numerical analysis are confirmed by the ellipsometric characterization of two randomly microrough silicon single crystal substrates covered with native oxide overlayers. It is shown that the effective medium approximation approaches for this system exhibit strong deficiencies compared to the Rayleigh-Rice theory. The practical consequences implied by these results are presented. The results concerning the random microroughness are verified by means of measurements performed using atomic force microscopy.

  18. Comparison Of Intake Gate Closure Methods At Lower Granite, Little Goose, Lower Monumental, And Mcnary Dams Using Risk-Based Analysis

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

    Gore, Bryan F.; Blackburn, Tyrone R.; Heasler, Patrick G.

    2001-01-19

    The objective of this report is to compare the benefits and costs of modifications proposed for intake gate closure systems at four hydroelectric stations on the Lower Snake and Upper Columbia Rivers in the Walla Walla District that are unable to meet the COE 10-minute closure rule due to the installation of fish screens. The primary benefit of the proposed modifications is to reduce the risk of damage to the station and environs when emergency intake gate closure is required. Consequently, this report presents the results and methodology of an extensive risk analysis performed to assess the reliability of powerhousemore » systems and the costs and timing of potential damages resulting from events requiring emergency intake gate closure. As part of this analysis, the level of protection provided by the nitrogen emergency closure system was also evaluated. The nitrogen system was the basis for the original recommendation to partially disable the intake gate systems. The risk analysis quantifies this protection level.« less

  19. Nature, frequency and determinants of prescription modifications in Dutch community pharmacies

    PubMed Central

    Buurma, Henk; de Smet, Peter A G M; van den Hoff, Olga P; Egberts, Antoine C G

    2001-01-01

    Aims To examine the nature, frequency and determinants of prescription modifications in Dutch community pharmacies. Methods A prospective case-control study comparing modified prescriptions with nonmodified prescriptions was carried out in 141 Dutch community pharmacies. 2014 modified prescriptions (cases), collected in the selected pharmacies on a predetermined day in a specific period (25th February until 12th March 1999) and 2581 nonmodified prescriptions (controls) randomly selected on the same day were studied. The nature and frequency of prescription modifications and patient, drug and prescriber related determinants for a modified prescription were assessed. Results The overall incidence of prescription modifications was 4.3%, with a mean of 14.3 modifications per pharmacy per day. For prescription only medicines (POM) the incidence was 4.9%. The majority of POM modifications concerned a clarification (71.8%). In 22.2% a prescription could potentially have had clinical consequences when not altered; in more than half of the latter it concerned a dose error (13.7% of all cases). POM prescriptions of patients of 40–65 years had a significantly lower chance of modification compared with those of younger people (OR = 0.74 [0.64–0.86]). With respect to medication-class, we found a higher chance of POM modifications in the respiratory domain (OR = 1.48 [1.23-1.79]) and a decreased chance for nervous system POMs (OR = 0.71 [0.61–0.83]). With regard to prescriber-related determinants modifications were found three times more often in non printed prescriptions than in printed ones (OR = 3.30 [2.90-3.75]). Compared with prescriptions by the patient's own GP, prescriptions of specialists (OR = 1.82 [1.57-2.11]), other GP's (OR = 1.49 [1.02-2.17]) and other prescribers such as dentists and midwives (OR = 1.95 [1.06-3.57]) gave a higher probability of prescription modifications. When a GP had no on-line access to the computer of the pharmacy the chance of a modification was also higher (OR = 1.61 [1.33-1.94]). Multivariate analysis revealed that a nonprinted prescription was the strongest independent determinant of prescription modifications (OR = 3.32 [2.87-3.84]), remaining so after adjustment for GP computer link to the pharmacy and for type of prescriber. Conclusions At least 30% of Dutch community pharmacies corrected 2.8 POM prescriptions per pharmacy per working day, which could potentially have had clinical consequences if not altered. If the study sample is representative for The Netherlands, Dutch community pharmacies correct a total of approximately 4400 of these prescriptions per working day. Using computerized systems to generate prescriptions is an important strategy to reduce the incidence of prescription errors. PMID:11453894

  20. Characterization of O-acetylation in sialoglycans by MALDI-MS using a combination of methylamidation and permethylation

    NASA Astrophysics Data System (ADS)

    Wu, Zhaoguan; Li, Henghui; Zhang, Qiwei; Liu, Xin; Zheng, Qi; Li, Jianjun

    2017-04-01

    O-Acetylation of sialic acid in protein N-glycans is an important modification and can occur at either 4-, 7-, 8- or 9-position in various combinations. This modification is usually labile under alkaline reaction conditions. Consequently, a permethylation-based analytical method, which has been widely used in glycomics studies, is not suitable for profiling O-acetylation of sialic acids due to the harsh reaction conditions. Alternatively, methylamidation can be used for N-glycan analysis without affecting the base-labile modification of sialic acid. In this report, we applied both permethylation and methylamidation approaches to the analysis of O-acetylation in sialic acids. It has been demonstrated that methylamidation not only stabilizes sialic acids during MALDI processing but also allow for characterization of their O-acetylation pattern. In addition, LC-MS/MS experiments were carried out to distinguish between the O-acetylated glycans with potential isomeric structures. The repeatability of methylamidation was examined to evaluate the applicability of the approach to profiling of O-acetylation in sialic acids. In conclusion, the combination of methylamidation and permethylation methodology is a powerful MALDI-TOF MS-based tool for profiling O-acetylation in sialic acids applicable to screening of N-glycans.

  1. Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications.

    PubMed

    Porter, Joseph J; Mehl, Ryan A

    2018-01-01

    Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described.

  2. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  3. Monster potential meets potential monster: pros and cons of deploying genetically modified microalgae for biofuels production.

    PubMed

    Flynn, K J; Mitra, A; Greenwell, H C; Sui, J

    2013-02-06

    Biofuels production from microalgae attracts much attention but remains an unproven technology. We explore routes to enhance production through modifications to a range of generic microalgal physiological characteristics. Our analysis shows that biofuels production may be enhanced ca fivefold through genetic modification (GM) of factors affecting growth rate, respiration, photoacclimation, photosynthesis efficiency and the minimum cell quotas for nitrogen and phosphorous (N : C and P : C). However, simulations indicate that the ideal GM microalgae for commercial deployment could, on escape to the environment, become a harmful algal bloom species par excellence, with attendant risks to ecosystems and livelihoods. In large measure, this is because an organism able to produce carbohydrate and/or lipid at high rates, providing stock metabolites for biofuels production, will also be able to attain a stoichiometric composition that will be far from optimal as food for the support of zooplankton growth. This composition could suppress or even halt the grazing activity that would otherwise control the microalgal growth in nature. In consequence, we recommend that the genetic manipulation of microalgae, with inherent consequences on a scale comparable to geoengineering, should be considered under strict international regulation.

  4. Monster potential meets potential monster: pros and cons of deploying genetically modified microalgae for biofuels production

    PubMed Central

    Flynn, K. J.; Mitra, A.; Greenwell, H. C.; Sui, J.

    2013-01-01

    Biofuels production from microalgae attracts much attention but remains an unproven technology. We explore routes to enhance production through modifications to a range of generic microalgal physiological characteristics. Our analysis shows that biofuels production may be enhanced ca fivefold through genetic modification (GM) of factors affecting growth rate, respiration, photoacclimation, photosynthesis efficiency and the minimum cell quotas for nitrogen and phosphorous (N : C and P : C). However, simulations indicate that the ideal GM microalgae for commercial deployment could, on escape to the environment, become a harmful algal bloom species par excellence, with attendant risks to ecosystems and livelihoods. In large measure, this is because an organism able to produce carbohydrate and/or lipid at high rates, providing stock metabolites for biofuels production, will also be able to attain a stoichiometric composition that will be far from optimal as food for the support of zooplankton growth. This composition could suppress or even halt the grazing activity that would otherwise control the microalgal growth in nature. In consequence, we recommend that the genetic manipulation of microalgae, with inherent consequences on a scale comparable to geoengineering, should be considered under strict international regulation. PMID:24427510

  5. Progressing from initially ambiguous functional analyses: three case examples.

    PubMed

    Tiger, Jeffrey H; Fisher, Wayne W; Toussaint, Karen A; Kodak, Tiffany

    2009-01-01

    Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman [Iwata, B. A., Dorsey, M. F., Slifer, K. J., Bauman, K. E., & Richman, G. S. (1994). Toward a functional analysis of self-injury. Journal of Applied Behavior Analysis, 27, 197-209 (Reprinted from Analysis and Intervention in Developmental Disabilities, 2, 3-20, 1982)]. These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments.

  6. Epigenomic landscape modified by histone modification correlated with activation of IGF2 gene

    USDA-ARS?s Scientific Manuscript database

    The links of histone post-translational modifications and chromatin structure to cell cycle progression, DNA replication, and overall chromosome functions are very clear. The modulation of genome expression as a consequence of chromatin structural changes is most likely a basic mechanism. The epige...

  7. Glycation, oxidation and glycoxidation of IgG: a biophysical, biochemical, immunological and hematological study.

    PubMed

    Islam, Sidra; Moinuddin; Mir, Abdul Rouf; Raghav, Alok; Habib, Safia; Alam, Khursheed; Ali, Asif

    2017-09-12

    Glycation and oxidation induce structural alterations in the proteins in an interdependent manner with consequent pathological implications. The published literature presents wide range of modifications in conformational characteristics of proteins by glycation and oxidation; however, there is little data that could elaborate the cumulative effect of both the processes. This study has analysed the modifications in IgG by methylglyoxal (MG) (glycative stress), hydroxyl radical ([Formula: see text]) (oxidative stress) and by their combined action i.e. [Formula: see text] treatment of MG glycated IgG (glycoxidation). It further addresses the implications of the altered structural integrity of IgG on its immunological characteristics and impact on haematological parameters in rabbits. Using circular dichroism, FTIR, SDS-PAGE analysis, thioflavin-T fluorescence assay, congo red absorbance analysis, dynamic light scattering, transmission electron microscopy, ELISA, blood cell counts and rectal temperature studies, we report that the glycoxidative modification caused maximum alteration in the IgG as compared to the glycatively and oxidatively modified protein. Far-UV CD results confirmed the highest decline in the beta-pleated sheet content of the protein by glycoxidation. The damage led to the reduced flexibility and enhanced electronic interactions in IgG as observed by near-UV CD. Modifications caused cross-linking and adduct formation in the serum protein. The electron micrograph confirmed amorphous aggregation in modified IgG. The modifications increased the hydrodynamic radius of IgG by allowing the attachment of [Formula: see text] and MG residues. The glycoxidatively modified IgG induced the maximum antibody titres that showed high specificity towards the altered IgG. The glycoxidation of IgG leads to activation of inflammatory pathways.

  8. Does Tropical Cyclone Modification Make Sense? A Decision-Analytic Assessment

    NASA Astrophysics Data System (ADS)

    Klima, K.; Morgan, M. G.; Grossmann, I.

    2009-12-01

    Since the demise of project Stormfury in 1983, little attention has been devoted to the possibility of intentionally modifying tropical cyclones (TC). However, following Hurricane Katrina and three other Category 5 hurricanes (Emily, Rita, and Wilma), which together resulted in at least 2,280 deaths and over $120-billion in damages (Blake et al., 2007), the U.S. Department of Homeland Security (DHS) has recently begun to support an effort to identify and evaluate hurricane mitigation strategies through Project HURRMIT ([http://www.ofcm.noaa.gov/ihc09/Presentations/Session10/s10-01Woodley.ppt]). Using a decision analytic framing and FEMA's HAZUS-MH MR3 damage model (http://www.fema.gov/plan/prevent/hazus/]), this paper asks, how sure must one be that an intervention will reduce TC damages before choosing to undertake a program of modification? The analysis is formulated in probabilistic terms, and assesses net benefits. In contrast to a much earlier application of decision analysis to TC-modification (Howard et al., 1972) , this work uses census data on the value of property at risk, and prior distributions on changing storm behavior based on data from hurricanes approaching the east coast of Florida since 1953. Even before considering both issues of liability that may arise from the fact that a modified storm is no longer "an act of God" as well as unforeseen environmental consequences, our results suggest that while TC modification techniques will likely alter TC behavior, one will have to be significantly more confident of the predictability and effectiveness of modification methods before their use can be justified. This work is supported by the Climate Decision Making Center through a cooperative agreement between the National Science Foundation (SES-0345798) and Carnegie Mellon University.

  9. [Epigenetic alterations in acute lymphoblastic leukemia].

    PubMed

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  10. Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications

    PubMed Central

    2018-01-01

    Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described. PMID:29849913

  11. Proceedings of the conference on coastal erosion and wetland modification in Louisiana: causes, consequences, and options

    USGS Publications Warehouse

    Boesch, Donald F.

    1982-01-01

    This volume contains 16 papers and panel discussions from a conference held in Baton Rouge, La., 5-6 October 1981. The presentations consider the causes and consequences of coastal erosion and wetland modification in Louisiana and the mitigative options available to slow or reverse the rapid rate of coastal land loss. Detailed habitat mapping studies have allowed accurate estimates of coastal habitat change and land loss through 1978. Projections from these rates of change indicate an annual rate of land loss in coastal Louisiana in the early 1980's of approximately 130 km2/yr (50 m2/yr).The projected effects of wetland modification on the bountiful living resources of coastal Louisiana (fisheries, fur and hide bearers and waterfowl) are major because of the close dependence of these resources on estuarine wetlands. These changes and others related to flood protection, transportation and ownership of mineral resources are projected to have extensive social and economic consequences.Options proposed to slow coastal land loss include major and minor diversion of the Mississippi River, barrier island and shoreline restoration protection, hydrological management of wetlands and more restrictive permitting of dredging activities.

  12. Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

    PubMed

    Ren, Xiangkui; Feng, Yakai; Guo, Jintang; Wang, Haixia; Li, Qian; Yang, Jing; Hao, Xuefang; Lv, Juan; Ma, Nan; Li, Wenzhong

    2015-08-07

    Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

  13. Oxidative Modulation of Voltage-Gated Potassium Channels

    PubMed Central

    Sahoo, Nirakar; Hoshi, Toshinori

    2014-01-01

    Abstract Significance: Voltage-gated K+ channels are a large family of K+-selective ion channel protein complexes that open on membrane depolarization. These K+ channels are expressed in diverse tissues and their function is vital for numerous physiological processes, in particular of neurons and muscle cells. Potentially reversible oxidative regulation of voltage-gated K+ channels by reactive species such as reactive oxygen species (ROS) represents a contributing mechanism of normal cellular plasticity and may play important roles in diverse pathologies including neurodegenerative diseases. Recent Advances: Studies using various protocols of oxidative modification, site-directed mutagenesis, and structural and kinetic modeling provide a broader phenomenology and emerging mechanistic insights. Critical Issues: Physicochemical mechanisms of the functional consequences of oxidative modifications of voltage-gated K+ channels are only beginning to be revealed. In vivo documentation of oxidative modifications of specific amino-acid residues of various voltage-gated K+ channel proteins, including the target specificity issue, is largely absent. Future Directions: High-resolution chemical and proteomic analysis of ion channel proteins with respect to oxidative modification combined with ongoing studies on channel structure and function will provide a better understanding of how the function of voltage-gated K+ channels is tuned by ROS and the corresponding reducing enzymes to meet cellular needs. Antioxid. Redox Signal. 21, 933–952. PMID:24040918

  14. Female genital mutilation/cutting type IV in Cambodia: a case report.

    PubMed

    Abdulcadir, Jasmine; Irion, Olivier; de Tejada, Begoña Martinez

    2015-12-01

    Nontherapeutic female genital modifications can cause short- and long-term consequences. Caregivers should promote women's self knowledge on genitals' anatomy and physiology, and psychophysical and sexual health. They should also inform on possible negative consequences of vulvar nontherapeutic alterations requested and avoid the medicalization of female genital mutilation.

  15. Considerations in the analysis and treatment of dietary effects on behavior: a case study.

    PubMed

    Bird, B L; Russo, D C; Cataldo, M F

    1977-12-01

    Scientific and public interest in the effects of diet of behavior disorders has recently increased. This paper argues that (1) the experimental analysis of behavior offers an effective scientific methodology for assessing the effects of dietary substances on behavior problems, and that (2) such analysis permits behavioral consequences to be considered as an alternative treatment to dietary control. A case study of a 9-year-old retarded boy with autistic behaviors is presented. Suspected dietary substances were demonstrated to be effective influences on the child's behavior, whereas a simple behavior modification program improved his problem behaviors. Also discussed are issues and problems which arise in research on dietary effects on behavior and in selection of effective and ethical treatments.

  16. {sub qT} uncertainties for W and Z production.

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

    Berge, S.; Nadolsky, P. M.; Olness, F. I.

    Analysis of semi-inclusive DIS hadroproduction suggests broadening of transverse momentum distributions at small x below 10-3 {approx} 10-2, which can be modeled in the Collins-Soper-Sterman formalism by a modification of impact parameter dependent parton densities. We investigate these consequences for the production of electroweak bosons at the Tevatron and the LHC. If substantial small-x broadening is observed in forward Z0 boson production in the Tevatron Run-2, it will strongly affect the predicted qT distributions for W{+-} and Z0 boson production at the LHC.

  17. Independent highly sensitive characterization of asparagine deamidation and aspartic acid isomerization by sheathless CZE-ESI-MS/MS.

    PubMed

    Gahoual, Rabah; Beck, Alain; François, Yannis-Nicolas; Leize-Wagner, Emmanuelle

    2016-02-01

    Amino acids residues are commonly submitted to various physicochemical modifications occurring at physiological pH and temperature. Post-translational modifications (PTMs) require comprehensive characterization because of their major influence on protein structure and involvement in numerous in vivo process or signaling. Mass spectrometry (MS) has gradually become an analytical tool of choice to characterize PTMs; however, some modifications are still challenging because of sample faint modification levels or difficulty to separate an intact peptide from modified counterparts before their transfer to the ionization source. Here, we report the implementation of capillary zone electrophoresis coupled to electrospray ionization tandem mass spectrometry (CZE-ESI-MS/MS) by the intermediate of a sheathless interfacing for independent and highly sensitive characterization of asparagine deamidation (deaN) and aspartic acid isomerization (isoD). CZE selectivity regarding deaN and isoD was studied extensively using different sets of synthetic peptides based on actual tryptic peptides. Results demonstrated CZE ability to separate the unmodified peptide from modified homologous exhibiting deaN, isoD or both independently with a resolution systematically superior to 1.29. Developed CZE-ESI-MS/MS method was applied for the characterization of monoclonal antibodies and complex protein mixture. Conserved CZE selectivity could be demonstrated even for complex samples, and foremost results obtained showed that CZE selectivity is similar regardless of the composition of the peptide. Separation of modified peptides prior to the MS analysis allowed to characterize and estimate modification levels of the sample independently for deaN and isoD even for peptides affected by both modifications and, as a consequence, enables to distinguish the formation of l-aspartic acid or d-aspartic acid generated from deaN. Separation based on peptide modification allowed, as supported by the ESI efficiency provided by CZE-ESI-MS/MS properties, and enabled to characterize and estimate studied PTMs with an unprecedented sensitivity and proved the relevance of implementing an electrophoretic driven separation for MS-based peptide analysis. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Poly(dimethyl siloxane) surface modification with biosurfactants isolated from probiotic strains.

    PubMed

    Pinto, S; Alves, P; Santos, A C; Matos, C M; Oliveiros, B; Gonçalves, S; Gudiña, E; Rodrigues, L R; Teixeira, J A; Gil, M H

    2011-09-15

    Depending on the final application envisaged for a given biomaterial, many surfaces must be modified before use. The material performance in a biological environment is mainly mediated by its surface properties that can be improved using suitable modification methods. The aim of this work was to coat poly(dimethyl siloxane) (PDMS) surfaces with biosurfactants (BSs) and to evaluate how these compounds affect the PDMS surface properties. BSs isolated from four probiotic strains (Lactococcus lactis, Lactobacillus paracasei, Streptococcus thermophilus A, and Streptococcus thermophilus B) were used. Bare PDMS and PDMS coated with BSs were characterized by contact angle measurements, infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The influence of the surface modifications on the materials blood compatibility was studied through thrombosis and hemolysis assays. The cytotoxicity of these materials was tested against rat peritoneal macrophages. AFM results demonstrated the successful coating of the surfaces. Also, by contact angle measurements, an increase of the coated surfaces hydrophilicity was seen. Furthermore, XPS analysis indicated a decrease of the silicon content at the surface, and ATR-FTIR results showed the presence of BS characteristic groups as a consequence of the modification. All the studied materials revealed no toxicity and were found to be nonhemolytic. The proposed approach for the modification of PDMS surfaces was found to be effective and opens new possibilities for the application of these surfaces in the biomedical field. Copyright © 2011 Wiley Periodicals, Inc.

  19. Superhydrophobic, Hybrid, Electrospun Cellulose Acetate Nanofibrous Mats for Oil/Water Separation by Tailored Surface Modification.

    PubMed

    Arslan, Osman; Aytac, Zeynep; Uyar, Tamer

    2016-08-03

    Electrospun cellulose acetate nanofibers (CA-NF) have been modified with perfluoro alkoxysilanes (FS/CA-NF) for tailoring their chemical and physical features aiming oil-water separation purposes. Strikingly, hybrid FS/CA-NF showed that perfluoro groups are rigidly positioned on the outer surface of the nanofibers providing superhydrophobic characteristic with a water contact angle of ∼155°. Detailed analysis showed that hydrolysis/condensation reactions led to the modification of the acetylated β(1 → 4) linked d-glucose chains of CA transforming it into a superhydrophobic nanofibrous mat. Analytical data have revealed that CA-NF surfaces can be selectively controlled for fabricating the durable, robust and water resistant hybrid electrospun nanofibrous mat. The -OH groups available on the CA structure allowed the basic sol-gel reactions started by the reactive FS hybrid precursor system which can be monitored by spectroscopic analysis. Since alkoxysilane groups on the perfluoro silane compound are capable of reacting for condensation together with the CA, superhydrophobic nanofibrous mat is obtained via electrospinning. This structural modification led to the facile fabrication of the novel oil/water nanofibrous separator which functions effectively demonstrated by hexane/oil and water separation experiments. Perfluoro groups consequently modified the hydrophilic CA nanofibers into superhydrophobic character and therefore FS/CA-NF could be quite practical for future applications like water/oil separators, as well as self-cleaning or water resistant nanofibrous structures.

  20. Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series).

    PubMed

    Loscalzo, Joseph; Handy, Diane E

    2014-06-01

    Epigenetics refers to heritable traits that are not a consequence of DNA sequence. Three classes of epigenetic regulation exist: DNA methylation, histone modification, and noncoding RNA action. In the cardiovascular system, epigenetic regulation affects development, differentiation, and disease propensity or expression. Defining the determinants of epigenetic regulation offers opportunities for novel strategies for disease prevention and treatment.

  1. [Genotoxic modification of nucleic acid bases and biological consequences of it. Review and prospects of experimental and computational investigations

    NASA Technical Reports Server (NTRS)

    Poltev, V. I.; Bruskov, V. I.; Shuliupina, N. V.; Rein, R.; Shibata, M.; Ornstein, R.; Miller, J.

    1993-01-01

    The review is presented of experimental and computational data on the influence of genotoxic modification of bases (deamination, alkylation, oxidation) on the structure and biological functioning of nucleic acids. Pathways are discussed for the influence of modification on coding properties of bases, on possible errors of nucleic acid biosynthesis, and on configurations of nucleotide mispairs. The atomic structure of nucleic acid fragments with modified bases and the role of base damages in mutagenesis and carcinogenesis are considered.

  2. Modification of a cyclo-olefin surface by radio-sterilization: is there any effect on the interaction with drug solutions?

    PubMed

    Barakat, Hala; Saunier, Johanna; Aymes Chodur, Caroline; Aubert, Pascal; Vigneron, Jackie; Etcheberry, Arnaud; Yagoubi, Najet

    2013-11-01

    A cyclo-olefin copolymer was subjected to an e-beam ionizing treatment. Two doses were studied: one corresponding to the recommended dose for the sterilization of pharmaceutical packaging (25 kGy), and a greater one to enhance the modifications caused by the treatment (150 kGy). The surface modifications were studied by X-ray photoelectron spectroscopy (XPS), contact angle measurements and atomic force microscopy (AFM). The roughness and the wettability of the surface were enhanced by the treatment. The consequences of the surface modifications on the drug interaction with the polymer were studied. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Drug Addiction and DNA Modifications.

    PubMed

    Brown, Amber N; Feng, Jian

    2017-01-01

    Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns. Understanding these epigenetic changes may provide us translational tools for the diagnosis and treatment of addiction in the future.

  4. Natural mixing of species: novel plant–animal communities on Caribbean Islands

    Treesearch

    Ariel E. Lugo; T.A. Carlo; Jr. Wunderle

    2012-01-01

    Global anthropogenic activities are responsible for the modification of landscapes, creation of novel environments and movement of species across biogeographic regions. A consequence of this activity is the mixing of native and introduced species and the formation of novel biotic communities. We review the ecological consequences of the mixing of native and introduced...

  5. Implementing the Recent Curricular Changes to English Language Instruction in Turkey: Opinions and Concerns of Elementary School Administrators

    ERIC Educational Resources Information Center

    Çelik, Servet; Kasapoðlu, Hülya

    2014-01-01

    Recent modifications to the Turkish educational system have mandated that instruction in English begin in the 2nd grade, rather than the 4th grade, as was previously required. Consequently, substantial modification of the elementary (2nd through 8th grade) English language teaching program has been carried out in order to accommodate this change.…

  6. [The action of high-molecular linear polymers on the circulatory system].

    PubMed

    Grigorian, S S; Sokolova, I A; Shakhnazarov, A A

    1995-01-01

    An analysis of the hemodynamic consequences of the injections of long linear polymers with high molecular weight is introduced. These injections lead to an increase of the cardiac output, to a decrease of the blood pressure, and hence cause a reduction of the resistance to blood flow. It follows that such kind of polymers is able to normalize hemodynamics under some pathophysiological conditions, e.g., during experimental atherosclerosis, ischemic state, hemorrhagic shock. An addition of drag-reducing polymers into the blood system is associated with a modification of the blood flow microstructure itself.

  7. Theory Creation, Modification, and Testing: An Information-Processing Model and Theory of the Anticipated and Unanticipated Consequences of Research and Development

    ERIC Educational Resources Information Center

    Perla, Rocco J.; Carifio, James

    2011-01-01

    Background: Extending Merton's (1936) work on the consequences of purposive social action, the model, theory and taxonomy outlined here incorporates and formalizes both anticipated and unanticipated research findings in a unified theoretical framework. The model of anticipated research findings was developed initially by Carifio (1975, 1977) and…

  8. Gender Affirmation and Body Modification Among Transgender Persons in Bogotá, Colombia.

    PubMed

    Aguayo-Romero, Rodrigo A; Reisen, Carol A; Zea, Maria Cecilia; Bianchi, Fernanda T; Poppen, Paul J

    This paper examined structural, social, and personal characteristics that shape the processes of gender affirmation and body modification among transgender persons (assigned male at birth) in Bogotá, Colombia. Qualitative data from life-history interviews (N=14) and a focus group (N=11) explored research questions concerning the ways in which the internal psychological and external contextual processes influence individuals' decisions and behaviors concerning hormonal treatment, injections, or surgery. Research questions concerning practices and consequences of treatment performed without medical supervision were addressed through qualitative data, as well as quantitative data from 58 transgender participants. Findings indicated variation in ways participants conceptualized gender (e.g., binary or fluid), but an increased feminine presentation was a strong personal desire expressed by many and often encouraged by romantic partners and transgender friends. Transgender individuals within participants' social networks were frequently instrumental not only in providing information about hormones and contouring injections, but also in carrying out procedures-sometimes with negative consequences. Body modification procedures occurred primarily outside the health care system, due to limited access to or awareness of medical care, societal stigma, social norms within the transgender community, and personal decision-making. Public health approaches to protect the health of transgender persons undergoing body modification were suggested.

  9. Gender Affirmation and Body Modification Among Transgender Persons in Bogotá, Colombia

    PubMed Central

    Aguayo-Romero, Rodrigo A.; Reisen, Carol A.; Zea, Maria Cecilia; Bianchi, Fernanda T.; Poppen, Paul J.

    2016-01-01

    This paper examined structural, social, and personal characteristics that shape the processes of gender affirmation and body modification among transgender persons (assigned male at birth) in Bogotá, Colombia. Qualitative data from life-history interviews (N=14) and a focus group (N=11) explored research questions concerning the ways in which the internal psychological and external contextual processes influence individuals' decisions and behaviors concerning hormonal treatment, injections, or surgery. Research questions concerning practices and consequences of treatment performed without medical supervision were addressed through qualitative data, as well as quantitative data from 58 transgender participants. Findings indicated variation in ways participants conceptualized gender (e.g., binary or fluid), but an increased feminine presentation was a strong personal desire expressed by many and often encouraged by romantic partners and transgender friends. Transgender individuals within participants' social networks were frequently instrumental not only in providing information about hormones and contouring injections, but also in carrying out procedures—sometimes with negative consequences. Body modification procedures occurred primarily outside the health care system, due to limited access to or awareness of medical care, societal stigma, social norms within the transgender community, and personal decision-making. Public health approaches to protect the health of transgender persons undergoing body modification were suggested. PMID:26839525

  10. A Generalizable Platform for Interrogating Target- and Signal-Specific Consequences of Electrophilic Modifications in Redox-Dependent Cell Signaling

    PubMed Central

    Lin, Hong-Yu; Haegele, Joseph A.; Disare, Michael T.; Lin, Qishan; Aye, Yimon

    2015-01-01

    Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized “electrophile toolbox” with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology—T-REX (targetable reactive electrophiles & oxidants)—is established by: (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein—one of several redox-sensitive regulators of the Nrf2–ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2–ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background. PMID:25909755

  11. A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

    PubMed

    Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

    2015-05-20

    Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

  12. Consequences of additional use of PET information for target volume delineation and radiotherapy dose distribution for esophageal cancer.

    PubMed

    Muijs, Christina T; Schreurs, Liesbeth M; Busz, Dianne M; Beukema, Jannet C; van der Borden, Arnout J; Pruim, Jan; Van der Jagt, Eric J; Plukker, John Th; Langendijk, Johannes A

    2009-12-01

    To determine the consequences of target volume (TV) modifications, based on the additional use of PET information, on radiation planning, assuming PET/CT-imaging represents the true extent of the tumour. For 21 patients with esophageal cancer, two separate TV's were retrospectively defined based on CT (CT-TV) and co-registered PET/CT images (PET/CT-TV). Two 3D-CRT plans (prescribed dose 50.4 Gy) were constructed to cover the corresponding TV's. Subsequently, these plans were compared for target coverage, normal tissue dose-volume histograms and the corresponding normal tissue complication probability (NTCP) values. The addition of PET led to the modification of CT-TV with at least 10% in 12 of 21 patients (57%) (reduction in 9, enlargement in 3). PET/CT-TV was inadequately covered by the CT-based treatment plan in 8 patients (36%). Treatment plan modifications resulted in significant changes (p<0.05) in dose distributions to heart and lungs. Corresponding changes in NTCP values ranged from -3% to +2% for radiation pneumonitis and from -0.2% to +1.2% for cardiac mortality. This study demonstrated that TV's based on CT might exclude PET-avid disease. Consequences are under dosing and thereby possibly ineffective treatment. Moreover, the addition of PET in radiation planning might result in clinical important changes in NTCP.

  13. Exploring the perception of nursing students about consequences of reflection in clinical settings

    PubMed Central

    Karimi, Shahnaz; Haghani, Fariba; Yamani, Nikoo; Kalyani, Majid Najafi

    2017-01-01

    Background Reflection on practical experiences is a key element that enables students to recognize their own strengths and weaknesses and develop nursing skills. Whilst reflection may enhance students’ learning in practice, there is little evidence about nursing students’ perception of the consequences of reflection in clinical settings. Objective This study aimed to explore Iranian nursing students’ perception regarding the consequences of reflection during clinical practices. Methods This qualitative study was conducted by a conventional content analysis approach in two nursing schools at Shiraz and Fasa Universities of Medical Sciences in Iran. Data were collected through in-depth semi-structured interviews during 2015–2016, from 20 students selected by purposive sampling. All the interviews were tape-recorded, transcribed verbatim, and analyzed by content analysis method. Rigor of this study was approved by member check and external audit. Results Two categories emerged from the data analysis, including movement toward professionalism and self-actualization of emotions. The former consisted of three subcategories of function modification, sharing experiences and generalizing experiences. The latter consisted of two subcategories of inner satisfaction and peace of mind. Conclusion The results indicated that nursing students’ reflection in clinical settings is effective in personal and professional levels. Reflection in a personal level led to positive emotions that increased the quality of care in patients. Accordingly, nursing educators need to create a nurturing climate as well as supporting reflective behaviors of nursing students. PMID:29038696

  14. Increase in the Hydrophilicity and Lewis Acid-Base Properties of Solid Surfaces Achieved by Electric Gliding Discharge in Humid Air: Effects on Bacterial Adherence

    NASA Astrophysics Data System (ADS)

    Kamgang, J. O.; Naitali, M.; Herry, J.-M.; Bellon-Fontaine, M.-N.; Brisset, J.-L.; Briandet, R.

    2009-04-01

    This study addressed the effects of treatment with gliding discharge plasma on the surface properties of solid materials, as well as the consequences concerning adherence of a model bacterium. As evaluated by contact angles with selected liquids, plasma treatment caused an increase in surface hydrophilicity and in the Lewis acid-base components of the surface energy of all materials tested. These modifications were more marked for low density polyethylene and stainless steel than for polytetrafluoroethylene. After treatment, the hydrophilicity of the materials remained relatively stable for at least 20 days. Moreover, analysis of the topography of the materials by atomic force microscopy revealed that the roughness of both polymers was reduced by glidarc plasma treatment. As a result of all these modifications, solid substrates were activated towards micro-organisms and the adherence of S. epidermidis, a negatively charged Lewis-base and mildly hydrophilic strain selected as the model, was increased in almost all the cases tested.

  15. Effect of Terminal Modification on the Molecular Assembly and Mechanical Properties of Protein-Based Block Copolymers.

    PubMed

    Jacobsen, Matthew M; Tokareva, Olena S; Ebrahimi, Davoud; Huang, Wenwen; Ling, Shengjie; Dinjaski, Nina; Li, David; Simon, Marc; Staii, Cristian; Buehler, Markus J; Kaplan, David L; Wong, Joyce Y

    2017-09-01

    Accurate prediction and validation of the assembly of bioinspired peptide sequences into fibers with defined mechanical characteristics would aid significantly in designing and creating materials with desired properties. This process may also be utilized to provide insight into how the molecular architecture of many natural protein fibers is assembled. In this work, computational modeling and experimentation are used in tandem to determine how peptide terminal modification affects a fiber-forming core domain. Modeling shows that increased terminal molecular weight and hydrophilicity improve peptide chain alignment under shearing conditions and promote consolidation of semicrystalline domains. Mechanical analysis shows acute improvements to strength and elasticity, but significantly reduced extensibility and overall toughness. These results highlight an important entropic function that terminal domains of fiber-forming peptides exhibit as chain alignment promoters, which ultimately has notable consequences on the mechanical behavior of the final fiber products. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Agm1/Pgm3-Mediated Sugar Nucleotide Synthesis Is Essential for Hematopoiesis and Development▿

    PubMed Central

    Greig, Kylie T.; Antonchuk, Jennifer; Metcalf, Donald; Morgan, Phillip O.; Krebs, Danielle L.; Zhang, Jian-Guo; Hacking, Douglas F.; Bode, Lars; Robb, Lorraine; Kranz, Christian; de Graaf, Carolyn; Bahlo, Melanie; Nicola, Nicos A.; Nutt, Stephen L.; Freeze, Hudson H.; Alexander, Warren S.; Hilton, Douglas J.; Kile, Benjamin T.

    2007-01-01

    Carbohydrate modification of proteins includes N-linked and O-linked glycosylation, proteoglycan formation, glycosylphosphatidylinositol anchor synthesis, and O-GlcNAc modification. Each of these modifications requires the sugar nucleotide UDP-GlcNAc, which is produced via the hexosamine biosynthesis pathway. A key step in this pathway is the interconversion of GlcNAc-6-phosphate (GlcNAc-6-P) and GlcNAc-1-P, catalyzed by phosphoglucomutase 3 (Pgm3). In this paper, we describe two hypomorphic alleles of mouse Pgm3 and show there are specific physiological consequences of a graded reduction in Pgm3 activity and global UDP-GlcNAc levels. Whereas mice lacking Pgm3 die prior to implantation, animals with less severe reductions in enzyme activity are sterile, exhibit changes in pancreatic architecture, and are anemic, leukopenic, and thrombocytopenic. These phenotypes are accompanied by specific rather than wholesale changes in protein glycosylation, suggesting that while universally required, the functions of certain proteins and, as a consequence, certain cell types are especially sensitive to reductions in Pgm3 activity. PMID:17548465

  17. Characterization of Cell Wall Components and Their Modifications during Postharvest Storage of Asparagus officinalis L.: Storage-Related Changes in Dietary Fiber Composition.

    PubMed

    Schäfer, Judith; Wagner, Steffen; Trierweiler, Bernhard; Bunzel, Mirko

    2016-01-20

    Changes in cell wall composition during storage of plant foods potentially alter the physiological effects of dietary fiber components. To investigate postharvest cell wall modifications of asparagus and their consequences in terms of insoluble dietary fiber structures, asparagus was stored at 20 and 1 °C for different periods of time. Structural analyses demonstrated postharvest changes in the polysaccharide profile, dominated by decreased portions of galactans. Increasing lignin contents correlated with compositional changes (monolignol ratios and linkage types) of the lignin polymer as demonstrated by chemical and two-dimensional nuclear magnetic resonance (2D-NMR) methods. Depending on the storage time and temperature, syringyl units were preferentially incorporated into the lignin polymer. Furthermore, a drastic increase in the level of ester-linked phenolic monomers (i.e., p-coumaric acid and ferulic acid) and polymer cross-links (di- and triferulic acids) was detected. The attachment of p-coumaric acid to lignin was demonstrated by 2D-NMR experiments. Potential consequences of postharvest modifications on physiological effects of asparagus dietary fiber are discussed.

  18. S-Nitrosylation: Specificity, Occupancy, and Interaction with Other Post-Translational Modifications

    PubMed Central

    Kohr, Mark J.; Murphy, Elizabeth

    2013-01-01

    Abstract Significance: S-nitrosylation (SNO) has been identified throughout the body as an important signaling modification both in physiology and a variety of diseases. SNO is a multifaceted post-translational modification, in that it can either act as a signaling molecule itself or as an intermediate to other modifications. Recent Advances and Critical Issues: Through extensive SNO research, we have made progress toward understanding the importance of single cysteine-SNO sites; however, we are just beginning to explore the importance of specific SNO within the context of other SNO sites and post-translational modifications. Additionally, compartmentalization and SNO occupancy may play an important role in the consequences of the SNO modification. Future Directions: In this review, we will consider the context of SNO signaling and discuss how the transient nature of SNO, its role as an oxidative intermediate, and the pattern of SNO, should be considered when determining the impact of SNO signaling. Antioxid. Redox Signal. 19, 1209–1219. PMID:23157187

  19. T-REX on-demand redox targeting in live cells.

    PubMed

    Parvez, Saba; Long, Marcus J C; Lin, Hong-Yu; Zhao, Yi; Haegele, Joseph A; Pham, Vanha N; Lee, Dustin K; Aye, Yimon

    2016-12-01

    This protocol describes targetable reactive electrophiles and oxidants (T-REX)-a live-cell-based tool designed to (i) interrogate the consequences of specific and time-resolved redox events, and (ii) screen for bona fide redox-sensor targets. A small-molecule toolset comprising photocaged precursors to specific reactive redox signals is constructed such that these inert precursors specifically and irreversibly tag any HaloTag-fused protein of interest (POI) in mammalian and Escherichia coli cells. Syntheses of the alkyne-functionalized endogenous reactive signal 4-hydroxynonenal (HNE(alkyne)) and the HaloTag-targetable photocaged precursor to HNE(alkyne) (also known as Ht-PreHNE or HtPHA) are described. Low-energy light prompts photo-uncaging (t 1/2 <1-2 min) and target-specific modification. The targeted modification of the POI enables precisely timed and spatially controlled redox events with no off-target modification. Two independent pathways are described, along with a simple setup to functionally validate known targets or discover novel sensors. T-REX sidesteps mixed responses caused by uncontrolled whole-cell swamping with reactive signals. Modification and downstream response can be analyzed by in-gel fluorescence, proteomics, qRT-PCR, immunofluorescence, fluorescence resonance energy transfer (FRET)-based and dual-luciferase reporters, or flow cytometry assays. T-REX targeting takes 4 h from initial probe treatment. Analysis of targeted redox responses takes an additional 4-24 h, depending on the nature of the pathway and the type of readouts used.

  20. T-REX on-demand redox targeting in live cells

    PubMed Central

    Parvez, Saba; Long, Marcus J C; Lin, Hong-Yu; Zhao, Yi; Haegele, Joseph A; Pham, Vanha N; Lee, Dustin K; Aye, Yimon

    2017-01-01

    This protocol describes targetable reactive electrophiles and oxidants (T-REX)—a live-cell-based tool designed to (i) interrogate the consequences of specific and time-resolved redox events, and (ii) screen for bona fide redox-sensor targets. A small-molecule toolset comprising photocaged precursors to specific reactive redox signals is constructed such that these inert precursors specifically and irreversibly tag any HaloTag-fused protein of interest (POI) in mammalian and Escherichia coli cells. Syntheses of the alkyne-functionalized endogenous reactive signal 4-hydroxynonenal (HNE (alkyne)) and the HaloTag-targetable photocaged precursor to HNE (alkyne) (also known as Ht-PreHNE or HtPHA) are described. Low-energy light prompts photo-uncaging (t1/2 <1–2 min) and target-specific modification. The targeted modification of the POI enables precisely timed and spatially controlled redox events with no off-target modification. Two independent pathways are described, along with a simple setup to functionally validate known targets or discover novel sensors. T-REX sidesteps mixed responses caused by uncontrolled whole-cell swamping with reactive signals. Modification and downstream response can be analyzed by in-gel fluorescence, proteomics, qRT-PCR, immunofluorescence, fluorescence resonance energy transfer (FRET)-based and dual-luciferase reporters, or flow cytometry assays. T-REX targeting takes 4 h from initial probe treatment. Analysis of targeted redox responses takes an additional 4–24 h, depending on the nature of the pathway and the type of readouts used. PMID:27809314

  1. Progress of targeted genome modification approaches in higher plants.

    PubMed

    Cardi, Teodoro; Neal Stewart, C

    2016-07-01

    Transgene integration in plants is based on illegitimate recombination between non-homologous sequences. The low control of integration site and number of (trans/cis)gene copies might have negative consequences on the expression of transferred genes and their insertion within endogenous coding sequences. The first experiments conducted to use precise homologous recombination for gene integration commenced soon after the first demonstration that transgenic plants could be produced. Modern transgene targeting categories used in plant biology are: (a) homologous recombination-dependent gene targeting; (b) recombinase-mediated site-specific gene integration; (c) oligonucleotide-directed mutagenesis; (d) nuclease-mediated site-specific genome modifications. New tools enable precise gene replacement or stacking with exogenous sequences and targeted mutagenesis of endogeneous sequences. The possibility to engineer chimeric designer nucleases, which are able to target virtually any genomic site, and use them for inducing double-strand breaks in host DNA create new opportunities for both applied plant breeding and functional genomics. CRISPR is the most recent technology available for precise genome editing. Its rapid adoption in biological research is based on its inherent simplicity and efficacy. Its utilization, however, depends on available sequence information, especially for genome-wide analysis. We will review the approaches used for genome modification, specifically those for affecting gene integration and modification in higher plants. For each approach, the advantages and limitations will be noted. We also will speculate on how their actual commercial development and implementation in plant breeding will be affected by governmental regulations.

  2. Epigenetics Mechanisms in Alzheimer’s disease

    PubMed Central

    Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul D.; Rogers, Joseph

    2011-01-01

    Epigenetic modifications help orchestrate sweeping developmental, aging, and disease-causing changes in phenotype by altering transcriptional activity in multiple genes spanning multiple biologic pathways. Although previous epigenetic research has focused primarily on dividing cells, particularly in cancer, recent studies have shown rapid, dynamic, and persistent epigenetic modifications in neurons that have significant neuroendocrine, neurophysiologic, and neurodegenerative consequences. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and Alzheimer’s disease (AD). Because of their reach across the genome, epigenetic mechanisms may provide a unique integrative framework for the pathologic diversity and complexity of AD. PMID:21482442

  3. Understanding the structural and dynamic consequences of DNA epigenetic modifications: Computational insights into cytosine methylation and hydroxymethylation

    PubMed Central

    Carvalho, Alexandra T P; Gouveia, Leonor; Kanna, Charan Raju; Wärmländer, Sebastian K T S; Platts, Jamie A; Kamerlin, Shina Caroline Lynn

    2014-01-01

    We report a series of molecular dynamics (MD) simulations of up to a microsecond combined simulation time designed to probe epigenetically modified DNA sequences. More specifically, by monitoring the effects of methylation and hydroxymethylation of cytosine in different DNA sequences, we show, for the first time, that DNA epigenetic modifications change the molecule's dynamical landscape, increasing the propensity of DNA toward different values of twist and/or roll/tilt angles (in relation to the unmodified DNA) at the modification sites. Moreover, both the extent and position of different modifications have significant effects on the amount of structural variation observed. We propose that these conformational differences, which are dependent on the sequence environment, can provide specificity for protein binding. PMID:25625845

  4. Nonenzymatic glycation of guanosine 5'-triphosphate by glyceraldehyde: an in vitro study of AGE formation.

    PubMed

    Li, Yuyuan; Dutta, Udayan; Cohenford, Menashi A; Dain, Joel A

    2007-12-01

    Guanosine 5'-triphosphate (GTP) plays a significant role in the bioenergetics, metabolism, and signaling of cells; consequently, any modifications to the structure of the molecule can have profound effects on a cell's survival and function. Previous studies in our laboratory demonstrated that like proteins, purines, and pyrimidines can nonenzymatically react with sugars to generate advanced glycation endproducts (AGEs) and that these AGEs can form in vitro under physiological conditions. The objective of this investigation was twofold. First, it was to evaluate the susceptibility of ATP, GTP, CTP, and TTP to nonenzymatic modification by D-glucose and DL-glyceraldehyde, and second to assess the effect of various factors such as temperature, pH and incubation time, and sugar concentration on the rate and extent of nucleotide triphosphate AGE formation. Of the four nucleotide triphosphates that were studied, only GTP was significantly reactive forming a heterogeneous group of compounds with DL-glyceraldehyde. D-Glucose exhibited no significant reactivity with any of the nucleotide triphosphates, a finding that was supported by UV and fluorescence spectroscopy. Capillary electrophoresis, high-performance liquid chromatography and mass spectrometry allowed for a thorough analysis of the glycated GTP products and demonstrated that the modification of GTP by dl-glyceraldehyde occurred via the classical Amadori pathway.

  5. Orthorhombic-tetragonal phase coexistence and enhanced piezo-response at room temperature in Zr, Sn, and Hf modified BaTiO{sub 3}

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

    Kalyani, Ajay Kumar; Brajesh, Kumar; Ranjan, Rajeev, E-mail: rajeev@materials.iisc.ernet.in

    2014-06-23

    The effect of Zr, Hf, and Sn in BaTiO{sub 3} has been investigated at close composition intervals in the dilute concentration limit. Detailed structural analysis by x-ray and neutron powder diffraction revealed that merely 2 mol. % of Zr, Sn, and Hf stabilizes a coexistence of orthorhombic (Amm2) and tetragonal (P4mm) phases at room temperature. As a consequence, all the three systems show substantial enhancement in the longitudinal piezoelectric coefficient (d{sub 33}), with Sn modification exhibiting the highest value ∼425 pC/N.

  6. Global change: Geographical approaches (A Review)*

    PubMed Central

    Kotlyakov, V. M.; Mather, J. R.; Sdasyuk, G. V.; White, G. F.

    1988-01-01

    The International Geosphere Biosphere Program sponsored by the International Council of Scientific Unions is directing attention to geophysical and biological change as influenced by human modifications in global energy and mass exchanges. Geographers in the Soviet Union and the United States have joined in critical appraisal of their experience in studying environmental change. This initial report is on some promising approaches, such as the reconstruction of earlier landscape processes, modeling of the dynamics of present-day landscapes, analysis of causes and consequences of anthropogenic changes in specified regions, appraisal of social response to change, and enhanced geographic information systems supported by detailed site studies. PMID:16593971

  7. Photothermal Radiometry and Diffuse Reflectance Analysis of Thermally Treated Bones

    NASA Astrophysics Data System (ADS)

    Trujillo, S.; Martínez-Torres, P.; Quintana, P.; Alvarado-Gil, Juan Jose

    2010-05-01

    Different fields such as archaeology, biomedicine, forensic science, and pathology involve the analysis of burned bones. In this work, the effects of successive thermal treatments on pig long bones, measured by photothermal radiometry and diffuse reflectance are reported. Measurements were complemented by X-ray diffraction and infrared spectroscopy. Samples were thermally treated for 1 h within the range of 25 °C to 350 °C. The thermal diffusivity and reflectance increase in the low-temperature range, reaching a maximum around 125 °C and decaying at higher temperatures. These results are the consequence of complex modifications occurring in the inorganic and organic bone structure. For lower temperatures dehydration, dehydroxilation, and carbonate loss processes are dominant, followed by collagen denaturing and decompositions, which have an influence on the bone microstructure.

  8. Derivatizing weak polyelectrolytes--solution properties, self-aggregation, and association with anionic surfaces of hydrophobically modified poly(ethylene imine).

    PubMed

    Griffiths, Peter C; Paul, Alison; Fallis, Ian A; Wellappili, Champa; Murphy, Damien M; Jenkins, Robert; Waters, Sarah J; Nilmini, Renuka; Heenan, Richard K; King, Stephen M

    2007-10-15

    The physical properties of weak polyelectrolytes may be tailored via hydrophobic modification to exhibit useful properties under appropriate pH and ionic strength conditions as a consequence of the often inherently competing effects of electrostatics and hydrophobicity. Pulsed-gradient spin-echo NMR (PGSE-NMR), electron paramagnetic resonance (EPR), small-angle neutron scattering (SANS) surface tension, fluorescence, and pH titration have been used to examine the solution conformation and aggregation behavior of a series of hydrophobically modified hyperbranched poly(ethylene imine) (PEI) polymers in aqueous solution, and their interaction with sodium dodecylsulfate (SDS). PGSE-NMR gave a particularly insightful picture of the apparent molecular weight distribution. The presence of the hydrophobes led to a lower effective charge on the polymer at any given pH, compared to the (parent) nonmodified samples. Analysis of the SANS data showed that the propensity to form highly elliptical or rod-like aggregates at higher pHs, reflecting both the changes in protonation behavior induced by the hydrophobic modification and an hydrophobic interaction, but that these structures were disrupted with decreasing pH (increasing charge). The parent samples were not surface active yet the hydrophobically modified samples show pronounced surface activity and the presence of small hydrophobic domains. The surface activity increased with an increase in the degree of modification. On addition of SDS, the onset of the formation of polymer/surfactant complexes was insensitive to the degree of modification with the resultant PEI/SDS complexes resembling the size and shape of simple SDS micelles. Indeed, the presence of the SDS effectively nullifies the effects of the hydrophobe. Hydrophobic modification is therefore a viable option to tailor pH dependent properties, whose effects may be removed by the presence of surfactant.

  9. Where systems biology meets postharvest

    USDA-ARS?s Scientific Manuscript database

    Interpreting fruit metabolism, particularly tree fruit metabolism, presents unique challenges. Long periods from tree establishment to fruiting render techniques directed towards reducing the complexity of metabolic mechanisms, such as genomic modification, relatively difficult. Consequently, holi...

  10. Tripping Up Trp: Modification of Protein Tryptophan Residues by Reactive Oxygen Species, Modes of Detection, and Biological Consequences

    PubMed Central

    Ehrenshaft, Marilyn; Deterding, Leesa J.; Mason, Ronald P.

    2015-01-01

    Proteins comprise a majority of the dry weight of a cell, rendering them a major target for oxidative modification. Oxidation of proteins can result in significant alterations in protein molecular mass such as breakage of the polypeptide backbone, and/or polymerization of monomers into dimers, multimers and sometimes into insoluble aggregates. Protein oxidation can also result in structural changes to amino acid residue side chains, conversions which have only a modest effect on protein size but can have widespread consequences for protein function. There are a wide range of rate constants for amino acid reactivity, with cysteine, methionine, tyrosine, phenylalanine and tryptophan having the highest rate constants with commonly encountered biological oxidants. Free tryptophan and tryptophan protein residues react at a diffusion limited rate with hydroxyl radical, and also have high rate constants for reactions with singlet oxygen and ozone. Although oxidation of proteins in general and tryptophan residues specifically can have effects detrimental to the health of cells and organisms, some modifications are neutral while others contribute to the function of the protein in question or may act as a signal that damaged proteins need to be replaced. This review provides a brief overview of the chemical mechanisms by which tryptophan residues become oxidized, presents both the strengths and weaknesses of some of the techniques used to detect these oxidative interactions and discusses selected examples of the biological consequences of tryptophan oxidation in proteins from animals, plants and microbes. PMID:26393422

  11. An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

    PubMed Central

    Hook, MA; Grau, JW

    2011-01-01

    Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

  12. Protein tyrosine nitration in plants: Present knowledge, computational prediction and future perspectives.

    PubMed

    Kolbert, Zsuzsanna; Feigl, Gábor; Bordé, Ádám; Molnár, Árpád; Erdei, László

    2017-04-01

    Nitric oxide (NO) and related molecules (reactive nitrogen species) regulate diverse physiological processes mainly through posttranslational modifications such as protein tyrosine nitration (PTN). PTN is a covalent and specific modification of tyrosine (Tyr) residues resulting in altered protein structure and function. In the last decade, great efforts have been made to reveal candidate proteins, target Tyr residues and functional consequences of nitration in plants. This review intends to evaluate the accumulated knowledge about the biochemical mechanism, the structural and functional consequences and the selectivity of plants' protein nitration and also about the decomposition or conversion of nitrated proteins. At the same time, this review emphasizes yet unanswered or uncertain questions such as the reversibility/irreversibility of tyrosine nitration, the involvement of proteasomes in the removal of nitrated proteins or the effect of nitration on Tyr phosphorylation. The different NO producing systems of algae and higher plants raise the possibility of diversely regulated protein nitration. Therefore studying PTN from an evolutionary point of view would enrich our present understanding with novel aspects. Plant proteomic research can be promoted by the application of computational prediction tools such as GPS-YNO 2 and iNitro-Tyr software. Using the reference Arabidopsis proteome, Authors performed in silico analysis of tyrosine nitration in order to characterize plant tyrosine nitroproteome. Nevertheless, based on the common results of the present prediction and previous experiments the most likely nitrated proteins were selected thus recommending candidates for detailed future research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Functional Analysis of Problem Behavior: A Systematic Approach for Identifying Idiosyncratic Variables

    PubMed Central

    Roscoe, Eileen M.; Schlichenmeyer, Kevin J.; Dube, William V.

    2015-01-01

    When inconclusive functional analysis (FA) outcomes occur, a number of modifications have been made to enhance the putative establishing operation or consequence associated with behavioral maintenance. However, a systematic method for identifying relevant events to test during modified FAs has not been evaluated. The purpose of this study was to develop and evaluate a technology for systematically identifying events to test in a modified FA after an initial FA led to inconclusive outcomes. Six individuals whose initial FA showed little or no responding or high levels only in the control condition participated. An indirect assessment (IA) questionnaire developed for identifying idiosyncratic variables was administered, and a descriptive analysis (DA) was conducted. Results from the IA only or a combination of the IA and DA were used to inform modified FA test and control conditions. Conclusive FA outcomes were obtained with five of the six participants during the modified FA phase. PMID:25930176

  14. Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

    NASA Astrophysics Data System (ADS)

    Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

    2016-04-01

    Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

  15. Undermining and Strengthening Social Networks through Network Modification

    PubMed Central

    Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

    2016-01-01

    Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention. PMID:27703198

  16. Undermining and Strengthening Social Networks through Network Modification.

    PubMed

    Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

    2016-10-05

    Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention.

  17. Undermining and Strengthening Social Networks through Network Modification

    NASA Astrophysics Data System (ADS)

    Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

    2016-10-01

    Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention.

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

    Brock, T.D.

    Thermal pollution is discussed with regard to sources of manmade thermal water; thermal consequences of thermal pollution; and thermal effects on water quality. Natural habitats receiving thermal additions are discussed with regard to geothermal habitats and geothermal modification of normal aquatic ecosystems. Ecological observations on geothermal habitats include upper temperature limits for various taxonomic groups and consequences of species restriction by temperature. General ecological consequences of thermal polution are discussed with regard to differences between thermal effects on cold and warm water habitats; adaptation to the thermal environment; effect of temperature on gruwth rate; temperatare and water quality; and bacterialmore » indicators of thermal pollution. (HLW)« less

  19. Multiple performance measures are needed to evaluate triage systems in the emergency department.

    PubMed

    Zachariasse, Joany M; Nieboer, Daan; Oostenbrink, Rianne; Moll, Henriëtte A; Steyerberg, Ewout W

    2018-02-01

    Emergency department triage systems can be considered prediction rules with an ordinal outcome, where different directions of misclassification have different clinical consequences. We evaluated strategies to compare the performance of triage systems and aimed to propose a set of performance measures that should be used in future studies. We identified performance measures based on literature review and expert knowledge. Their properties are illustrated in a case study evaluating two triage modifications in a cohort of 14,485 pediatric emergency department visits. Strengths and weaknesses of the performance measures were systematically appraised. Commonly reported performance measures are measures of statistical association (34/60 studies) and diagnostic accuracy (17/60 studies). The case study illustrates that none of the performance measures fulfills all criteria for triage evaluation. Decision curves are the performance measures with the most attractive features but require dichotomization. In addition, paired diagnostic accuracy measures can be recommended for dichotomized analysis, and the triage-weighted kappa and Nagelkerke's R 2 for ordinal analyses. Other performance measures provide limited additional information. When comparing modifications of triage systems, decision curves and diagnostic accuracy measures should be used in a dichotomized analysis, and the triage-weighted kappa and Nagelkerke's R 2 in an ordinal approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Unintended Consequences of Wearable Sensor Use in Healthcare. Contribution of the IMIA Wearable Sensors in Healthcare WG.

    PubMed

    Schukat, M; McCaldin, D; Wang, K; Schreier, G; Lovell, N H; Marschollek, M; Redmond, S J

    2016-11-10

    As wearable sensors take the consumer market by storm, and medical device manufacturers move to make their devices wireless and appropriate for ambulatory use, this revolution brings with it some unintended consequences, which we aim to discuss in this paper. We discuss some important unintended consequences, both beneficial and unwanted, which relate to: modifications of behavior; creation and use of big data sets; new security vulnerabilities; and unforeseen challenges faced by regulatory authorities, struggling to keep pace with recent innovations. Where possible, we proposed potential solutions to unwanted consequences. Intelligent and inclusive design processes may mitigate unintended modifications in behavior. For big data, legislating access to and use of these data will be a legal and political challenge in the years ahead, as we trade the health benefits of wearable sensors against the risk to our privacy. The wireless and personal nature of wearable sensors also exposes them to a number of unique security vulnerabilities. Regulation plays an important role in managing these security risks, but also has the dual responsibility of ensuring that wearable devices are fit for purpose. However, the burden of validating the function and security of medical devices is becoming infeasible for regulators, given the many software apps and wearable sensors entering the market each year, which are only a subset of an even larger 'internet of things'. Wearable sensors may serve to improve wellbeing, but we must be vigilant against the occurrence of unintended consequences. With collaboration between device manufacturers, regulators, and end-users, we balance the risk of unintended consequences occurring against the incredible benefit that wearable sensors promise to bring to the world.

  1. Unintended Consequences of Wearable Sensor Use in Healthcare

    PubMed Central

    McCaldin, D.; Wang, K.; Schreier, G.; Lovell, N. H.; Marschollek, M.; Redmond, S. J.

    2016-01-01

    Summary Objectives As wearable sensors take the consumer market by storm, and medical device manufacturers move to make their devices wireless and appropriate for ambulatory use, this revolution brings with it some unintended consequences, which we aim to discuss in this paper. Methods We discuss some important unintended consequences, both beneficial and unwanted, which relate to: modifications of behavior; creation and use of big data sets; new security vulnerabilities; and unforeseen challenges faced by regulatory authorities, struggling to keep pace with recent innovations. Where possible, we proposed potential solutions to unwanted consequences. Results Intelligent and inclusive design processes may mitigate unintended modifications in behavior. For big data, legislating access to and use of these data will be a legal and political challenge in the years ahead, as we trade the health benefits of wearable sensors against the risk to our privacy. The wireless and personal nature of wearable sensors also exposes them to a number of unique security vulnerabilities. Regulation plays an important role in managing these security risks, but also has the dual responsibility of ensuring that wearable devices are fit for purpose. However, the burden of validating the function and security of medical devices is becoming infeasible for regulators, given the many software apps and wearable sensors entering the market each year, which are only a subset of an even larger ‘internet of things’. Conclusion Wearable sensors may serve to improve wellbeing, but we must be vigilant against the occurrence of unintended consequences. With collaboration between device manufacturers, regulators, and end-users, we balance the risk of unintended consequences occurring against the incredible benefit that wearable sensors promise to bring to the world. PMID:27830234

  2. Interpretation of the BRITE oscillation data of the hybrid pulsator ν Eridani: a call for the modification of stellar opacities

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

    Daszyńska-Daszkiewicz, J.; Pamyatnykh, A. A.; Walczak, P.

    The analysis of the BRIght Target Explorer (BRITE) oscillation spectrum of the main-sequence early B-type star ν Eridani is presented in this paper. Only models with the modified mean opacity profile can account for the observed frequency ranges as well as for the values of some individual frequencies. The number of the κ-modified seismic models is constrained by the non-adiabatic parameter f, which is very sensitive to the opacity changes in the subphotospheric layers, where the pulsations are driven. We present an example of the model that satisfies all the above conditions. It seems that the OPLIB opacities are preferredmore » over those from the OPAL and OP projects. Finally and moreover, we discuss additional consequences of the opacity modification, namely, an enhancement of the efficiency of convection in the Z bump as well as an occurrence of close radial modes which is a kind of avoided-crossing phenomenon common for non-radial modes in standard main-sequence models.« less

  3. Interpretation of the BRITE oscillation data of the hybrid pulsator ν Eridani: a call for the modification of stellar opacities

    DOE PAGES

    Daszyńska-Daszkiewicz, J.; Pamyatnykh, A. A.; Walczak, P.; ...

    2016-12-22

    The analysis of the BRIght Target Explorer (BRITE) oscillation spectrum of the main-sequence early B-type star ν Eridani is presented in this paper. Only models with the modified mean opacity profile can account for the observed frequency ranges as well as for the values of some individual frequencies. The number of the κ-modified seismic models is constrained by the non-adiabatic parameter f, which is very sensitive to the opacity changes in the subphotospheric layers, where the pulsations are driven. We present an example of the model that satisfies all the above conditions. It seems that the OPLIB opacities are preferredmore » over those from the OPAL and OP projects. Finally and moreover, we discuss additional consequences of the opacity modification, namely, an enhancement of the efficiency of convection in the Z bump as well as an occurrence of close radial modes which is a kind of avoided-crossing phenomenon common for non-radial modes in standard main-sequence models.« less

  4. Colonization and Disappearance of Mytilus galloprovincialisLam. on an Artificial Habitat in the Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Ardizzone, G. D.; Belluscio, A.; Gravina, M. F.; Somaschini, A.

    1996-12-01

    A Mytilus galloprovincialispopulation, settled on a new artificial habitat at 12 m depth in the Central Tyrrhenian Sea, was investigated for 10 years. The new substratum, located at a depth lower than the preferential range of the species, was colonized temporarily by mussels which reached very high densities and dominated the benthic community from their colonization until the third year. The length-frequency distribution analysis showed a progressively complex population structure with up to three cohorts. The yearly recruitments were observed once a year in spring. The growth curve provided a maximum length higher than that reported for shallow waters. Nevertheless, the gregarious habits of mussels and the reduced water movement caused edaphic modifications of the substratum, which was covered progressively by sediments and biodeposits (pseudofaeces). Consequently, the population structure was affected by a reduction of the newly recruited cohorts, and mussels disappeared after 5 years of colonization. This may be explained by the reduction in the substratum available for the first settlement (hydroid covering), as well as by the modification of the surface required for final settlement.

  5. Laser modification of graphene oxide layers

    NASA Astrophysics Data System (ADS)

    Malinský, Petr; Macková, Anna; Cutroneo, Mariapompea; Siegel, Jakub; Bohačová, Marie; Klímova, Kateřina; Švorčík, Václav; Sofer, Zdenĕk

    2018-01-01

    The effect of linearly polarized laser irradiation with various energy densities was successfully used for reduction of graphene oxide (GO). The ion beam analytical methods (RBS, ERDA) were used to follow the elemental composition which is expected as the consequence of GO reduction. The chemical composition analysis was accompanied by structural study showing changed functionalities in the irradiated GO foils using spectroscopy techniques including XPS, FTIR and Raman spectroscopy. The AFM was employed to identify the surface morphology and electric properties evolution were subsequently studied using standard two point method measurement. The used analytical methods report on reduction of irradiated graphene oxide on the surface and the decrease of surface resistivity as a growing function of the laser beam energy density.

  6. An Overview of the Chemistry and Biology of Reactive Aldehydes

    PubMed Central

    Fritz, Kristofer S.; Petersen, Dennis R.

    2012-01-01

    The non-enzymatic free radical generation of reactive aldehydes is known to contribute to diseases of sustained oxidative stress including rheumatoid arthritis, atherosclerosis, neurodegenerative and a number of liver diseases. At the same time, the accumulation of lipid electrophiles has been demonstrated to play a role in cell signaling events through modification of proteins critical for cellular homeostasis. Given the broad scope of reactivity profiles and the ability to modify numerous proteomic and genomic processes, new emphasis is being placed on a systems-based analysis of the consequences of electrophilic adduction. This review focuses on the generation and chemical reactivity of lipid-derived aldehydes with a special focus on the homeostatic responses to electrophilic stress. PMID:22750507

  7. A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis

    PubMed Central

    Down, Thomas A.; Rakyan, Vardhman K.; Turner, Daniel J.; Flicek, Paul; Li, Heng; Kulesha, Eugene; Gräf, Stefan; Johnson, Nathan; Herrero, Javier; Tomazou, Eleni M.; Thorne, Natalie P.; Bäckdahl, Liselotte; Herberth, Marlis; Howe, Kevin L.; Jackson, David K.; Miretti, Marcos M.; Marioni, John C.; Birney, Ewan; Hubbard, Tim J. P.; Durbin, Richard; Tavaré, Simon; Beck, Stephan

    2009-01-01

    DNA methylation is an indispensible epigenetic modification of mammalian genomes. Consequently there is great interest in strategies for genome-wide/whole-genome DNA methylation analysis, and immunoprecipitation-based methods have proven to be a powerful option. Such methods are rapidly shifting the bottleneck from data generation to data analysis, necessitating the development of better analytical tools. Until now, a major analytical difficulty associated with immunoprecipitation-based DNA methylation profiling has been the inability to estimate absolute methylation levels. Here we report the development of a novel cross-platform algorithm – Bayesian Tool for Methylation Analysis (Batman) – for analyzing Methylated DNA Immunoprecipitation (MeDIP) profiles generated using arrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). The latter is an approach we have developed to elucidate the first high-resolution whole-genome DNA methylation profile (DNA methylome) of any mammalian genome. MeDIP-seq/MeDIP-chip combined with Batman represent robust, quantitative, and cost-effective functional genomic strategies for elucidating the function of DNA methylation. PMID:18612301

  8. Sensitivity of Hawking radiation to superluminal dispersion relations

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

    Barcelo, C.; Garay, L. J.; Instituto de Estructura de la Materia, CSIC, Serrano 121, 28006 Madrid

    2009-01-15

    We analyze the Hawking radiation process due to collapsing configurations in the presence of superluminal modifications of the dispersion relation. With such superluminal dispersion relations, the horizon effectively becomes a frequency-dependent concept. In particular, at every moment of the collapse, there is a critical frequency above which no horizon is experienced. We show that, as a consequence, the late-time radiation suffers strong modifications, both quantitative and qualitative, compared to the standard Hawking picture. Concretely, we show that the radiation spectrum becomes dependent on the measuring time, on the surface gravities associated with different frequencies, and on the critical frequency. Evenmore » if the critical frequency is well above the Planck scale, important modifications still show up.« less

  9. Computational Micromodel for Epigenetic Mechanisms

    PubMed Central

    Raghavan, Karthika; Ruskin, Heather J.; Perrin, Dimitri; Goasmat, Francois; Burns, John

    2010-01-01

    Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach. PMID:21152421

  10. Estimating restorable wetland water storage at landscape scales

    EPA Science Inventory

    Globally, hydrologic modifications such as ditching and subsurface drainage have significantly reduced wetland water storage capacity (i.e., the volume of surface water a wetland can retain) and consequent wetland functions. While wetland area has been well documented across many...

  11. CARDIOVASCULAR CONSEQUENCES OF IMMUNE MODIFICATION BY TRAFFIC-RELATED EMISSIONS

    EPA Science Inventory

    Findings will 1) indicate the most potent combinations of urban roadway and background copollutants in terms of vascular toxicity and 2) detail the role of the immune system in mechanistically driving the systemic effects of inhaled pollutants.

  12. 10 CFR 963.17 - Postclosure suitability criteria.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Near field geochemical environment—for example, the chemical reactions and products resulting from... probability and potential consequences of a self-sustaining nuclear reaction as a result of chemical or..., drip shields, backfill, coatings, or chemical modifications, and (ii) Waste package degradation—for...

  13. 10 CFR 963.17 - Postclosure suitability criteria.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Near field geochemical environment—for example, the chemical reactions and products resulting from... probability and potential consequences of a self-sustaining nuclear reaction as a result of chemical or..., drip shields, backfill, coatings, or chemical modifications, and (ii) Waste package degradation—for...

  14. 10 CFR 963.17 - Postclosure suitability criteria.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Near field geochemical environment—for example, the chemical reactions and products resulting from... probability and potential consequences of a self-sustaining nuclear reaction as a result of chemical or..., drip shields, backfill, coatings, or chemical modifications, and (ii) Waste package degradation—for...

  15. 10 CFR 963.17 - Postclosure suitability criteria.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Near field geochemical environment—for example, the chemical reactions and products resulting from... probability and potential consequences of a self-sustaining nuclear reaction as a result of chemical or..., drip shields, backfill, coatings, or chemical modifications, and (ii) Waste package degradation—for...

  16. 10 CFR 963.17 - Postclosure suitability criteria.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Near field geochemical environment—for example, the chemical reactions and products resulting from... probability and potential consequences of a self-sustaining nuclear reaction as a result of chemical or..., drip shields, backfill, coatings, or chemical modifications, and (ii) Waste package degradation—for...

  17. Behavior Modification with an Aphasic Man

    ERIC Educational Resources Information Center

    Ince, Laurence P.

    1973-01-01

    Techniques based upon operant conditioning were employed with a male patient who had sustained a cerebrovascular accident with consequent right hemiplegia and expressive asphasia. A combination of positive verbal reinforcement and feedback of progress were utilized to improve language fluency and speed of typing. (Author)

  18. Surface-Modification of Carbonate Apatite Nanoparticles Enhances Delivery and Cytotoxicity of Gemcitabine and Anastrozole in Breast Cancer Cells

    PubMed Central

    Mozar, Fitya Syarifa; Chowdhury, Ezharul Hoque

    2017-01-01

    pH sensitive nanoparticles of carbonate apatite (CA) have been proven to be effective delivery vehicles for DNA, siRNAs and proteins. More recently, conventional anti-cancer drugs, such as doxorubicin, methotrexate and cyclophosphamide have been successfully incorporated into CA for intracellular delivery to breast cancer cells. However, physical and chemical properties of drug molecules appeared to affect their interactions with CA, with hydrophillic drug so far exhibiting better binding affinity and cellular uptakes compared to hydrophobic drugs. In this study, anastrozole, a non-steroidal aromatase inhibitor which is largely hydrophobic, and gemcitabine, a hydrophilic nucleoside inhibitor were used as solubility models of chemotherapy drug. Aggregation tendency of poorly soluble drugs resulting in larger particle-drug complex size might be the main factor hindering their delivery effectiveness. For the first time, surface modification of CA with poly(ethylene glycol) (PEG) has shown promising result to drastically reduce anastrozole- loaded CA particle size, from approximately 1000 to 500 nm based on zeta sizer analysis. Besides PEG, a cell specific ligand, in this case fibronectin, was attached to the particles in order to facilitate receptor mediated endocytosis based on fibronectin–integrin interaction. High-performance liquid chromatography (HPLC) was performed to measure uptake of the drugs by breast cancer cells, revealing that surface modification increased the drug uptake, especially for the hydrophobic drug, compared to the uncoated particles and the free drug. In vitro chemosensitivity assay and in vivo tumor regression study also showed that coated apatite/drug nanoparticle complexes presented higher cytotoxicity and tumor regression effects than uncoated apatite/drug nanoparticles and free drugs, indicating that surface modification successfully created optimum particles size with the consequence of more effective uptake along with favorable pharmacokinetics of the particles. PMID:28590445

  19. Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

    PubMed

    Calas, André-Guilhem; Richard, Olivier; Même, Sandra; Beloeil, Jean-Claude; Doan, Bich-Thuy; Gefflaut, Thierry; Même, William; Crusio, Wim E; Pichon, Jacques; Montécot, Céline

    2008-07-01

    Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

  20. Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents.

    PubMed

    McCormack, S E; McCarthy, M A; Harrington, S G; Farilla, L; Hrovat, M I; Systrom, D M; Thomas, B J; Torriani, M; McInnis, K; Grinspoon, S K; Fleischman, A

    2014-08-01

    Obesity is associated with poor fitness and adverse metabolic consequences in children. To investigate how exercise and lifestyle modification may improve fitness and insulin sensitivity in this population. Randomized controlled trial, 21 obese (body mass index ≥ 95% percentile) subjects, ages 10 to 17 years. Subjects were given standardized healthful lifestyle advice for 8 weeks. In addition, they were randomized to an in-home supervised exercise intervention (n = 10) or control group (n = 11). Fasting laboratory studies (insulin, glucose, lipid profile) and assessments of fitness, body composition, skeletal muscle oxidative phosphorylation and intramyocellular lipid content (IMCL), were performed at baseline and study completion. Subjects were 13.0 ± 1.9 (standard deviation) years old, 72% female and 44% non-white. Exercise improved fitness (P = 0.03) and power (P = 0.01), and increased IMCL (P = 0.02). HOMA-IR decreased among all subjects in response to lifestyle modification advice (P = 0.01), regardless of exercise training assignment. In univariate analysis in all subjects, change in cardiovascular fitness was associated with change in HOMA-IR. In exploratory analyses, increased IMCL was associated with greater resting energy expenditure (r = 0.78, P = 0.005) and a decrease in fasting respiratory quotient (r = -0.70, P = 0.02) (n = 11). Change in fitness was found to be related to change in insulin resistance in response to lifestyle modification and exercise in obese children. IMCL increased with exercise in these obese children, which may reflect greater muscle lipid oxidative capacity. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

  1. MSR performance enhancements and modifications at St. Lucie Power Plant

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

    Rubano, V.F.; Ugelow, A.G.; Menocal, A.G.

    1989-01-01

    The St. Lucie Power Plant provides an excellent historical prospective on various moisture separator/reheater improvements. Between the two essentially identical units there is a total of 14 years of operating experience with various moisture separator/reheater configurations, with a combination of four different heat transfer surfaces and three moisture removal configurations. Through various modifications and enhancements, the performance and the reliability of the moisture separator/reheaters at the St. Lucie Power Plant and consequently the overall plant performance has been improved. This improvement has taken place over several years and involves changes in both the heat transfer and moisture removal areas. Thismore » paper provides an overview of the history and description of moisture separator/reheater modifications at the St. Lucie Power Plant with the resulting performance improvements.« less

  2. ATLAS particle detector CSC ROD software design and implementation, and, Addition of K physics to chi-squared analysis of FDQM

    NASA Astrophysics Data System (ADS)

    Hawkins, Donovan Lee

    In this thesis I present a software framework for use on the ATLAS muon CSC readout driver. This C++ framework uses plug-in Decoders incorporating hand-optimized assembly language routines to perform sparsification and data formatting. The software is designed with both flexibility and performance in mind, and runs on a custom 9U VME board using Texas Instruments TMS360C6203 digital signal processors. I describe the requirements of the software, the methods used in its design, and the results of testing the software with simulated data. I also present modifications to a chi-squared analysis of the Standard Model and Four Down Quark Model (FDQM) originally done by Dr. Dennis Silverman. The addition of four new experiments to the analysis has little effect on the Standard Model but provides important new restrictions on the FDQM. The method used to incorporate these new experiments is presented, and the consequences of their addition are reviewed.

  3. Siblings of the Handicapped: Maladjustment and Its Prevention.

    ERIC Educational Resources Information Center

    Hannah, Mary Elizabeth; Midlarsky, Elizabeth

    1987-01-01

    The mental health consequences of having a handicapped brother or sister and factors that may be related to psychological adjustment are discussed. Also explored are the use of parental consultation, behavior modification, and discussion groups as potential intervention strategies with siblings of the handicapped. (Author)

  4. Final (Tier 1) environmental impact statement for the Galileo and Ulysses Missions

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Presented here is a Final (Tier 1) Environmental Impact Statement (EIS) addressing the potential environmental consequences associated with continuing the modifications of the Galileo and Ulysses spacecraft for launch using a booster/upper stage combination that is different from the one planned for use prior to the Challenger accident, while conducting the detailed safety and environmental analysis in order to preserve the October 1989 launch opportunity for Galileo and an October 1990 launch opportunity for Ulysses. While detailed safety and environmental analyses associated with the missions are underway, they currently are not complete. Nevertheless, sufficient information is available to enable a choice among the reconfiguration alternatives presented. Relevant assessments of the potential for environmental impacts are presented.

  5. Fast changes in seasonal forest communities due to soil moisture increase after damming.

    PubMed

    do Vale, Vagner Santiago; Schiavini, Ivan; Araújo, Glein Monteiro; Gusson, André Eduardo; Lopes, Sérgio de Faria; de Oliveira, Ana Paula; do Prado-Júnior, Jamir Afonso; Arantes, Carolina de Silvério; Dias-Neto, Olavo Custodio

    2013-12-01

    Local changes caused by dams can have drastic consequences for ecosystems, not only because they change the water regime but also the modification on lakeshore areas. Thus, this work aimed to determine the changes in soil moisture after damming, to understand the consequences of this modification on the arboreal community of dry forests, some of the most endangered systems on the planet. We studied these changes in soil moisture and the arboreal community in three dry forests in the Araguari River Basin, after two dams construction in 2005 and 2006, and the potential effects on these forests. For this, plots of 20 m x 10 m were distributed close to the impoundment margin and perpendicular to the dam margin in two deciduous dry forests and one semi-deciduous dry forest located in Southeastern Brazil, totaling 3.6 ha sampled. Besides, soil analysis were undertaken before and after impoundment at three different depths (0-10, 20-30 and 40-50 cm). A tree (minimum DBH of 4.77 cm) community inventory was made before (TO) and at two (T2) and four (T4) years after damming. Annual dynamic rates of all communities were calculated, and statistical tests were used to determine changes in soil moisture and tree communities. The analyses confirmed soil moisture increases in all forests, especially during the dry season and at sites closer to the reservoir; besides, an increase in basal area due to the fast growth of many trees was observed. The highest turnover occurred in the first two years after impoundment, mainly due to the higher tree mortality especially of those closer to the dam margin. All forests showed reductions in dynamic rates for subsequent years (T2-T4), indicating that these forests tended to stabilize after a strong initial impact. The modifications were more extensive in the deciduous forests, probably because the dry period resulted more rigorous in these forests when compared to semideciduous forest. The new shorelines created by damming increased soil moisture in the dry season, making plant growth easier. We concluded that several changes occurred in the T0-T2 period and at 0-30 m to the impoundment, mainly for the deciduous forests, where this community turned into a "riparian-deciduous forest" with large basal area in these patches. However, unlike other transitory disturbances, damming is a permanent alteration and transforms the landscape to a different scenario, probably with major long-term consequences for the environment.

  6. Postural habits of young adults and possibilities of modification.

    PubMed

    Nowotny-Czupryna, Olga; Czupryna, Krzysztof; Bąk, Krzysztof; Wróblewska, Ewa; Rottermund, Jerzy

    2013-01-01

    The aim of the study was to assess postural habits in young, healthy people, identify correlations between postural errors and pain and attempt to modify bad habits. 144 people, aged 18-23 were enrolled. The intervention consisted of 4 stages: Stage 1 - identification of postural habits, description of responses to stress, back pain frequency and intensity (Jackson & Moskowitz); Stage 2 - correction of habitual position with the help of a physiotherapist, briefing about ergonomic everyday behaviours and consequences of continued non-ergonomic behaviours, Stage 3 - follow-up examination: self-assessment of changes, evaluation of the effects of modifications, determination of causes for discontinuing the behaviour modification programme, where applicable; and Stage 4 - final examination, assessment of results. Correlations were sought between inappropriate postural behaviour in various positions and between non-ergonomic postural behaviour and pain location and response to stress. Statistical analysis was carried out with Excel and Statistica v. 7.1. A non-parametric χ(2) test was used at p<0.005. All participants presented poor postural patterns in the standing, sitting and recumbent position. Back pain was reported by half of the participants. Statistically significant relationships between pain and habitual positions were noted with regard to the cervical and lumbar spine and also for abdominal pain as a response to stress in people with excessive thoracic kyphosis. Behaviour modifications caused or intensified lumbar pain or thigh muscle pain. Positive outcomes included better urination and/or defecation and greater comfort in assuming the different positions and performing activities of daily living in these positions. Some examinees discontinued behaviour modification during the first month after the initial instruction and the majority did so over the next three months. 1. Non-ergonomic postural behaviours are common among young people. 2. Changing the body position does not eliminate the impact of the inappropriate habit. 3. An attempt to modify non-ergonomic postural behaviours usually results in pain, which may act as a demotivating factor. 4. Discomfort associated with the modification of habitual postural behaviours is reduced after 3-4 months of regular training.

  7. Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health.

    PubMed

    Herndon, J Marvin

    2015-08-11

    The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un-leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction.

  8. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

    PubMed Central

    Groebner, Jennifer L.; Tuma, Pamela L.

    2015-01-01

    The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease. PMID:26393662

  9. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.

    PubMed

    Groebner, Jennifer L; Tuma, Pamela L

    2015-09-18

    The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the "tubulin code" are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

  10. Note: Work function change measurement via improved Anderson method

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

    Sabik, A., E-mail: sabik@ifd.uni.wroc.pl; Gołek, F.; Antczak, G.

    We propose the modification to the Anderson method of work function change (Δϕ) measurements. In this technique, the kinetic energy of the probing electrons is already low enough for non-destructive investigation of delicate molecular systems. However, in our implementation, all electrodes including filament of the electron gun are polarized positively. As a consequence, electron bombardment of any elements of experimental system is eliminated. Our modification improves cleanliness of the ultra-high vacuum system. As an illustration of the solution capabilities, we present Δϕ of the Ag(100) surface induced by cobalt phthalocyanine layers.

  11. Study of recent changes of weathering dynamic in soils based on Sr and U isotope ratios in soil solutions (Strengbach catchment- Vosges, France)

    NASA Astrophysics Data System (ADS)

    Prunier, Jonathan; Chabaux, François; Stille, Peter; Pierret, Marie-Claire; Viville, Daniel; Gangloff, Sophie

    2015-04-01

    Major and trace element concentrations along with U and Sr isotopic ratios of the main components of the water-soil-plant system of two experimental plots in a forested silicate catchment were determined to characterize the day-present weathering processes within the surface soil levels and to identify the nature of minerals which control the lithogenic flux of the soil solutions. This study allows recognition of a lithogenic origin of the dissolved U in the surface soil solutions, even in the most superficial ones, implying that the colloidal U is a U secondarily associated with organic matter or organo-metallic complexes. This flux significantly varies in the upper meter of the soil and between the two sites, due to their slightly different bedrock lithologies and likely also to their different vegetation covers. A long-time monitoring during the past 15 years was achieved to evaluate the response of this ecosystem to recent environmental changes. A clear decrease of the Ca and K fluxes exported by the soil solutions between 1992 and 2006 at the spruce site was observed, while this decrease is much smaller for the beech plot. In addition, the Sr isotope ratios of soil solutions vary significantly between 1998 and 2004, with once again a much more important change for the spruce site than for the beech site. It demonstrates that the source of elements in soil solutions has changed over this time period due to a modification of the weathering reactions occurring within the weathering profile. The origin of the weathering modification could be the consequence of the acid rains on weathering granitic bedrock or a consequence of forest exploitation incompatible with the nutriment reserve of soils with recent plantations of conifer, which impoverish soils. All together, these data suggest that the forest ecosystem at the spruce plot is in a transient state of functioning marked by a possible recent modification of weathering reactions. This study shows the potential of the approach combining the analysis of U and Sr isotopes in soil solutions and vegetation to evaluate this kind of phenomenon.

  12. 78 FR 26716 - Airworthiness Directives; Airbus Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... currently requires a repetitive inspection program on certain check valves in the hydraulic systems that... hydraulic systems on airplanes that have had a certain modification embodied during production or in-service... hydraulic leaks, possibly leading to the loss of all three hydraulic systems and consequent loss of control...

  13. College Psychiatry 2006: Challenges and Opportunities

    ERIC Educational Resources Information Center

    Kadison, Richard

    2006-01-01

    This article discusses some of the dramatic changes seen in college mental health issues over the past 2 decades. These modifications are a consequence of many factors: changes in our health care system (managed care), new effective biological treatments (medications), the focus of psychiatric training (biologic focus), technology advances…

  14. Gene flow in genetically engineered perennial grasses: Lessons for modification of dedicated bioenergy crops

    EPA Science Inventory

    The potential ecological consequences of the commercialization of genetically engineered (GD) crops have been the subject of intense debate, particularly when the GE crops are perennial and capable of outcrossing to wild relatives. The essential ecological impact issues for engi...

  15. Sleep modifications in acute transient global amnesia.

    PubMed

    Della Marca, Giacomo; Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Broccolini, Aldobrando; Frisullo, Giovanni; Marano, Giuseppe; Morosetti, Roberta; Pilato, Fabio; Profice, Paolo; Vollono, Catello; Di Lazzaro, Vincenzo

    2013-09-15

    Transient global amnesia (TGA) is a temporary memory loss characterized by an abrupt onset of antero-grade and retrograde amnesia, totally reversible. Since sleep plays a major role in memory consolidation, and in the storage of memory-related traces into the brain cortex, the aims of the present study were: (1) to evaluate changes in sleep macro-structure in TGA; (2) to assess modifications in sleep micro-structure in TGA, with particular reference to the arousal EEG and to cyclic alternating pattern (CAP); (3) to compare sleep parameters in TGA patients with a control group of patients with acute ischemic events ("minor stroke" or transient ischemic attack [TIA]) clinically and neuroradiologically "similar" to the TGA. TGA GROUP: 17 patients, (8 men and 9 women, 60.2 ± 12.5 years). Stroke or TIA (SoT) group: 17 patients hospitalized in the Stroke Unit for recent onset of minor stroke or TIA with hemispheric localization; healthy controls (HC) group: 17 healthy volunteers, matched for age and sex. Patients and controls underwent full-night polysomnography. In the multivariate analysis (conditions TGA, SoT, and HC) a significant effect of the condition was observed for sleep efficiency index, number of awakenings longer 1 min, REM latency, CAP time, and CAP rate. TGA and SoT differed only for CAP time and CAP rate, which were lower in the TGA group. Microstructural modification associated with tga could be consequent to: (1) hippocampal dysfunction and memory impairment; (2) impairment of arousal-related structures (in particular, cholinergic pathways); (3) emotional distress.

  16. Lead tolerance of water hyacinth (Eichhornia crassipes Mart. - Pontederiaceae) as defined by anatomical and physiological traits.

    PubMed

    Pereira, Fabricio J; Castro, Evaristo M de; Oliveira, Cynthia de; Pires, Marinês F; Pereira, Marcio P; Ramos, Silvio J; Faquin, Valdemar

    2014-09-01

    This study aimed at verifying the lead tolerance of water hyacinth and at looking at consequent anatomical and physiological modifications. Water hyacinth plants were grown on nutrient solutions with five different lead concentrations: 0.00, 0.50, 1.00, 2.00 and 4.00 mg L-1 by 20 days. Photosynthesis, transpiration, stomatal conductance and the Ci/Ca rate were measured at the end of 15 days of experiment. At the end of the experiment, the anatomical modifications in the roots and leaves, and the activity of antioxidant system enzymes, were evaluated. Photosynthetic and Ci/Ca rates were both increased under all lead treatments. Leaf anatomy did not exhibit any evidence of toxicity effects, but showed modifications of the stomata and in the thickness of the palisade and spongy parenchyma in the presence of lead. Likewise, root anatomy did not exhibit any toxicity effects, but the xylem and phloem exhibited favorable modifications as well as increased apoplastic barriers. All antioxidant system enzymes exhibited increased activity in the leaves, and some modifications in roots, in the presence of lead. It is likely, therefore, that water hyacinth tolerance to lead is related to anatomical and physiological modifications such as increased photosynthesis and enhanced anatomical capacity for CO2 assimilation and water conductance.

  17. A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

    PubMed Central

    Zaborske, John M.; Bauer DuMont, Vanessa L.; Wallace, Edward W. J.; Pan, Tao; Aquadro, Charles F.; Drummond, D. Allan

    2014-01-01

    Natural selection favors efficient expression of encoded proteins, but the causes, mechanisms, and fitness consequences of evolved coding changes remain an area of aggressive inquiry. We report a large-scale reversal in the relative translational accuracy of codons across 12 fly species in the Drosophila/Sophophora genus. Because the reversal involves pairs of codons that are read by the same genomically encoded tRNAs, we hypothesize, and show by direct measurement, that a tRNA anticodon modification from guanosine to queuosine has coevolved with these genomic changes. Queuosine modification is present in most organisms but its function remains unclear. Modification levels vary across developmental stages in D. melanogaster, and, consistent with a causal effect, genes maximally expressed at each stage display selection for codons that are most accurate given stage-specific queuosine modification levels. In a kinetic model, the known increased affinity of queuosine-modified tRNA for ribosomes increases the accuracy of cognate codons while reducing the accuracy of near-cognate codons. Levels of queuosine modification in D. melanogaster reflect bioavailability of the precursor queuine, which eukaryotes scavenge from the tRNAs of bacteria and absorb in the gut. These results reveal a strikingly direct mechanism by which recoding of entire genomes results from changes in utilization of a nutrient. PMID:25489848

  18. Passive control of the flow around unsteady aerofoils using a self-activated deployable flap

    NASA Astrophysics Data System (ADS)

    Rosti, Marco E.; Omidyeganeh, Mohammad; Pinelli, Alfredo

    2018-03-01

    Self-activated feathers are used by many birds to adapt their wing characteristics to the sudden change of flight incidence angle. In particular, dorsal feathers are believed to pop-up as a consequence of unsteady flow separation and to interact with the flow to palliate the sudden stall breakdown typical of dynamic stall. Inspired by the adaptive character of birds feathers, some authors have envisaged the potential benefits of using of flexible flaps mounted on aerodynamic surfaces to counteract the negative aerodynamic effects associated with dynamic stall. This contribution explores more in depth the physical mechanisms that play a role in the modification of the unsteady flow field generated by a NACA0020 aerofoil equipped with an elastically mounted flap undergoing a specific ramp-up manoeuvre. We discuss the design of flaps that limit the severity of the dynamic stall breakdown by increasing the value of the lift overshoot also smoothing its abrupt decay in time. A detailed analysis on the modification of the turbulent and unsteady vorticity field due to the flap flow interaction during the ramp-up motion is also provided to explain the more benign aerodynamic response obtained when the flap is in use.

  19. Effective theory of dark energy at redshift survey scales

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

    Gleyzes, Jérôme; Mancarella, Michele; Vernizzi, Filippo

    2016-02-01

    We explore the phenomenological consequences of general late-time modifications of gravity in the quasi-static approximation, in the case where cold dark matter is non-minimally coupled to the gravitational sector. Assuming spectroscopic and photometric surveys with configuration parameters similar to those of the Euclid mission, we derive constraints on our effective description from three observables: the galaxy power spectrum in redshift space, tomographic weak-lensing shear power spectrum and the correlation spectrum between the integrated Sachs-Wolfe effect and the galaxy distribution. In particular, with ΛCDM as fiducial model and a specific choice for the time dependence of our effective functions, we performmore » a Fisher matrix analysis and find that the unmarginalized 68% CL errors on the parameters describing the modifications of gravity are of order σ∼10{sup −2}–10{sup −3}. We also consider two other fiducial models. A nonminimal coupling of CDM enhances the effects of modified gravity and reduces the above statistical errors accordingly. In all cases, we find that the parameters are highly degenerate, which prevents the inversion of the Fisher matrices. Some of these degeneracies can be broken by combining all three observational probes.« less

  20. Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli

    PubMed Central

    Boamah, Ernest K.; Kotova, Elena; Garabedian, Mikael; Jarnik, Michael; Tulin, Alexei V.

    2012-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis. PMID:22242017

  1. Data-driven human rights: using the electronic health record to promote human rights in jail.

    PubMed

    Glowa-Kollisch, Sarah; Andrade, Kelly; Stazesky, Richard; Teixeira, Paul; Kaba, Fatos; Macdonald, Ross; Rosner, Zachary; Selling, Daniel; Parsons, Amanda; Venters, Homer

    2014-06-14

    The electronic health record (EHR) is a commonplace innovation designed to promote efficiency, quality, and continuity of health services. In the New York City jail system, we implemented an EHR across 12 jails between 2008 and 2011. During the same time, our work increasingly focused on the importance of human rights as an essential element to the provision of medical and mental health care for our patients. Consequently, we made major modifications to the EHR to allow for better surveillance of vulnerable populations and enable reporting and analysis of patterns of abuse, neglect, and other patient concerns related to human rights. These modifications have improved our ability to find and care for patients injured in jail and those with mental health exacerbations. More work is needed, however, to optimize the potential of the EHR as a tool to promote human rights among patients in jail. Copyright © 2014 Sheffield, Durante, Rahona, and Zarcadoolas. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  2. Epigenetic chromatin silencing: bistability and front propagation

    NASA Astrophysics Data System (ADS)

    Sedighi, Mohammad; Sengupta, Anirvan M.

    2007-12-01

    The role of post-translational modification of histones in eukaryotic gene regulation is well recognized. Epigenetic silencing of genes via heritable chromatin modifications plays a major role in cell fate specification in higher organisms. We formulate a coarse-grained model of chromatin silencing in yeast and study the conditions under which the system becomes bistable, allowing for different epigenetic states. We also study the dynamics of the boundary between the two locally stable states of chromatin: silenced and unsilenced. The model could be of use in guiding the discussion on chromatin silencing in general. In the context of silencing in budding yeast, it helps us understand the phenotype of various mutants, some of which may be non-trivial to see without the help of a mathematical model. One such example is a mutation that reduces the rate of background acetylation of particular histone side chains that competes with the deacetylation by Sir2p. The resulting negative feedback due to a Sir protein depletion effect gives rise to interesting counter-intuitive consequences. Our mathematical analysis brings forth the different dynamical behaviors possible within the same molecular model and guides the formulation of more refined hypotheses that could be addressed experimentally.

  3. Microscopic mechanism of amino silicone oil modification and modification effect with different amino group contents based on molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    He, Liping; Li, Wenjun; Chen, Dachuan; Yuan, Jianmin; Lu, Gang; Zhou, Dianwu

    2018-05-01

    The microscopic mechanism of amino silicone oil (ASO) modification of natural fiber was investigated for the first time using molecular dynamics (MD) simulation at the atomic and molecular levels. The MD simulation results indicated that the ASO molecular interacted with the cellulose molecular within the natural fiber, mainly by intermolecular forces of Nsbnd Hsbnd O and Osbnd Hsbnd N hydrogen bonds and the molecular chain of ASO absorbed onto the natural fiber in a selective orientation, i.e., the hydrophobic alkyl groups (sbnd CnH2n+1) project outward and the polar amino groups (sbnd NH2) point to the surface of natural fiber. Consequently, the ASO modification changed the surface characteristic of natural fiber from hydrophilic to hydrophobic. Furthermore, the modification effects of the ASO modification layer with different amino group contents (m:n ratio) were also evaluated in this study by calculating the binding energy between the ASO modifier and natural fiber, and the cohesive energy density and free volume of the ASO modification layer. The results showed that the binding energy reached a maximum when the m:n ratio of ASO was of 8:4, suggesting that a good bonding strength was achieved at this m:n ratio. It was also found that the cohesive energy density enhanced with the increase in the amino group content, and the higher the cohesive energy density, the easier the formation of the ASO modification layer. However, the fraction free volume decreased with the increase in the amino group content. This is good for improving the water-proof property of natural fiber. The present work can provide an effective method for predicting the modification effects and designing the optimized m:n ratio of ASO modification.

  4. Comprehensive Analysis of Protein Modifications by Top-down Mass Spectrometry

    PubMed Central

    Zhang, Han; Ge, Ying

    2012-01-01

    Mass spectrometry (MS)-based proteomics is playing an increasingly important role in cardiovascular research. Proteomics includes not only identification and quantification of proteins, but also the characterization of protein modifications such as post-translational modifications and sequence variants. The conventional bottom-up approach, involving proteolytic digestion of proteins into small peptides prior to MS analysis, is routinely used for protein identification and quantification with high throughput and automation. Nevertheless, it has limitations in the analysis of protein modifications mainly due to the partial sequence coverage and loss of connections among modifications on disparate portions of a protein. An alternative approach, top-down MS, has emerged as a powerful tool for the analysis of protein modifications. The top-down approach analyzes whole proteins directly, providing a “bird’s eye” view of all existing modifications. Subsequently, each modified protein form can be isolated and fragmented in the mass spectrometer to locate the modification site. The incorporation of the non-ergodic dissociation methods such as electron capture dissociation (ECD) greatly enhances the top-down capabilities. ECD is especially useful for mapping labile post-translational modifications which are well-preserved during the ECD fragmentation process. Top-down MS with ECD has been successfully applied to cardiovascular research with the unique advantages in unraveling the molecular complexity, quantifying modified protein forms, complete mapping of modifications with full sequence coverage, discovering unexpected modifications, and identifying and quantifying positional isomers and determining the order of multiple modifications. Nevertheless, top-down MS still needs to overcome some technical challenges to realize its full potential. Herein, we reviewed the advantages and challenges of top-down methodology with a focus on its application in cardiovascular research. PMID:22187450

  5. Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts

    PubMed Central

    Eggink, Laura L.; Chen, Min

    2007-01-01

    Chlorophyll (Chl) b serves an essential function in accumulation of light-harvesting complexes (LHCs) in plants. In this article, this role of Chl b is explored by considering the properties of Chls and the ligands with which they interact in the complexes. The overall properties of the Chls, not only their spectral features, are altered as consequences of chemical modifications on the periphery of the molecules. Important modifications are introduction of oxygen atoms at specific locations and reduction or desaturation of sidechains. These modifications influence formation of coordination bonds by which the central Mg atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts principally with imidazole groups but also with sidechain amides and water. The 7-formyl group on Chl b withdraws electron density toward the periphery of the molecule and consequently the positive Mg is less shielded by the molecular electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with Lewis bases with a fixed dipole, such as water and, in particular, peptide backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between the protein and the 7-formyl group. These additional strong interactions with Chl b are necessary to achieve assembly of stable LHCs. PMID:17505910

  6. Influence of modified muscle morphology and activity pattern on the results of musculoskeletal system modelling in cerebral palsy patient.

    PubMed

    Ogrodnik, Justyna; Piszczatowski, Szczepan

    2017-01-01

    The aim of the present study was to evaluate the influence of modified morphological parameters of the muscle model and excitation pattern on the results of musculoskeletal system numerical simulation in a cerebral palsy patient. The modelling of the musculoskeletal system was performed in the AnyBody Modelling System. The standard model (MoCap) was subjected to modifications consisting of changes in morphological parameters and excitation patterns of selected muscles. The research was conducted with the use of data of a 14-year-old cerebral palsy patient. A reduction of morphological parameters (variant MI) caused a decrease in the value of active force generated by the muscle with changed geometry, and as a consequence the changes in active force generated by other muscles. A simulation of the abnormal excitation pattern (variant MII) resulted in the muscle's additional activity during its lengthening. The simultaneous modification of the muscle morphology and excitation pattern (variant MIII) points to the interdependence of both types of muscle model changes. A significant increase in the value of the reaction force in the hip joint was observed as a consequence of modification of the hip abductor activity. The morphological parameters and the excitation pattern of modelled muscles have a significant influence on the results of numerical simulation of the musculoskeletal system functioning.

  7. Using Incentives To Promote Employee Health. WBGH Worksite Wellness Series.

    ERIC Educational Resources Information Center

    Yenney, Sharon L.

    The use of incentives by businesses is a well-accepted pattern of management-employee collaboration. Increasingly, U.S. businesses are using incentives to encourage employees to stay healthy. Research in the field of behavior modification indicates that positive reinforcement, negative consequences and restrictions, and feedback have great…

  8. Differences in Student Outcomes between Block, Semester, and Trimester Schedules.

    ERIC Educational Resources Information Center

    McCreary, Jason; Hausman, Charles

    Despite the popularity of schedule modifications as a cost-effective reform to improve student outcomes, little empirical research on the consequences of alternative schedules has been conducted. The literature has been dominated by anecdotal reports. Even when empirical evidence is examined, causal comparisons of school outcomes between schedules…

  9. Behavior Modification: Basic Principles. Third Edition

    ERIC Educational Resources Information Center

    Lee, David L.; Axelrod, Saul

    2005-01-01

    This classic book presents the basic principles of behavior emphasizing the use of preventive techniques as well as consequences naturally available in the home, business, or school environment to change important behaviors. This book, and its companion piece, "Measurement of Behavior," represents more than 30 years of research and strategies in…

  10. Changing feedbacks in the climate-biosphere system

    Treesearch

    F. Stuart Chapin; James T. Randerson; A. David McGuire; Jonathan A. Foley; Christopher B. Field

    2008-01-01

    Ecosystems influence climate through multiple pathways, primarily by changing the energy, water, and greenhouse-gas balance of the atmosphere. Consequently, efforts to mitigate climate change through modification of one pathway, as with carbon in the Kyoto Protocol, only partially address the issue of ecosystem-climate interactions. For example, the cooling of climate...

  11. The impact of considering land intensification and updated data on biofuels land use change and emissions estimates.

    DOT National Transportation Integrated Search

    2017-01-01

    Background: The GTAP model has been used to estimate biofuel policy induced land use changes and consequent GHG emissions for more than a decade. This paper reviews the history of the model and database modifications and improvements that have occurr...

  12. [Formula: see text] regularity properties of singular parameterizations in isogeometric analysis.

    PubMed

    Takacs, T; Jüttler, B

    2012-11-01

    Isogeometric analysis (IGA) is a numerical simulation method which is directly based on the NURBS-based representation of CAD models. It exploits the tensor-product structure of 2- or 3-dimensional NURBS objects to parameterize the physical domain. Hence the physical domain is parameterized with respect to a rectangle or to a cube. Consequently, singularly parameterized NURBS surfaces and NURBS volumes are needed in order to represent non-quadrangular or non-hexahedral domains without splitting, thereby producing a very compact and convenient representation. The Galerkin projection introduces finite-dimensional spaces of test functions in the weak formulation of partial differential equations. In particular, the test functions used in isogeometric analysis are obtained by composing the inverse of the domain parameterization with the NURBS basis functions. In the case of singular parameterizations, however, some of the resulting test functions do not necessarily fulfill the required regularity properties. Consequently, numerical methods for the solution of partial differential equations cannot be applied properly. We discuss the regularity properties of the test functions. For one- and two-dimensional domains we consider several important classes of singularities of NURBS parameterizations. For specific cases we derive additional conditions which guarantee the regularity of the test functions. In addition we present a modification scheme for the discretized function space in case of insufficient regularity. It is also shown how these results can be applied for computational domains in higher dimensions that can be parameterized via sweeping.

  13. Heroin shortage in Coastal Kenya: A rapid assessment and qualitative analysis of heroin users’ experiences

    PubMed Central

    Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard

    2016-01-01

    Introduction While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors. Methods As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage. Results Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence. Conclusions The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact. PMID:26470646

  14. Heroin shortage in Coastal Kenya: A rapid assessment and qualitative analysis of heroin users' experiences.

    PubMed

    Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard

    2016-04-01

    While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors. As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage. Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence. The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact. Published by Elsevier B.V.

  15. Readiness of adolescents to use genetically modified organisms according to their knowledge and emotional attitude towards GMOs.

    PubMed

    Lachowski, Stanisław; Jurkiewicz, Anna; Choina, Piotr; Florek-Łuszczki, Magdalena; Buczaj, Agnieszka; Goździewska, Małgorzata

    2017-06-07

    Agriculture based on genetically modified organisms plays an increasingly important role in feeding the world population, which is evidenced by a considerable growth in the size of land under genetically modified crops (GM). Uncertainty and controversy around GM products are mainly due to the lack of accurate and reliable information, and lack of knowledge concerning the essence of genetic modifications, and the effect of GM food on the human organism, and consequently, a negative emotional attitude towards what is unknown. The objective of the presented study was to discover to what extent knowledge and the emotional attitude of adolescents towards genetically modified organisms is related with acceptance of growing genetically modified plants or breeding GM animals on own farm or allotment garden, and the purchase and consumption of GM food, as well as the use of GMOs in medicine. The study was conducted by the method of a diagnostic survey using a questionnaire designed by the author, which covered a group of 500 adolescents completing secondary school on the level of maturity examination. The collected material was subjected to statistical analysis. Research hypotheses were verified using chi-square test (χ 2 ), t-Student test, and stepwise regression analysis. Stepwise regression analysis showed that the readiness of adolescents to use genetically modified organisms as food or for the production of pharmaceuticals, the production of GM plants or animals on own farm, depends on an emotional-evaluative attitude towards GMOs, and the level of knowledge concerning the essence of genetic modifications.

  16. Protein mass analysis of histones.

    PubMed

    Galasinski, Scott C; Resing, Katheryn A; Ahn, Natalie G

    2003-09-01

    Posttranslational modification of chromatin-associated proteins, including histones and high-mobility-group (HMG) proteins, provides an important mechanism to control gene expression, genome integrity, and epigenetic inheritance. Protein mass analysis provides a rapid and unbiased approach to monitor multiple chemical modifications on individual molecules. This review describes methods for acid extraction of histones and HMG proteins, followed by separation by reverse-phase chromatography coupled to electrospray ionization mass spectrometry (LC/ESI-MS). Posttranslational modifications are detected by analysis of full-length protein masses. Confirmation of protein identity and modification state is obtained through enzymatic digestion and peptide sequencing by MS/MS. For differentially modified forms of each protein, the measured intensities are semiquantitative and allow determination of relative abundance and stoichiometry. The method simultaneously detects covalent modifications on multiple proteins and provides a facile assay for comparing chromatin modification states between different cell types and/or cellular responses.

  17. Pristine and γ-irradiated halloysite reinforced epoxy nanocomposites - Insight study

    NASA Astrophysics Data System (ADS)

    Saif, Muhammad Jawwad; Naveed, Muhammad; Zia, Khalid Mahmood; Asif, Muhammad

    2016-10-01

    The present study focuses on development of epoxy system reinforced with naturally occurring halloysite nanotubes (HNTs). A comparative study is presented describing the performance of pristine and γ-irradiated HNTs in an epoxy matrix. The γ-irradiation treatment was used for structural modification of natural pristine HNTs under air sealed environment at different absorbed doses and subsequently these irradiated HNTs were incorporated in epoxy resin with various wt% loadings. The consequences of γ-irradiation on HNTs were studied by FTIR and X-ray diffraction analysis (XRD) in terms of changes in functional groups and crystalline characteristics. An improvement is observed in mechanical properties and crack resistance of composites reinforced with γ-irradiated HNTs. The irradiated HNTs imparted an improved flexural and tensile strength/modulus along with better thermal performance.

  18. Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

    PubMed Central

    Kuan, Seah Ling; Wang, Tao

    2016-01-01

    Abstract The synthetic transformation of polypeptides with molecular accuracy holds great promise for providing functional and structural diversity beyond the proteome. Consequently, the last decade has seen an exponential growth of site‐directed chemistry to install additional features into peptides and proteins even inside living cells. The disulfide rebridging strategy has emerged as a powerful tool for site‐selective modifications since most proteins contain disulfide bonds. In this Review, we present the chemical design, advantages and limitations of the disulfide rebridging reagents, while summarizing their relevance for synthetic customization of functional protein bioconjugates, as well as the resultant impact and advancement for biomedical applications. PMID:27778400

  19. Excessive responsibility in obsessional concerns: a fine-grained experimental analysis.

    PubMed

    Ladouceur, R; Rhéaume, J; Aublet, F

    1997-05-01

    Excessive responsibility has been suggested as a central cognitive variable associated with Obsessive-Compulsive Disorder (OCD) (Rachman, 1993, Behaviour Research and Therapy, 31, 149-154; Salkovskis, 1985, Behaviour Research and Therapy, 23, 571-583; Salkovskis, 1989, Behaviour Research and Therapy, 27, 677-682; Salkovskis, 1995, Current controversies in the anxiety disorders). Several studies using questionnaires (e.g. Rhéaume, Freeston, Dugas, Letarte & Ladouceur, 1995, Behaviour Research and Therapy, 33, 785-794) and experimental manipulations (Ladouceur et al., 1995, Behaviour Research and Therapy, 33, 937-946; Lopatka & Rachman, 1995, Behaviour Research and Therapy, 33, 673-684) have shown evidence for such a link between responsibility and obsessive-compulsive symptoms. Responsibility has been defined as the belief of possessing a pivotal power to provoke or preventing crucial negative consequences (Salkovskis et al., 1992 cited in Salkovskis, 1995, Current controversies in the anxiety disorders). This definition emphasizes two related cognitive distortions: personal influence and potential negative consequences. The respective roles of each component and their potential interaction need to be clarified. The present study tests the effects of an experimental manipulation of both influence and negative consequences on perceived responsibility and checking behavior during a classification task. Seventy-seven subjects were divided into four experimental conditions: the Combined condition, the Influence condition, the Negative Consequences condition and the Control condition. After the experimental manipulation, subjects from each condition had to classify capsules in semi-transparent bottles. Results showed that personal influence is the best predictor of perceived responsibility. Although increased potential negative consequences were sufficient to trigger hesitations, combined influence and negative consequences were necessary to produce modifications. These results are consistent with the results obtained by the questionnaires (e.g. Rhéaume, Ladouceur, Freeston & Letarte, 1995a, Behaviour Research and Therapy, 33, 159-169) and previous manipulations (e.g. Ladouceur et al., 1995).

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

    Midulla, Marco, E-mail: marco.midulla@chru-lille.fr; Moreno, Ramiro, E-mail: ramoroa@gmail.com; Negre-Salvayre, Anne, E-mail: anne.negre-salvayre@inserm.fr

    PurposeAlthough the widespread acceptance of thoracic endovascular aortic repair (TEVAR) as a first-line treatment option for a multitude of thoracic aortic diseases, little is known about the consequences of the device implantation on the native aortic anatomy. We propose a comparative analysis of the pre- and postoperative geometry on a clinical series of patients and discuss the potential clinical implicationsMethodsCT pre- and postoperative acquisitions of 30 consecutive patients treated by TEVAR for different pathologies (20 thoracic aortic aneurysms, 6 false aneurysms, 3 penetrating ulcers, 1 traumatic rupture) were used to model the vascular geometry. Pre- and postoperative geometries were comparedmore » for each patient by pairing and matching the 3D models. An implantation site was identified, and focal differences were detected and described.ResultsSegmentation of the data sets was successfully performed for all 30 subjects. Geometry differences between the pre- and postoperative meshes were depicted in 23 patients (76 %). Modifications at the upper implantation site were detected in 14 patients (47 %), and among them, the implantation site involved the arch (Z0–3) in 11 (78 %).ConclusionModeling the vascular geometry on the basis of imaging data offers an effective tool to perform patient-specific analysis of the vascular geometry before and after the treatment. Future studies will evaluate the consequences of these changes on the aortic function.« less

  1. Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health

    PubMed Central

    Herndon, J. Marvin

    2015-01-01

    The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un-leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction. PMID:26270671

  2. Body piercing with fatal consequences.

    PubMed

    Ranga, N; Jeffery, A J

    2011-01-25

    Body modifications such as piercings, tattoos and surgery have increased in popularity in recent times and have become more socially acceptable. The common complications of piercing different parts of the human anatomy are well-documented, including sepsis, allergic reactions and, more rarely, endocarditis and ischaemia. Deaths related to piercing complications are primarily septic in origin. In this case, a man in his 50s died due to complications of his multiple umbilical piercings. The cause of death was unusually linked to body modification; the umbilical piercings had ultimately led to a mesenteric infarction. Cases such as these are forensically important due to potential manslaughter charges that could be brought against a piercing establishment. More importantly, this case highlights another extreme complication of body modification. Fashion statements are always changing and impact upon many lives. It is important to highlight to people the potentially life-threatening complications of common piercing practices.

  3. Government Ownership Restrictions and Efficiency: The Case of the FCC's Dupoply Rule.

    ERIC Educational Resources Information Center

    Anderson, Keith B.; Woodbury, John R.

    Recently the Federal Communications Commission (FCC) has been considering modifications to its regulations governing local and national media ownership and has indicated more interest in the efficiency consequences of the regulations, including those that might arise from common ownership of multiple radio stations. This paper seeks to determine…

  4. Glutaredoxin GrxC2 catalyzes the glutathionylation and inactivation of Arabidopsis BRI1-ASSOCIATED RECEPTOR-LIKE KINASE 1 (BAK1) in vitro

    USDA-ARS?s Scientific Manuscript database

    Reversible protein phosphorylation, catalyzed by protein kinases, is the most widely studied post-translational modification (PTM) both in terms of its occurrence and the regulatory consequences of phosphorylation events on phosphorylated proteins. In addition to reversible phosphorylation, many pro...

  5. Line intersect sampling: Ell-shaped transects and multiple intersections

    Treesearch

    Timothy G. Gregoire; Harry T. Valentine

    2003-01-01

    The probability of selecting a population element under line intersect sampling depends on the width of the particle in the direction perpendicular to the transect, as is well known. The consequence of this when using ell-shaped transects rather than straight-line transects are explicated, and modifications that preserve design-unbiasedness of Kaiser's (1983)...

  6. 76 FR 58094 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-20

    ... subsequent Eddy Current inspection (NDI) [non-destructive inspection] of the same area to detect cracks... inspections are eddy current inspections. The modification includes cold expansion of the former lower wing... with consequent loss of control. * * * * * The new inspections are eddy current inspections. The...

  7. Methyltransferases acquired by lactococcal 936-type phage provide protection against restriction endonuclease activity.

    PubMed

    Murphy, James; Klumpp, Jochen; Mahony, Jennifer; O'Connell-Motherway, Mary; Nauta, Arjen; van Sinderen, Douwe

    2014-10-01

    So-called 936-type phages are among the most frequently isolated phages in dairy facilities utilising Lactococcus lactis starter cultures. Despite extensive efforts to control phage proliferation and decades of research, these phages continue to negatively impact cheese production in terms of the final product quality and consequently, monetary return. Whole genome sequencing and in silico analysis of three 936-type phage genomes identified several putative (orphan) methyltransferase (MTase)-encoding genes located within the packaging and replication regions of the genome. Utilising SMRT sequencing, methylome analysis was performed on all three phages, allowing the identification of adenine modifications consistent with N-6 methyladenine sequence methylation, which in some cases could be attributed to these phage-encoded MTases. Heterologous gene expression revealed that M.Phi145I/M.Phi93I and M.Phi93DAM, encoded by genes located within the packaging module, provide protection against the restriction enzymes HphI and DpnII, respectively, representing the first functional MTases identified in members of 936-type phages. SMRT sequencing technology enabled the identification of the target motifs of MTases encoded by the genomes of three lytic 936-type phages and these MTases represent the first functional MTases identified in this species of phage. The presence of these MTase-encoding genes on 936-type phage genomes is assumed to represent an adaptive response to circumvent host encoded restriction-modification systems thereby increasing the fitness of the phages in a dynamic dairy environment.

  8. Bayesian Factor Analysis as a Variable Selection Problem: Alternative Priors and Consequences

    PubMed Central

    Lu, Zhao-Hua; Chow, Sy-Miin; Loken, Eric

    2016-01-01

    Factor analysis is a popular statistical technique for multivariate data analysis. Developments in the structural equation modeling framework have enabled the use of hybrid confirmatory/exploratory approaches in which factor loading structures can be explored relatively flexibly within a confirmatory factor analysis (CFA) framework. Recently, a Bayesian structural equation modeling (BSEM) approach (Muthén & Asparouhov, 2012) has been proposed as a way to explore the presence of cross-loadings in CFA models. We show that the issue of determining factor loading patterns may be formulated as a Bayesian variable selection problem in which Muthén and Asparouhov’s approach can be regarded as a BSEM approach with ridge regression prior (BSEM-RP). We propose another Bayesian approach, denoted herein as the Bayesian structural equation modeling with spike and slab prior (BSEM-SSP), which serves as a one-stage alternative to the BSEM-RP. We review the theoretical advantages and disadvantages of both approaches and compare their empirical performance relative to two modification indices-based approaches and exploratory factor analysis with target rotation. A teacher stress scale data set (Byrne, 2012; Pettegrew & Wolf, 1982) is used to demonstrate our approach. PMID:27314566

  9. Redox proteomics for the assessment of redox-related posttranslational regulation in plants.

    PubMed

    Mock, Hans-Peter; Dietz, Karl-Josef

    2016-08-01

    The methodological developments of in vivo and in vitro protein labeling and subsequent detection enable sensitive and specific detection of redox modifications. Such methods are presently applied to diverse cells and tissues, subproteomes and developmental as well as environmental conditions. The chloroplast proteome is particularly suitable for such kind of studies, because redox regulation of chloroplast proteins is well established, many plastid proteins are abundant, redox network components have been inventoried in great depth, and functional consequences explored. Thus the repertoire of redox-related posttranslational modifications on the one hand side and their abundance on the other pose a challenge for the near future to understand their contribution to physiological regulation. The various posttranslational redox modifications are introduced, followed by a description of the available proteomics methods. The significance of the redox-related posttranslational modification is exemplarily worked out using established examples from photosynthesis. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. Copyright © 2016. Published by Elsevier B.V.

  10. Modify the Histone to Win the Battle: Chromatin Dynamics in Plant–Pathogen Interactions

    PubMed Central

    Ramirez-Prado, Juan S.; Piquerez, Sophie J. M.; Bendahmane, Abdelhafid; Hirt, Heribert; Raynaud, Cécile; Benhamed, Moussa

    2018-01-01

    Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant–pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses. Herein, we review the state of the art in the epigenomic aspects of plant immunity, focusing on chromatin modifications, chromatin modifiers, and their physiological consequences. In addition, we explore the exciting field of understanding how plant pathogens have adapted to manipulate the plant epigenomic regulation in order to weaken their immune system and thrive in their host, as well as how histone modifications in eukaryotic pathogens are involved in the regulation of their virulence. PMID:29616066

  11. Covalent modifications of the amyloid beta peptide by hydroxynonenal: Effects on metal ion binding by monomers and insights into the fibril topology.

    PubMed

    Grasso, G; Komatsu, H; Axelsen, P H

    2017-09-01

    Amyloid β peptides (Aβ) and metal ions are associated with oxidative stress in Alzheimer's disease (AD). Oxidative stress, acting on ω-6 polyunsaturated fatty acyl chains, produces diverse products, including 4-hydroxy-2-nonenal (HNE), which can covalently modify the Aβ that helped to produce it. To examine possible feedback mechanisms involving Aβ, metal ions and HNE production, the effects of HNE modification and fibril formation on metal ion binding was investigated. Results indicate that copper(II) generally inhibits the modification of His side chains in Aβ by HNE, but that once modified, copper(II) still binds to Aβ with high affinity. Fibril formation protects only one of the three His residues in Aβ from HNE modification, and this protection is consistent with proposed models of fibril structure. These results provide insight into a network of biochemical reactions that may be operating as a consequence of oxidative stress in AD, or as part of the pathogenic process. Copyright © 2016. Published by Elsevier Inc.

  12. Tablet compression tooling - Impact of punch face edge modification.

    PubMed

    Anbalagan, Parthiban; Heng, Paul Wan Sia; Liew, Celine Valeria

    2017-05-30

    The influence of punch face edge geometry modification on tablet compression and the properties of the resultant tablets produced on a rotary press were investigated. The results revealed that tablets produced from the punches with radius edge face geometry consistently displayed better physical quality; higher tensile strength and lower capping tendency. Modification of the angled edge of the bevel face to the curved edge of the radius face, enabled deeper punch penetration in the die cavity during the compression cycle, bringing about greater compact densification. Improved die fill packing increased interparticulate bond formation and helped to dissipate destructive elasticity within the compact, consequently reduced tablet expansion during the decompression phase. The positive impact of punch face edge modification was also more noticeable at a higher turret speed. The application of the precompression force along with dwell time extension amplified the tableting performance of radius edge punch face design to a greater extent when compared to bevel edge punch face design. This could be attributed to the enhanced packing efficiency at both precompression and main compression stages. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers.

    PubMed

    Madsen, Ida E H; Lange, Theis; Borritz, Marianne; Rugulies, Reiner

    2015-06-01

    Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout. We used questionnaire data from a three-wave study of Danish human service workers conducted during 1999-2005, linked with national register data on purchases of antidepressants (ATC: N06A). We included 4788 observations from 2936 individuals (81% women) and analysed data by Aalens additive hazards modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted antidepressant treatment. This association was modified by sex (p < 0.01). In men, high vs. intermediate burnout was associated with a 5% increased risk of antidepressant treatment per year of follow-up. This risk difference was 1% for women. Due to the sex specific patterns, we restricted effect modification analyses to women. We found no effect-modification by the examined work environment factors, though a sensitivity analysis indicated a possible stronger association in women of lower occupational position. In conclusion, burnout predicted antidepressant treatment, with a stronger association in men than women. We found no evidence of effect-modification by any of the examined psychosocial work environment factors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Ras-Induced Changes in H3K27me3 Occur after Those in Transcriptional Activity

    PubMed Central

    Hosogane, Masaki; Funayama, Ryo; Nishida, Yuichiro; Nagashima, Takeshi; Nakayama, Keiko

    2013-01-01

    Oncogenic signaling pathways regulate gene expression in part through epigenetic modification of chromatin including DNA methylation and histone modification. Trimethylation of histone H3 at lysine-27 (H3K27), which correlates with transcriptional repression, is regulated by an oncogenic form of the small GTPase Ras. Although accumulation of trimethylated H3K27 (H3K27me3) has been implicated in transcriptional regulation, it remains unclear whether Ras-induced changes in H3K27me3 are a trigger for or a consequence of changes in transcriptional activity. We have now examined the relation between H3K27 trimethylation and transcriptional regulation by Ras. Genome-wide analysis of H3K27me3 distribution and transcription at various times after expression of oncogenic Ras in mouse NIH 3T3 cells identified 115 genes for which H3K27me3 level at the gene body and transcription were both regulated by Ras. Similarly, 196 genes showed Ras-induced changes in transcription and H3K27me3 level in the region around the transcription start site. The Ras-induced changes in transcription occurred before those in H3K27me3 at the genome-wide level, a finding that was validated by analysis of individual genes. Depletion of H3K27me3 either before or after activation of Ras signaling did not affect the transcriptional regulation of these genes. Furthermore, given that H3K27me3 enrichment was dependent on Ras signaling, neither it nor transcriptional repression was maintained after inactivation of such signaling. Unexpectedly, we detected unannotated transcripts derived from intergenic regions at which the H3K27me3 level is regulated by Ras, with the changes in transcript abundance again preceding those in H3K27me3. Our results thus indicate that changes in H3K27me3 level in the gene body or in the region around the transcription start site are not a trigger for, but rather a consequence of, changes in transcriptional activity. PMID:24009517

  15. Commensurate Priors for Incorporating Historical Information in Clinical Trials Using General and Generalized Linear Models

    PubMed Central

    Hobbs, Brian P.; Sargent, Daniel J.; Carlin, Bradley P.

    2014-01-01

    Assessing between-study variability in the context of conventional random-effects meta-analysis is notoriously difficult when incorporating data from only a small number of historical studies. In order to borrow strength, historical and current data are often assumed to be fully homogeneous, but this can have drastic consequences for power and Type I error if the historical information is biased. In this paper, we propose empirical and fully Bayesian modifications of the commensurate prior model (Hobbs et al., 2011) extending Pocock (1976), and evaluate their frequentist and Bayesian properties for incorporating patient-level historical data using general and generalized linear mixed regression models. Our proposed commensurate prior models lead to preposterior admissible estimators that facilitate alternative bias-variance trade-offs than those offered by pre-existing methodologies for incorporating historical data from a small number of historical studies. We also provide a sample analysis of a colon cancer trial comparing time-to-disease progression using a Weibull regression model. PMID:24795786

  16. Effective Cross Section of Cold Formed Steel Column Under Axial Compression

    NASA Astrophysics Data System (ADS)

    Manikandan, P.; Pradeep, T.

    2018-06-01

    The compressive resistance of cold-formed steel (CFS) section may be governed by local, distortional or overall buckling and any apparent interaction between these modes. A new inventive stiffened CFS section is elected in this study, selected cross sections geometries and lengths are chosen such that all the types of buckling modes are met with. Buckling plot is plotted using linear elastic buckling analysis software (CUFSM). Using the test results obtained in the literature, the developed finite element model is calibrated and furthers a total of 126 parametric study is conducted such as a consequence of dimensions and the length of the cross section, thickness and yield stress. The FEA included relevant material and geometric imperfections. All the columns are analyzed under pin end conditions with axial compression. The analysis results demonstrate that the DSM equations generally assess the strength of stiffened section conservatively. Modifications to the DSM equations are recommended to evaluate the strength of stiffened section more precisely.

  17. Effect of nutrition education and diet modification in iron depleted preschool children in nurseries in Tehran: a pilot study.

    PubMed

    Khoshnevisan, Farnaz; Kimiagar, Masood; Kalantaree, Nasser; Valaee, Nasser; Shaheedee, Nooshin

    2004-07-01

    In view of the high prevalence of iron deficiency in preschool children and its consequences, this study was carried out to examine the effect of nutrition education and dietary modification on 438 two- to six-year-old nursery school children in Tehran in 1999. Sixty-two children who were judged anemic, iron-depleted, or having low iron stores were randomly allocated to "control," "dietary modification" (consuming one additional citrus fruit after lunch), and "nutrition education" (teaching the mothers proper eating patterns based on the food pyramid) groups. Food habits were surveyed, including 24-hour dietary recall and food frequency, as well as timing of consumption of special items; this survey was carried out for each child before and after intervention. After three months, blood samples were taken from the subjects. The prevalence of anemia, iron depletion, and low iron stores was 11.4, 62.8, and 15.1% respectively, with no significant differences observed in hemoglobin and percent transferrin saturation (%TS) between the groups. Mean+/-SD serum ferritin concentrations in "control," "diet modification," and "nutrition education" groups were 8.9+/-3.1, 9.5+/-3.7, and 6.9+/-2.3 microg/dL. The same figures at the end of intervention were 6.9+/-3.5, 11.2+/-5, and 10.7+/-5.9 microg/dL, respectively. Analysis of variance showed ferritin concentrations to be significantly different, in that there was a reduction in the control and elevation in the nutrition education groups. There was no significant difference in %TS before and after the intervention. During three months of intervention, changes in frequency of fruit and fruit juice intake after the meals in nutrition education and diet modification groups were significantly correlated to serum ferritin alteration. Frequency of fruit juice intake (rich in vitamin C) after meals (at least five times a week) can significantly increase serum ferritin within three months. Therefore, educating mothers of iron-deficient children while increasing the iron stores in children can prevent the recurrence of iron deficiency and result in general child well-being.

  18. Modification of orthogonal tRNAs: unexpected consequences for sense codon reassignment.

    PubMed

    Biddle, Wil; Schmitt, Margaret A; Fisk, John D

    2016-12-01

    Breaking the degeneracy of the genetic code via sense codon reassignment has emerged as a way to incorporate multiple copies of multiple non-canonical amino acids into a protein of interest. Here, we report the modification of a normally orthogonal tRNA by a host enzyme and show that this adventitious modification has a direct impact on the activity of the orthogonal tRNA in translation. We observed nearly equal decoding of both histidine codons, CAU and CAC, by an engineered orthogonal M. jannaschii tRNA with an AUG anticodon: tRNA Opt We suspected a modification of the tRNA Opt AUG anticodon was responsible for the anomalous lack of codon discrimination and demonstrate that adenosine 34 of tRNA Opt AUG is converted to inosine. We identified tRNA Opt AUG anticodon loop variants that increase reassignment of the histidine CAU codon, decrease incorporation in response to the histidine CAC codon, and improve cell health and growth profiles. Recognizing tRNA modification as both a potential pitfall and avenue of directed alteration will be important as the field of genetic code engineering continues to infiltrate the genetic codes of diverse organisms. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Sleep Modifications in Acute Transient Global Amnesia

    PubMed Central

    Della Marca, Giacomo; Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Broccolini, Aldobrando; Frisullo, Giovanni; Marano, Giuseppe; Morosetti, Roberta; Pilato, Fabio; Profice, Paolo; Vollono, Catello; Di Lazzaro, Vincenzo

    2013-01-01

    Study Objective: Transient global amnesia (TGA) is a temporary memory loss characterized by an abrupt onset of antero-grade and retrograde amnesia, totally reversible. Since sleep plays a major role in memory consolidation, and in the storage of memory-related traces into the brain cortex, the aims of the present study were: (1) to evaluate changes in sleep macro-structure in TGA; (2) to assess modifications in sleep micro-structure in TGA, with particular reference to the arousal EEG and to cyclic alternating pattern (CAP); (3) to compare sleep parameters in TGA patients with a control group of patients with acute ischemic events (“minor stroke” or transient ischemic attack [TIA]) clinically and neuroradiologically “similar” to the TGA. Methods: TGA group: 17 patients, (8 men and 9 women, 60.2 ± 12.5 years). Stroke or TIA (SoT) group: 17 patients hospitalized in the Stroke Unit for recent onset of minor stroke or TIA with hemispheric localization; healthy controls (HC) group: 17 healthy volunteers, matched for age and sex. Patients and controls underwent full-night polysomnography. Results: In the multivariate analysis (conditions TGA, SoT, and HC) a significant effect of the condition was observed for sleep efficiency index, number of awakenings longer 1 min, REM latency, CAP time, and CAP rate. TGA and SoT differed only for CAP time and CAP rate, which were lower in the TGA group. Conclusions: Microstructural modification associated with TGA could be consequent to: (1) hippocampal dysfunction and memory impairment; (2) impairment of arousal-related structures (in particular, cholinergic pathways); (3) emotional distress. Citation: Della Marca G; Mazza M; Losurdo A; Testani E; Broccolini A; Frisullo G; Marano G; Morosetti R; Pilato F; Profice P; Vollono C; Di Lazzaro V. Sleep modifications in acute transient global amnesia. J Clin Sleep Med 2013;9(9):921-927. PMID:23997704

  20. Polyclonal antithymocyte globulin and cardiovascular disease in kidney transplant recipients.

    PubMed

    Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

    2014-06-01

    T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. Copyright © 2014 by the American Society of Nephrology.

  1. Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

    PubMed Central

    Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

    2014-01-01

    T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)–induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8+ T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. PMID:24511120

  2. A morphospace for reef fishes: elongation is the dominant axis of body shape evolution.

    PubMed

    Claverie, Thomas; Wainwright, Peter C

    2014-01-01

    Tropical reef fishes are widely regarded as being perhaps the most morphologically diverse vertebrate assemblage on earth, yet much remains to be discovered about the scope and patterns of this diversity. We created a morphospace of 2,939 species spanning 56 families of tropical Indo-Pacific reef fishes and established the primary axes of body shape variation, the phylogenetic consistency of these patterns, and whether dominant patterns of shape change can be accomplished by diverse underlying changes. Principal component analysis showed a major axis of shape variation that contrasts deep-bodied species with slender, elongate forms. Furthermore, using custom methods to compare the elongation vector (axis that maximizes elongation deformation) and the main vector of shape variation (first principal component) for each family in the morphospace, we showed that two thirds of the families diversify along an axis of body elongation. Finally, a comparative analysis using a principal coordinate analysis based on the angles among first principal component vectors of each family shape showed that families accomplish changes in elongation with a wide range of underlying modifications. Some groups such as Pomacentridae and Lethrinidae undergo decreases in body depth with proportional increases in all body regions, while other families show disproportionate changes in the length of the head (e.g., Labridae), the trunk or caudal region in all combinations (e.g., Pempheridae and Pinguipedidae). In conclusion, we found that evolutionary changes in body shape along an axis of elongation dominates diversification in reef fishes. Changes in shape on this axis are thought to have immediate implications for swimming performance, defense from gape limited predators, suction feeding performance and access to some highly specialized habitats. The morphological modifications that underlie changes in elongation are highly diverse, suggesting a role for a range of developmental processes and functional consequences.

  3. Suggestion for the Implementation of the Bologna Declaration in Hungary in Engineering Higher Education

    ERIC Educational Resources Information Center

    Molnar, Karoly; Jobbagy, Akos

    2004-01-01

    The countries that signed the Bologna Declaration need also to modify their engineering programmes accordingly. In Hungary some modifications are necessary independently of the Bologna Declaration. The number of students has increased by a factor of three during the past decade without an increase in the number of staff. The consequence is…

  4. Shapes of cometary isophotes with Maxwellian distribution of initial velocities for neutral molecules

    NASA Astrophysics Data System (ADS)

    Žáček, P.; Wolf, M.

    2017-10-01

    This paper contains necessary modification of Bessel's equations for the axial cometary syndyne. This correction provides the accurate values of molecular acceleration in a cometary tail and precise values of decay constants for radiating molecules and their lifetimes. In consequence the hypothesis of the predissociation of molecules seems to be useless.

  5. The interaction of the soybean seed high oleic acid oil trait with other fatty acid modifications

    USDA-ARS?s Scientific Manuscript database

    Oil value is determined by the functional qualities imparted from the fatty acid profile. Soybean oil historically had excellent utilization in both food and industrial uses, but the need to increase the stability of the oil without negative health consequences has led to a significant decline in s...

  6. Impact of chevron spacing and asymmetric distribution on supersonic jet acoustics and flow

    NASA Astrophysics Data System (ADS)

    Heeb, N.; Gutmark, E.; Kailasanath, K.

    2016-05-01

    An experimental investigation into the effect of chevron spacing and distribution on supersonic jets was performed. Cross-stream and streamwise particle imaging velocimetry measurements were used to relate flow field modification to sound field changes measured by far-field microphones in the overexpanded, ideally expanded, and underexpanded regimes. Drastic modification of the jet cross-section was achieved by the investigated configurations, with both elliptic and triangular shapes attained downstream. Consequently, screech was nearly eliminated with reductions in the range of 10-25 dB depending on the operating condition. Analysis of the streamwise velocity indicated that both the mean shock spacing and strength were reduced resulting in an increase in the broadband shock associated noise spectral peak frequency and a reduction in the amplitude, respectively. Maximum broadband shock associated noise amplitude reductions were in the 5-7 dB range. Chevron proximity was found to be the primary driver of peak vorticity production, though persistence followed the opposite trend. The integrated streamwise vorticity modulus was found to be correlated with peak large scale turbulent mixing noise reduction, though optimal overall sound pressure level reductions did not necessarily follow due to the shock/fine scale mixing noise sources. Optimal large scale mixing noise reductions were in the 5-6 dB range.

  7. Particle imaging velocimetry evaluation of intracranial stents in sidewall aneurysm: hemodynamic transition related to the stent design.

    PubMed

    Bouillot, Pierre; Brina, Olivier; Ouared, Rafik; Lovblad, Karl-Olof; Farhat, Mohamed; Pereira, Vitor Mendes

    2014-01-01

    We investigated the flow modifications induced by a large panel of commercial-off-the-shelf (COTS) intracranial stents in an idealized sidewall intracranial aneurysm (IA). Flow velocities in IA silicone model were assessed with and without stent implantation using particle imaging velocimetry (PIV). The use of the recently developed multi-time-lag method has allowed for uniform and precise measurements of both high and low velocities at IA neck and dome, respectively. Flow modification analysis of both regular (RSs) and flow diverter stents (FDSs) was subsequently correlated with relevant geometrical stent parameters. Flow reduction was found to be highly sensitive to stent porosity variations for regular stents RSs and moderately sensitive for FDSs. Consequently, two distinct IA flow change trends, with velocity reductions up to 50% and 90%, were identified for high-porosity RS and low-porosity FDS, respectively. The intermediate porosity (88%) regular braided stent provided the limit at which the transition in flow change trend occurred with a flow reduction of 84%. This transition occurred with decreasing stent porosity, as the driving force in IA neck changed from shear stress to differential pressure. Therefore, these results suggest that stents with intermediate porosities could possibly provide similar flow change patterns to FDS, favourable to curative thrombogenesis in IAs.

  8. Difficulties in Generating Specific Antibodies for Immunohistochemical Detection of Nitrosylated Tubulins

    PubMed Central

    Kamnev, Anton; Muhar, Matthias; Preinreich, Martina; Ammer, Hermann; Propst, Friedrich

    2013-01-01

    Protein S-nitrosylation, the covalent attachment of a nitroso moiety to thiol groups of specific cysteine residues, is one of the major pathways of nitric oxide signaling. Hundreds of proteins are subject to this transient post-translational modification and for some the functional consequences have been identified. Biochemical assays for the analysis of protein S-nitrosylation have been established and can be used to study if and under what conditions a given protein is S-nitrosylated. In contrast, the equally desirable subcellular localization of specific S-nitrosylated protein isoforms has not been achieved to date. In the current study we attempted to specifically localize S-nitrosylated α- and β-tubulin isoforms in primary neurons after fixation. The approach was based on in situ replacement of the labile cysteine nitroso modification with a stable tag and the subsequent use of antibodies which recognize the tag in the context of the tubulin polypeptide sequence flanking the cysteine residue of interest. We established a procedure for tagging S-nitrosylated proteins in cultured primary neurons and obtained polyclonal anti-tag antibodies capable of specifically detecting tagged proteins on immunoblots and in fixed cells. However, the antibodies were not specific for tubulin isoforms. We suggest that different tagging strategies or alternative methods such as fluorescence resonance energy transfer techniques might be more successful. PMID:23840827

  9. Application of the Bethesda System for Reporting Thyroid Cytopathology in the Eastern Province of Saudi Arabia: A Follow-Up Study.

    PubMed

    Alabdulqader, Noof A; Shareef, Sameera Q; Ali, Jassim A; Yousef, Mohammad M; Al-Abbadi, Mousa A

    2015-01-01

    This is a follow-up study to our previous analysis of thyroid aspirates utilizing the Bethesda System for Reporting Thyroid Cytology (BSRTC). The same study design was utilized for 2 years comparing 2 periods. A total of 251 thyroid aspirates from 218 patients were reviewed and deemed comparable to the previous cohort. The variance and consequently the number of interpretations dropped from 26 to 11 with a statistically significant 58% reduction and more consistency. Our unsatisfactory rate dropped from 22 to 10% (reduction of 55%). The risk of malignancy in this follow-up study showed a similar trend: an increase in risk with each step up in the BSRTC categories starting from the 'nondiagnostic' and up to 'malignant'. Few of our benign cases ended up with resection. We noticed sensitivity to the word 'follicular' in this benign category; therefore we propose a modification of the current BSRTC system by omitting the word 'follicular' from the benign category. We strongly believe that this modification harbors no serious damage to the intentions of BSRTC. This follow-up study has shown that the previous awareness campaign about the implementation has worked and can be considered a valid performance improvement program. © 2015 S. Karger AG, Basel.

  10. Generation of novel covalent RNA-protein complexes in cells by ultraviolet B irradiation: implications for autoimmunity.

    PubMed

    Andrade, Felipe; Casciola-Rosen, Livia A; Rosen, Antony

    2005-04-01

    To determine whether ultraviolet B (UVB) irradiation induces novel modifications in autoantigens targeted during experimental photoinduced epidermal damage. To search for novel UVB-induced autoantigen modifications, lysates made from UVB-irradiated human keratinocytes or HeLa cells were immunoblotted using human autoantibodies that recognize ribonucleoprotein autoantigens. Novel autoantigen structures identified were further characterized using nucleases and RNA hybridization. Human sera that recognize U1-70 kd (U1-70K) and La by immunoblotting also recognized multiple novel species when they were used to immunoblot lysates of UVB-irradiated keratinocytes or HeLa cells. These species were not present in control cells and were not observed when apoptosis was induced by Fas ligation or cytotoxic lymphocyte granule contents. Biochemical analysis using multiple assays revealed that these novel UVB-induced molecular species result from the covalent crosslinking between the U1 RNA and the hYRNA molecules with their associated proteins, including U1-70K, La, and likely components of the Sm particle. These data demonstrate that UVB irradiation of live cells can directly induce covalent RNA-protein complexes, which are recognized by human autoantibodies. As previously described for other autoantigens, these covalent complexes of RNA and proteins may have important consequences in terms of antigen capture and processing.

  11. Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction.

    PubMed

    Cribbs, Adam P; Perera, Sumeth M W

    2017-12-01

    Since its emergence in 2012, the genome editing technique known as CRISPR-Cas9 and its scientific use have rapidly expanded globally within a very short period of time. The technique consists of using an RNA guide molecule to bind to complementary DNA sequences, which simultaneously recruits the endonuclease Cas9 to introduce double-stranded breaks in the target DNA. The resulting double-stranded break is then repaired, allowing modification or removal of specific DNA bases. The technique has gained momentum in the laboratory because it is cheap, quick, and easy to use. Moreover, it is also being applied in vivo to generate more complex animal model systems. Such use of genome editing has proven to be highly effective and warrants a potential therapy for both genetic and non-genetic diseases. Although genome editing has the potential to be a transformative therapy for patients it is still in its infancy. Consequently, the legal and ethical frameworks are yet to be fully discussed and will be an increasingly important topic as the technology moves towards more contentious issues such as modification of the germline. Here, we review a number of scientific and ethical issues which may potentially influence the development of both the technology and its use in the clinical setting.

  12. SUMO1 Affects Synaptic Function, Spine Density and Memory

    PubMed Central

    Matsuzaki, Shinsuke; Lee, Linda; Knock, Erin; Srikumar, Tharan; Sakurai, Mikako; Hazrati, Lili-Naz; Katayama, Taiichi; Staniszewski, Agnieszka; Raught, Brian; Arancio, Ottavio; Fraser, Paul E.

    2015-01-01

    Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration. PMID:26022678

  13. Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction


    PubMed Central

    Cribbs, Adam P.; Perera, Sumeth M. W.

    2017-01-01

    Since its emergence in 2012, the genome editing technique known as CRISPR-Cas9 and its scientific use have rapidly expanded globally within a very short period of time. The technique consists of using an RNA guide molecule to bind to complementary DNA sequences, which simultaneously recruits the endonuclease Cas9 to introduce double-stranded breaks in the target DNA. The resulting double-stranded break is then repaired, allowing modification or removal of specific DNA bases. The technique has gained momentum in the laboratory because it is cheap, quick, and easy to use. Moreover, it is also being applied in vivo to generate more complex animal model systems. Such use of genome editing has proven to be highly effective and warrants a potential therapy for both genetic and non-genetic diseases. Although genome editing has the potential to be a transformative therapy for patients it is still in its infancy. Consequently, the legal and ethical frameworks are yet to be fully discussed and will be an increasingly important topic as the technology moves towards more contentious issues such as modification of the germline. Here, we review a number of scientific and ethical issues which may potentially influence the development of both the technology and its use in the clinical setting. PMID:29259526

  14. Reduced fitness of Atlantic salmon released in the wild after one generation of captive breeding

    PubMed Central

    Milot, Emmanuel; Perrier, Charles; Papillon, Lucie; Dodson, Julian J; Bernatchez, Louis

    2013-01-01

    Salmonids rank among the most socioeconomically valuable fishes and the most targeted species by stocking with hatchery-reared individuals. Here, we used molecular parentage analysis to assess the reproductive success of wild- and hatchery-born Atlantic salmon over three consecutive years in a small river in Québec. Yearly restocking in this river follows a single generation of captive breeding. Among the adults returning to the river to spawn, between 11% and 41% each year were born in hatchery. Their relative reproductive success (RRS) was nearly half that of wild-born fish (0.55). RRS varied with life stage, being 0.71 for fish released at the fry stage and 0.42 for fish released as smolt. The lower reproductive success of salmon released as smolt was partly mediated by the modification of the proportion of single-sea-winter/multi-sea-winter fish. Overall, our results suggest that modifications in survival and growth rates alter the life-history strategies of these fish at the cost of their reproductive success. Our results underline the potential fitness decrease, warn on long-term evolutionary consequences for the population of repeated stocking and support the adoption of more natural rearing conditions for captive juveniles and their release at a younger stage, such as unfed fry. PMID:23745139

  15. Variable two-crystal cascade for conical refraction.

    PubMed

    Peet, V

    2015-05-15

    The cascade conical refraction occurs when a collimated light beam is passed consequently along the optic axes of several biaxial crystals arranged in a series. For commonly used optical arrangements, the general structure of light emerging from such a cascade is rigorously determined by the used crystals, leaving few possibilities for the variations of the established light pattern. A simple modification of a two-crystal arrangement where one of the two crystals is placed beyond the imaging lens is reported. This modification adds an extreme versatility to the effect and allows one to tune continuously the actual cascade parameters. As a result, practically any pattern of two-crystal cascade conical refraction can be obtained for any pair of biaxial crystals.

  16. The physics of cancer: The role of epigenetics and chromosome conformation in cancer progression

    NASA Astrophysics Data System (ADS)

    Naimark, Oleg B.; Nikitiuk, Aleksandr S.; Baudement, Marie-Odile; Forné, Thierry; Lesne, Annick

    2016-08-01

    Cancer progression is generally described in terms of accumulated genetic alterations and ensuing changes in cell properties. However, intermediary modifications are involved in the establishment of cancer cell phenotypes, at different levels of nuclear organization: DNA damages and their structural consequences, epigenetic modifications and their impact on chromatin architecture, changes in chromosome 3D organization. We review some of these alterations with a focus on their physical aspects. The challenge is to understand the multiscale interplay between generic physical mechanisms and specific biological factors in cancer cells. We argue that such an interdisciplinary perspective offers a novel viewpoint on cancer progression, early diagnosis and possibly therapeutic targets.

  17. The Influence of Chemical Modification on Linker Rotational Dynamics in Metal-Organic Frameworks.

    PubMed

    Damron, Joshua T; Ma, Jialiu; Kurz, Ricardo; Saalwächter, Kay; Matzger, Adam J; Ramamoorthy, Ayyalusamy

    2018-05-21

    The robust synthetic flexibility of metal-organic frameworks (MOFs) offers a promising class of tailorable materials, for which the ability to tune specific physicochemical properties is highly desired. This is achievable only through a thorough description of the consequences for chemical manipulations both in structure and dynamics. Magic angle spinning solid-state NMR spectroscopy offers many modalities in this pursuit, particularly for dynamic studies. Herein, we employ a separated-local-field NMR approach to show how specific intraframework chemical modifications to MOF UiO-66 heavily modulate the dynamic evolution of the organic ring moiety over several orders of magnitude. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. The control of satellites with microgravity constraints: The COMET Control System

    NASA Astrophysics Data System (ADS)

    Grossman, Walter; Freesland, Douglas

    1994-05-01

    The COMET attitude determination and control system, using inverse dynamics and a novel torque distribution/momentum management technique, has shown great flexibility, performance, and robustness. Three-axis control with two wheels is an inherent consequence of inverse dynamics control which allows for reduction in spacecraft weight and cost, or alternatively, provides a simple means of failure-redundancy for three-wheel spacecraft. The control system, without modification, has continued to perform well in spite of large changes in spacecraft mass properties and mission orbit altitude that have occurred during development. This flexibility has obviated imposition of early stringent ADACS design constraints and has greatly reduced commonly incurred ADACS modification costs and delay associated with program maturation.

  19. The control of satellites with microgravity constraints: The COMET Control System

    NASA Technical Reports Server (NTRS)

    Grossman, Walter; Freesland, Douglas

    1994-01-01

    The COMET attitude determination and control system, using inverse dynamics and a novel torque distribution/momentum management technique, has shown great flexibility, performance, and robustness. Three-axis control with two wheels is an inherent consequence of inverse dynamics control which allows for reduction in spacecraft weight and cost, or alternatively, provides a simple means of failure-redundancy for three-wheel spacecraft. The control system, without modification, has continued to perform well in spite of large changes in spacecraft mass properties and mission orbit altitude that have occurred during development. This flexibility has obviated imposition of early stringent ADACS design constraints and has greatly reduced commonly incurred ADACS modification costs and delay associated with program maturation.

  20. The physics of cancer: The role of epigenetics and chromosome conformation in cancer progression

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

    Naimark, Oleg B.; Nikitiuk, Aleksandr S.; Baudement, Marie-Odile

    Cancer progression is generally described in terms of accumulated genetic alterations and ensuing changes in cell properties. However, intermediary modifications are involved in the establishment of cancer cell phenotypes, at different levels of nuclear organization: DNA damages and their structural consequences, epigenetic modifications and their impact on chromatin architecture, changes in chromosome 3D organization. We review some of these alterations with a focus on their physical aspects. The challenge is to understand the multiscale interplay between generic physical mechanisms and specific biological factors in cancer cells. We argue that such an interdisciplinary perspective offers a novel viewpoint on cancer progression,more » early diagnosis and possibly therapeutic targets.« less

  1. 77 FR 65506 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-29

    ...We propose to supersede an existing airworthiness directive (AD) that applies to certain The Boeing Company Model 757-200 and - 200PF series airplanes. The existing AD currently requires modification of the nacelle strut and wing structure, and repair of any damage found during the modification. Since we issued that AD, a compliance time error involving the optional threshold formula was discovered, which could allow an airplane to exceed the acceptable compliance time for addressing the unsafe condition. This proposed AD would specify a maximum compliance time limit that overrides the optional threshold formula results. We are proposing this AD to prevent fatigue cracking in primary strut structure and consequent reduced structural integrity of the strut.

  2. Computational insights into charge transfer across functionalized semiconductor surfaces

    NASA Astrophysics Data System (ADS)

    Kearney, Kara; Rockett, Angus; Ertekin, Elif

    2017-12-01

    Photoelectrochemical water-splitting is a promising carbon-free fuel production method for producing H2 and O2 gas from liquid water. These cells are typically composed of at least one semiconductor photoelectrode which is prone to degradation and/or oxidation. Various surface modifications are known for stabilizing semiconductor photoelectrodes, yet stabilization techniques are often accompanied by a decrease in photoelectrode performance. However, the impact of surface modification on charge transport and its consequence on performance is still lacking, creating a roadblock for further improvements. In this review, we discuss how density functional theory and finite-element device simulations are reliable tools for providing insight into charge transport across modified photoelectrodes.

  3. Ecological Effects of Weather Modification: A Problem Analysis.

    ERIC Educational Resources Information Center

    Cooper, Charles F.; Jolly, William C.

    This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

  4. From a 2DE-gel spot to protein function: lesson learned from HS1 in chronic lymphocytic leukemia.

    PubMed

    Apollonio, Benedetta; Bertilaccio, Maria Teresa Sabrina; Restuccia, Umberto; Ranghetti, Pamela; Barbaglio, Federica; Ghia, Paolo; Caligaris-Cappio, Federico; Scielzo, Cristina

    2014-10-19

    The identification of molecules involved in tumor initiation and progression is fundamental for understanding disease's biology and, as a consequence, for the clinical management of patients. In the present work we will describe an optimized proteomic approach for the identification of molecules involved in the progression of Chronic Lymphocytic Leukemia (CLL). In detail, leukemic cell lysates are resolved by 2-dimensional Electrophoresis (2DE) and visualized as "spots" on the 2DE gels. Comparative analysis of proteomic maps allows the identification of differentially expressed proteins (in terms of abundance and post-translational modifications) that are picked, isolated and identified by Mass Spectrometry (MS). The biological function of the identified candidates can be tested by different assays (i.e. migration, adhesion and F-actin polymerization), that we have optimized for primary leukemic cells.

  5. Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics.

    PubMed

    Arampatzis, Georgios; Katsoulakis, Markos A; Rey-Bellet, Luc

    2016-03-14

    We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systems with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.

  6. Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics

    NASA Astrophysics Data System (ADS)

    Arampatzis, Georgios; Katsoulakis, Markos A.; Rey-Bellet, Luc

    2016-03-01

    We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systems with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.

  7. Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics

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

    Arampatzis, Georgios; Katsoulakis, Markos A.; Rey-Bellet, Luc

    2016-03-14

    We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systemsmore » with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.« less

  8. Forty Years of Ebolavirus Molecular Biology: Understanding a Novel Disease Agent Through the Development and Application of New Technologies.

    PubMed

    Groseth, Allison; Hoenen, Thomas

    2017-01-01

    Molecular biology is a broad discipline that seeks to understand biological phenomena at a molecular level, and achieves this through the study of DNA, RNA, proteins, and/or other macromolecules (e.g., those involved in the modification of these substrates). Consequently, it relies on the availability of a wide variety of methods that deal with the collection, preservation, inactivation, separation, manipulation, imaging, and analysis of these molecules. As such the state of the art in the field of ebolavirus molecular biology research (and that of all other viruses) is largely intertwined with, if not driven by, advancements in the technical methodologies available for these kinds of studies. Here we review of the current state of our knowledge regarding ebolavirus biology and emphasize the associated methods that made these discoveries possible.

  9. Preparation of sumoylated substrates for biochemical analysis.

    PubMed

    Knipscheer, Puck; Klug, Helene; Sixma, Titia K; Pichler, Andrea

    2009-01-01

    Covalent modification of proteins with SUMO (small ubiquitin related modifier) affects many cellular processes like transcription, nuclear transport, DNA repair and cell cycle progression. Although hundreds of SUMO targets have been identified, for several of them the function remains obscure. In the majority of cases sumoylation is investigated via "loss of modification" analysis by mutating the relevant target lysine. However, in other cases this approach is not successful since mapping of the modification site is problematic or mutation does not cause an obvious phenotype. These latter cases ask for different approaches to investigate the target modification. One possibility is to choose the opposite approach, a "gain in modification" analysis by producing both SUMO modified and unmodified protein in vitro and comparing them in functional assays. Here, we describe the purification of the ubiquitin conjugating enzyme E2-25K, its in vitro sumoylation with recombinant enzymes and the subsequent separation and purification of the modified and the unmodified forms.

  10. 40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

  11. 40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

  12. 40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

  13. 40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

  14. 40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

  15. Knowledge, attitudes towards and acceptability of genetic modification in Germany.

    PubMed

    Christoph, Inken B; Bruhn, Maike; Roosen, Jutta

    2008-07-01

    Genetic modification remains a controversial issue. The aim of this study is to analyse the attitudes towards genetic modification, the knowledge about it and its acceptability in different application areas among German consumers. Results are based on a survey from spring 2005. An exploratory factor analysis is conducted to identify the attitudes towards genetic modification. The identified factors are used in a cluster analysis that identified a cluster of supporters, of opponents and a group of indifferent consumers. Respondents' knowledge of genetics and biotechnology differs among the found clusters without revealing a clear relationship between knowledge and support of genetic modification. The acceptability of genetic modification varies by application area and cluster, and genetically modified non-food products are more widely accepted than food products. The perception of personal health risks has high explanatory power for attitudes and acceptability.

  16. Using Agent Based Modeling (ABM) to Develop Cultural Interaction Simulations

    NASA Technical Reports Server (NTRS)

    Drucker, Nick; Jones, Phillip N.

    2012-01-01

    Today, most cultural training is based on or built around "cultural engagements" or discrete interactions between the individual learner and one or more cultural "others". Often, success in the engagement is the end or the objective. In reality, these interactions usually involve secondary and tertiary effects with potentially wide ranging consequences. The concern is that learning culture within a strict engagement context might lead to "checklist" cultural thinking that will not empower learners to understand the full consequence of their actions. We propose the use of agent based modeling (ABM) to collect, store, and, simulating the effects of social networks, promulgate engagement effects over time, distance, and consequence. The ABM development allows for rapid modification to re-create any number of population types, extending the applicability of the model to any requirement for social modeling.

  17. Positioning Europe for the EPITRANSCRIPTOMICS challenge.

    PubMed

    Jantsch, Michael F; Quattrone, Alessandro; O'Connell, Mary; Helm, Mark; Frye, Michaela; Macias-Gonzales, Manuel; Ohman, Marie; Ameres, Stefan; Willems, Luc; Fuks, Francois; Oulas, Anastasis; Vanacova, Stepanka; Nielsen, Henrik; Bousquet-Antonelli, Cecile; Motorin, Yuri; Roignant, Jean-Yves; Balatsos, Nikolaos; Dinnyes, Andras; Baranov, Pavel; Kelly, Vincent; Lamm, Ayelet; Rechavi, Gideon; Pelizzola, Mattia; Liepins, Janis; Holodnuka Kholodnyuk, Irina; Zammit, Vanessa; Ayers, Duncan; Drablos, Finn; Dahl, John Arne; Bujnicki, Janusz; Jeronimo, Carmen; Almeida, Raquel; Neagu, Monica; Costache, Marieta; Bankovic, Jasna; Banovic, Bojana; Kyselovic, Jan; Valor, Luis Miguel; Selbert, Stefan; Pir, Pinar; Demircan, Turan; Cowling, Victoria; Schäfer, Matthias; Rossmanith, Walter; Lafontaine, Denis; David, Alexandre; Carre, Clement; Lyko, Frank; Schaffrath, Raffael; Schwartz, Schraga; Verdel, Andre; Klungland, Arne; Purta, Elzbieta; Timotijevic, Gordana; Cardona, Fernando; Davalos, Alberto; Ballana, Ester; O Carroll, Donal; Ule, Jernej; Fray, Rupert

    2018-05-09

    The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.

  18. Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines

    PubMed Central

    Gibson, Gary E.; Xu, Hui; Chen, Huan-Lian; Chen, Wei; Denton, Travis; Zhang, Sheng

    2015-01-01

    Reversible post-translation modifications of proteins are common in all cells and appear to regulate many processes. Nevertheless, the enzyme(s) responsible for the alterations and the significance of the modification are largely unknown. Succinylation of proteins occurs and causes large changes in the structure of proteins; however, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins are unknown. These studies focused on succinylation of mitochondrial proteins. The results demonstrate that the α-ketoglutarate dehydrogenase complex (KGDHC) can serve as a trans-succinylase that mediates succinylation in an α-ketoglutarate-dependent manner. Inhibition of KGDHC reduced suc-cinylation of both cytosolic and mitochondrial proteins in cultured neurons and in a neuronal cell line. Purified KGDHC can succinylate multiple proteins including other enzymes of the tricarboxylic acid (TCA) cycle leading to modification of their activity. Inhibition of KGDHC also modifies acetylation by modifying the pyruvate dehydrogenase complex. The much greater effectiveness of KGDHC than succinyl CoA suggests that the catalysis due to the E2k suc-cinyltransferase is important. Succinylation appears to be a major signaling system and it can be mediated by KGDHC. PMID:25772995

  19. Changes in Structural-Mechanical Properties and Degradability of Collagen during Aging-associated Modifications*

    PubMed Central

    Panwar, Preety; Lamour, Guillaume; Mackenzie, Neil C. W.; Yang, Heejae; Ko, Frank; Li, Hongbin; Brömme, Dieter

    2015-01-01

    During aging, changes occur in the collagen network that contribute to various pathological phenotypes in the skeletal, vascular, and pulmonary systems. The aim of this study was to investigate the consequences of age-related modifications on the mechanical stability and in vitro proteolytic degradation of type I collagen. Analyzing mouse tail and bovine bone collagen, we found that collagen at both fibril and fiber levels varies in rigidity and Young's modulus due to different physiological changes, which correlate with changes in cathepsin K (CatK)-mediated degradation. A decreased susceptibility to CatK-mediated hydrolysis of fibrillar collagen was observed following mineralization and advanced glycation end product-associated modification. However, aging of bone increased CatK-mediated osteoclastic resorption by ∼27%, and negligible resorption was observed when osteoclasts were cultured on mineral-deficient bone. We observed significant differences in the excavations generated by osteoclasts and C-terminal telopeptide release during bone resorption under distinct conditions. Our data indicate that modification of collagen compromises its biomechanical integrity and affects CatK-mediated degradation both in bone and tissue, thus contributing to our understanding of extracellular matrix aging. PMID:26224630

  20. Genome editing and genetic engineering in livestock for advancing agricultural and biomedical applications.

    PubMed

    Telugu, Bhanu P; Park, Ki-Eun; Park, Chi-Hun

    2017-08-01

    Genetic modification of livestock has a longstanding and successful history, starting with domestication several thousand years ago. Modern animal breeding strategies predominantly based on marker-assisted and genomic selection, artificial insemination, and embryo transfer have led to significant improvement in the performance of domestic animals, and are the basis for regular supply of high quality animal derived food. However, the current strategy of breeding animals over multiple generations to introduce novel traits is not realistic in responding to the unprecedented challenges such as changing climate, pandemic diseases, and feeding an anticipated 3 billion increase in global population in the next three decades. Consequently, sophisticated genetic modifications that allow for seamless introgression of novel alleles or traits and introduction of precise modifications without affecting the overall genetic merit of the animal are required for addressing these pressing challenges. The requirement for precise modifications is especially important in the context of modeling human diseases for the development of therapeutic interventions. The animal science community envisions the genome editors as essential tools in addressing these critical priorities in agriculture and biomedicine, and for advancing livestock genetic engineering for agriculture, biomedical as well as "dual purpose" applications.

  1. Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.

    PubMed

    Vallejo, Daniela; Codocedo, Juan F; Inestrosa, Nibaldo C

    2017-04-01

    The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

  2. 76 FR 24349 - Airworthiness Directives; The Boeing Company Model 747-200B, -300, -400, -400D, and -400F Series...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ... consequent fracturing of the mid-pivot bolt assembly, which could lead to loss of the spring beam load path... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2010... No. 1 strut were inadvertently installed in the incorrect position during strut modification. We are...

  3. Improvements to the single screw extruder

    NASA Technical Reports Server (NTRS)

    Hiemenz, C.; Ziegmann, G.; Franzkoch, B.; Hoffmanns, W.; Michaeli, W.

    1977-01-01

    The extrusion on a single screw extruder is examined. The process is divided into several steps: the dosage of the materials to be conveyed; the modification of the shape of the feeding opening which influences the feeding process and consequently the throughput of the extruder; optimizing the shape of the feeding zone to meet the specific material requirements; and plasticizing and homogenizing.

  4. 75 FR 5055 - Taking and Importing Marine Mammals; U.S. Navy's Atlantic Fleet Active Sonar Training (AFAST)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ... U.S. to 45[deg] W. long. and south from the Atlantic and Gulf of Mexico Coasts to approximately 23..., hunt, capture, or kill or to attempt to harass, hunt, capture, or kill marine mammals. Regulations... modifications, all of which are of little to no consequence to marine mammals (in fact, the annual take...

  5. Controlling Flows Of Two Ingredients For Spraying

    NASA Technical Reports Server (NTRS)

    Chandler, Huel H.

    1995-01-01

    Closed-loop servo control subsystem incorporated, as modification, into system controlling flows of two ingredients mixed and sprayed to form thermally insulating foams on large tanks. Provides steady flows at specified rates. Foams produced smoother and of higher quality. Continued use of system results in substantial reduction in cost stemming from close control of application of foam and consequent reduced use of material.

  6. Obesogens and male fertility.

    PubMed

    Cardoso, A M; Alves, M G; Mathur, P P; Oliveira, P F; Cavaco, J E; Rato, L

    2017-01-01

    In the last decades, several studies evidenced a decrease in male fertility in developed countries. Although the aetiology of this trend in male reproductive health remains a matter of debate, environmental compounds that predispose to weight gain, namely obesogens, are appointed as contributors because of their action as endocrine disruptors. Obesogens favour adipogenesis by an imbalance of metabolic processes and can be found virtually everywhere. These compounds easily accumulate in tissues with high lipid content. Obesogens change the functioning of male reproductive axis, and, consequently, the testicular physiology and metabolism that are pivotal for spermatogenesis. The disruption of these tightly regulated metabolic pathways leads to adverse reproductive outcomes. Notably, adverse effects of obesogens may also promote disturbances in the metabolic performance of the following generations, through epigenetic modifications passed by male gametes. Thus, unveiling the molecular pathways by which obesogens induce toxicity that may end up in epigenetic modifications is imperative. Otherwise, a transgenerational susceptibility to metabolic diseases may be favoured. We present an up-to-date overview of the impact of obesogens on testicular physiology, with a particular focus on testicular metabolism. We also address the effects of obesogens on male reproductive parameters and the subsequent consequences for male fertility. © 2016 World Obesity Federation.

  7. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  8. Quantification of Lysine Acetylation and Succinylation Stoichiometry in Proteins Using Mass Spectrometric Data-Independent Acquisitions (SWATH)

    NASA Astrophysics Data System (ADS)

    Meyer, Jesse G.; D'Souza, Alexandria K.; Sorensen, Dylan J.; Rardin, Matthew J.; Wolfe, Alan J.; Gibson, Bradford W.; Schilling, Birgit

    2016-11-01

    Post-translational modification of lysine residues by NƐ-acylation is an important regulator of protein function. Many large-scale protein acylation studies have assessed relative changes of lysine acylation sites after antibody enrichment using mass spectrometry-based proteomics. Although relative acylation fold-changes are important, this does not reveal site occupancy, or stoichiometry, of individual modification sites, which is critical to understand functional consequences. Recently, methods for determining lysine acetylation stoichiometry have been proposed based on ratiometric analysis of endogenous levels to those introduced after quantitative per-acetylation of proteins using stable isotope-labeled acetic anhydride. However, in our hands, we find that these methods can overestimate acetylation stoichiometries because of signal interferences when endogenous levels of acylation are very low, which is especially problematic when using MS1 scans for quantification. In this study, we sought to improve the accuracy of determining acylation stoichiometry using data-independent acquisition (DIA). Specifically, we use SWATH acquisition to comprehensively collect both precursor and fragment ion intensity data. The use of fragment ions for stoichiometry quantification not only reduces interferences but also allows for determination of site-level stoichiometry from peptides with multiple lysine residues. We also demonstrate the novel extension of this method to measurements of succinylation stoichiometry using deuterium-labeled succinic anhydride. Proof of principle SWATH acquisition studies were first performed using bovine serum albumin for both acetylation and succinylation occupancy measurements, followed by the analysis of more complex samples of E. coli cell lysates. Although overall site occupancy was low (<1%), some proteins contained lysines with relatively high acetylation occupancy.

  9. Analysis of Protein Adduction Kinetics by Quantitative Mass Spectrometry. Competing Adduction Reactions of Glutathione-S-Transferase P1-1 with Electrophiles

    PubMed Central

    Orton, Christopher R.; Liebler, Daniel C.

    2007-01-01

    Defining the mechanisms and consequences of protein adduction is crucial to understanding the toxicity of reactive electrophiles. Application of tandem mass spectrometry and data analysis algorithms enables detection and mapping of chemical adducts at the level of amino acid sequence. Nevertheless, detection of adducts does not indicate relative reactivity of different sites. Here we describe a method to measure the kinetics of competing adduction reactions at different sites on the same protein. Adducts are formed by electrophiles at Cys14 and Cys47 on the metabolic enzyme glutathione-S-transferase P1-1 and modification is accompanied by a loss of enzymatic activity. Relative quantitation of protein adducts was done by tagging N-termini of peptide digests with isotopically labeled phenyl isocyanate and tracking the ratio of light-tagged peptide adducts to heavy-tagged reference samples in liquid chromatography-tandem mass spectrometry analyses using a multiple reaction monitoring method. This approach was used to measure rate constants for adduction at both positions with two different model electrophiles, N-iodoacetyl-N-biotinylhexylenediamine and 1-biotinamido-4-(4′-[maleimidoethyl-cyclohexane]-carboxamido)butane. The results indicate that Cys47 was approximately 2–3-fold more reactive toward both electrophiles than was Cys14. This result was consistent with the relative reactivity of these electrophiles in a complex proteome system and with previously reported trends in reactivity of these sites. Kinetic analyses of protein modification reactions provide a means of evaluating the selectivity of reactive mediators of chemical toxicity. PMID:17433278

  10. Highly Sensitive and High-Throughput Analysis of Plant Hormones Using MS-Probe Modification and Liquid Chromatography–Tandem Mass Spectrometry: An Application for Hormone Profiling in Oryza sativa

    PubMed Central

    Kojima, Mikiko; Kamada-Nobusada, Tomoe; Komatsu, Hirokazu; Takei, Kentaro; Kuroha, Takeshi; Mizutani, Masaharu; Ashikari, Motoyuki; Ueguchi-Tanaka, Miyako; Matsuoka, Makoto; Suzuki, Koji; Sakakibara, Hitoshi

    2009-01-01

    We have developed a highly sensitive and high-throughput method for the simultaneous analysis of 43 molecular species of cytokinins, auxins, ABA and gibberellins. This method consists of an automatic liquid handling system for solid phase extraction and ultra-performance liquid chromatography (UPLC) coupled with a tandem quadrupole mass spectrometer (qMS/MS) equipped with an electrospray interface (ESI; UPLC-ESI-qMS/MS). In order to improve the detection limit of negatively charged compounds, such as gibberellins, we chemically derivatized fractions containing auxin, ABA and gibberellins with bromocholine that has a quaternary ammonium functional group. This modification, that we call ‘MS-probe’, makes these hormone derivatives have a positive ion charge and permits all compounds to be measured in the positive ion mode with UPLC-ESI-qMS/MS in a single run. Consequently, quantification limits of gibberellins increased up to 50-fold. Our current method needs <100 mg (FW) of plant tissues to determine phytohormone profiles and enables us to analyze >180 plant samples simultaneously. Application of this method to plant hormone profiling enabled us to draw organ distribution maps of hormone species in rice and also to identify interactions among the four major hormones in the rice gibberellin signaling mutants, gid1-3, gid2-1 and slr1. Combining the results of hormone profiling data with transcriptome data in the gibberellin signaling mutants allows us to analyze relationships between changes in gene expression and hormone metabolism. PMID:19369275

  11. The effects of low-temperature plasma treatment on the capillary properties of inorganic fibers

    NASA Astrophysics Data System (ADS)

    Garifullin, A. R.; Abdullin, I. Sh; Skidchenko, E. A.; Krasina, I. V.; Shaekhov, M. F.

    2016-01-01

    Solving the problem of achieving high adhesion between the components in the polymeric composite material (PCM) based on carbon fibers (CF) and basalt fibers (BF) is proposed to use the radio-frequency (RF) plasma under lower pressure by virtue of efficiency, environmental friendliness and rationality of the method. The paper gives the results of studies of the properties of CF and BF after RF capacitive discharge plasma treatment. The plasma modification modes of carbon and basalt fiber were investigated. The efficiency of treatment tool in surface properties modification of carbon and basalt fibers was found, namely capillary properties of CF and BF were researched. The optimal treatment modes were selected. It was found that the method of plasma modification in the radio-frequency capacitive discharge under the lower pressure contributes enhancing the capillary properties of inorganic fibers, in particular carbon and basalt ones. It shows the tendency to increase of the adhesive properties in PCM, and, consequently, the increase of the physical and mechanical properties of the products.

  12. Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.

    PubMed

    Parvez, Saba; Fu, Yuan; Li, Jiayang; Long, Marcus J C; Lin, Hong-Yu; Lee, Dustin K; Hu, Gene S; Aye, Yimon

    2015-01-14

    Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology.

  13. Effects of Computer-Based Training on Procedural Modifications to Standard Functional Analyses

    ERIC Educational Resources Information Center

    Schnell, Lauren K.; Sidener, Tina M.; DeBar, Ruth M.; Vladescu, Jason C.; Kahng, SungWoo

    2018-01-01

    Few studies have evaluated methods for training decision-making when functional analysis data are undifferentiated. The current study evaluated computer-based training to teach 20 graduate students to arrange functional analysis conditions, analyze functional analysis data, and implement procedural modifications. Participants were exposed to…

  14. Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

    PubMed

    Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

    2017-10-04

    Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

  15. Substitution of modified starch with hydrogen peroxide-modified rice bran in salad dressing formulation: physicochemical, texture, rheological and sensory properties.

    PubMed

    Maani, Bahareh; Alimi, Mazdak; Shokoohi, Shirin; Fazeli, Fatemeh

    2017-06-01

    Rice bran samples were treated under different conditions including hydrogen peroxide content (1, 4, and 7 wt%) and media pH (10.5, 11.5, and 12.5). Water holding capacity and color measurement results showed acceptable improvements compared with the untreated native bran confirmed by Fourier transform infrared analysis. Optimization of modification conditions upon characterization results suggested the introduction of 7% hydrogen peroxide at pH = 12.5. Accordingly, 1, 2 and 3 wt% of the rice bran treated under the optimized conditions, was used in salad dressing formulation; as for .3 wt% of modified starch in the formulation of blank sample, 1 wt% of treated rice bran dietary fiber was substituted. Biopolymer swelling and formation of a stable viscous gel network promoted by the chemical treatment of lignocellulosic rice bran restrict the mobility of oil droplets dispersed in the continuous phase which would consequently retard the emulsion instability phenomena. This effect was also confirmed by flow behavior and viscoelastic characterization results. Salad dressing samples containing 1 and 2 wt% treated rice bran showed acceptable physicochemical, rheological and organoleptic properties besides superior nutritional characteristics compared with the commercial modified starch traditionally used in salad dressing formulations. Despite recommended consumption of dietary fibers, addition of unprocessed lignocellulosic materials to food products usually raise negative effects in sensory, color, and texture quality. This study investigates the modification of rice bran, the byproduct of brown rice milling, to substitute modified starch traditionally used in salad dressing formulations to achieve optimum properties desirable for the final product. Optimization of modification conditions upon characterization of the formulated samples in this study would suggest new improved formulation for the commercial product. © 2016 Wiley Periodicals, Inc.

  16. Nanoparticles for Protein Sensing in Primary Containers: Interaction Analysis and Application.

    PubMed

    Pérez Medina Martínez, Víctor; Espinosa-de la Garza, Carlos E; Méndez-Silva, Diego A; Bolívar-Vichido, Mariana; Flores-Ortiz, Luis F; Pérez, Néstor O

    2018-05-01

    Silver nanoparticles (AgNPs) are known to interact with proteins, leading to modifications of the plasmonic absorption that can be used to monitor this interaction, entailing a promising application for sensing adsorption of therapeutic proteins in primary containers. First, transmission electron microscopy in combination with plasmonic absorption and light scattering responses were used to characterize AgNPs and protein-AgNP complexes, including its concentration dependence, using two therapeutic molecules as models: a monoclonal antibody (mAb) and a synthetic copolymer (SC). Upon interaction, a protein corona was formed around AgNPs with the consequent shifting and broadening of their characteristic surface plasmon resonance (SPR) band (400 nm) to 410 nm and longer wavelenghts. Additional studies revealed secondary and three-dimensional structure modifications of model proteins upon interaction with AgNPs by circular dichroism and fluorescence techniques, respectively. Based on the modification of the SPR condition of AgNPs upon interaction with proteins, we developed a novel protein-sensing application of AgNPs in primary containers. This strategy was used to conduct a compatibility assessment of model proteins towards five commercially available prefillable glass syringe (PFS) models. mAb- and SC-exposed PFSs showed that 74 and 94% of cases were positive for protein adsorption, respectively. Interestingly, protein adsorption on 15% of total tested PFSs was negligible (below the nanogram level). Our results highlight the need of a case-by-case compatibility assessment of therapeutic proteins and their primary containers. This strategy has the potential to be easily applied on other containers and implemented during early-stage product development by pharmaceutical companies and for routine use during batch release by packaging manufacturers.

  17. Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1.

    PubMed

    Hager, Marlies V; Clydesdale, Lachlan; Gellman, Samuel H; Sexton, Patrick M; Wootten, Denise

    2017-07-15

    The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor that is a major therapeutic target for the treatment of type 2 diabetes. Activation of this receptor promotes insulin secretion and blood glucose regulation. The GLP-1R can initiate signaling through several intracellular pathways upon activation by GLP-1. GLP-1R ligands that preferentially stimulate subsets among the natural signaling pathways ("biased agonists") could be useful as tools for elucidating the consequences of specific pathways and might engender therapeutic agents with tailored effects. Using HEK-293 cells recombinantly expressing human GLP-1R, we have previously reported that backbone modification of GLP-1, via replacement of selected α-amino acid residues with β-amino acid residues, generates GLP-1 analogues with distinctive preferences for promoting G protein activation versus β-arrestin recruitment. Here, we have explored the influence of cell background across these two parameters and expanded our analysis to include affinity and other key signaling pathways (intracellular calcium mobilization and ERK phosphorylation) using recombinant human GLP-1R expressed in a CHO cell background, which has been used extensively to demonstrate biased agonism of GLP-1R ligands. The new data indicate that α/β-peptide analogues of GLP-1 exhibit a range of distinct bias profiles relative to GLP-1 and that broad assessment of signaling endpoints is required to reveal the spectrum of behavior of modified peptides. These results support the view that backbone modification via α→β amino acid replacement can enable rapid discovery of peptide hormone analogues that display substantial signal bias at a cognate GPCR. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy

    PubMed Central

    Devaux, Marie-Françoise; Jamme, Frédéric; André, William; Bouchet, Brigitte; Alvarado, Camille; Durand, Sylvie; Robert, Paul; Saulnier, Luc; Bonnin, Estelle; Guillon, Fabienne

    2018-01-01

    Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation. Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved. In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls. Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction. Image analysis was used to quantify the fluorescence intensity variations. Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls. Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation. Hemicellulose degradation was found to occur prior to cellulose degradation using a Celluclast® preparation. Combining the fluorescence and FT-IR information yielded the conclusion that enzymes did not bind to lignified cell walls, which were consequently not degraded. Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell. Fluorescence intensity quantification showed that the enzymes were not evenly distributed, and their amount increased progressively on degradable cell walls. During degradation, adjacent cells were separated and the cell wall fragmented until complete degradation. PMID:29515611

  19. Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells.

    PubMed

    Kitchen, Mark O; Yacqub-Usman, Kiren; Emes, Richard D; Richardson, Alan; Clayton, Richard N; Farrell, William E

    2015-10-01

    Transgenic mice overexpressing the high mobility group A (HMGA) genes, Hmga1 or Hmga2 develop pituitary tumours and their overexpression is also a frequent finding in human pituitary adenomas. In some cases, increased expression of HMGA2 but not that of HMGA1 is consequent to genetic perturbations. However, recent studies show that down-regulation of microRNA (miRNA), that contemporaneously target the HMGA1 and HMGA2 transcripts, are associated with their overexpression. In a cohort of primary pituitary adenoma we determine the impact of epigenetic modifications on the expression of HMGA-targeting miRNA. For these miRNAs, chromatin immunoprecipitations showed that transcript down-regulation is correlated with histone tail modifications associated with condensed silenced genes. The functional impact of epigenetic modification on miRNA expression was determined in the rodent pituitary cell line, GH3. In these cells, histone tail, miRNA-associated, modifications were similar to those apparent in human adenoma and likely account for their repression. Indeed, challenge of GH3 cells with the epidrugs, zebularine and TSA, led to enrichment of the histone modification, H3K9Ac, associated with active genes, and depletion of the modification, H3K27me3, associated with silent genes and re-expression of HMGA-targeting miRNA. Moreover, epidrugs challenges were also associated with a concomitant decrease in hmga1 transcript and protein levels and concurrent increase in bmp-4 expression. These findings show that the inverse relationship between HMGA expression and targeting miRNA is reversible through epidrug interventions. In addition to showing a mechanistic link between epigenetic modifications and miRNA expression these findings underscore their potential as therapeutic targets in this and other diseases.

  20. Global translational impacts of the loss of the tRNA modification t6A in yeast.

    PubMed

    Thiaville, Patrick C; Legendre, Rachel; Rojas-Benítez, Diego; Baudin-Baillieu, Agnès; Hatin, Isabelle; Chalancon, Guilhem; Glavic, Alvaro; Namy, Olivier; de Crécy-Lagard, Valérie

    2016-01-01

    The universal tRNA modification t 6 A is found at position 37 of nearly all tRNAs decoding ANN codons. The absence of t 6 A 37 leads to severe growth defects in baker's yeast, phenotypes similar to those caused by defects in mcm 5 s 2 U 34 synthesis. Mutants in mcm 5 s 2 U 34 can be suppressed by overexpression of tRNA Lys UUU , but we show t 6 A phenotypes could not be suppressed by expressing any individual ANN decoding tRNA, and t 6 A and mcm 5 s 2 U are not determinants for each other's formation. Our results suggest that t 6 A deficiency, like mcm 5 s 2 U deficiency, leads to protein folding defects, and show that the absence of t 6 A led to stress sensitivities (heat, ethanol, salt) and sensitivity to TOR pathway inhibitors. Additionally, L-homoserine suppressed the slow growth phenotype seen in t 6 A-deficient strains, and proteins aggregates and Advanced Glycation End-products (AGEs) were increased in the mutants. The global consequences on translation caused by t 6 A absence were examined by ribosome profiling. Interestingly, the absence of t 6 A did not lead to global translation defects, but did increase translation initiation at upstream non-AUG codons and increased frame-shifting in specific genes. Analysis of codon occupancy rates suggests that one of the major roles of t 6 A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I 34 :C 3 pairs while increasing the elongation rate of rare tRNAs and G 34 :U 3 pairs. This work reveals that the consequences of t 6 A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes.

  1. Maillard reaction versus other nonenzymatic modifications in neurodegenerative processes.

    PubMed

    Pamplona, Reinald; Ilieva, Ekaterina; Ayala, Victoria; Bellmunt, Maria Josep; Cacabelos, Daniel; Dalfo, Esther; Ferrer, Isidre; Portero-Otin, Manuel

    2008-04-01

    Nonenzymatic protein modifications are generated from direct oxidation of amino acid side chains and from reaction of the nucleophilic side chains of specific amino acids with reactive carbonyl species. These reactions give rise to specific markers that have been analyzed in different neurodegenerative diseases sharing protein aggregation, such as Alzheimer's disease, Pick's disease, Parkinson's disease, dementia with Lewy bodies, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis. Collectively, available data demonstrate that oxidative stress homeostasis, mitochondrial function, and energy metabolism are key factors in determining the disease-specific pattern of protein molecular damage. In addition, these findings suggest the lack of a "gold marker of oxidative stress," and, consequently, they strengthen the need for a molecular dissection of the nonenzymatic reactions underlying neurodegenerative processes.

  2. Description, validation, and modification of the Guyton model for space-flight applications. Part A. Guyton model of circulatory, fluid and electrolyte control. Part B. Modification of the Guyton model for circulatory, fluid and electrolyte control

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1985-01-01

    The mathematical model that has been a cornerstone for the systems analysis of space-flight physiological studies is the Guyton model describing circulatory, fluid and electrolyte regulation. The model and the modifications that are made to permit simulation and analysis of the stress of weightlessness are described.

  3. Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.

    PubMed

    Wagner, Monika; Khoury, Hanane; Willet, Jacob; Rindress, Donna; Goetghebeur, Mireille

    2016-03-01

    The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. The adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions.

  4. Land use change in the last century in the Veneto floodplain: effects on network drainage density, water storage, and related consequences on flood risk

    NASA Astrophysics Data System (ADS)

    Prosdocimi, Massimo; Sofia, Giulia; Dalla Fontana, Giancarlo; Tarolli, Paolo

    2013-04-01

    In a high-density populated country such as Italy, the anthropic pressure plays a fundamental role in the alteration and the modification of the landscape. Among the most evident anthropic alterations, the most important are the urbanization processes that have been occurring since the end of the second world war. Agricultural activities, housing and other land uses have shifted due to the progressive spreading of urban areas. These modifications affect the hydrologic regimes, but municipalities often are not aware of the real impact of land cover changes on such processes and, consequently, an increase of the elements at risk of flooding is generally registered. The main objective of this work is to evaluate the impact of land cover changes in the Veneto region (north-east Italy), from 1954 to 2006, on the minor drainage network system and on its capacity to attenuate the direct runoff. The major flood event occurred between October and November 2010. The study is a typical agrarian landscape and it has been chosen considering its involvement inthe major flood of 2010 and considering also the availability of high-resolution topographic data (LiDAR-derived DTMs) and historical aerial photographs. Aerial photographs dated back to 1954 and 1981, in particular, have been used either to classify the land cover in five categories according to the first level of the CORINE land cover classification and to identify the minor drainage network. A semi-automatic approach based on the high-resolution DTM (Cazorzi et al., 2012), was also considered to identify the minor drainage network and estimate its water storage capacity. The results underline how land cover variation over the last 50 years has strongly increased the propension of the soil to produce direct runoff (increase of the Curve Number value) and it has also reduced the extent of the minor network system. As a consequence, the capacity of the agrarian minor network to attenuate and laminate a flood event is decreased as well. These analysis can be considered useful tools for a suitable land use planning in flood prone areas. References Cazorzi, F., Dalla Fontana, G., De Luca, A., Sofia, G., Tarolli, P. (2012). Drainage network detection and assessment of network storage capacity in agrarian landscape, Hydrological Processes, ISSN: 0885-6087, doi:10.1002/hyp.9224

  5. 40 CFR 1400.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION... analysis (OCA) information means sections 2 through 5 of a risk management plan (consisting of an... consequence analysis (OCA) data elements means the results of the off-site consequence analysis conducted by a...

  6. 40 CFR 1400.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION... analysis (OCA) information means sections 2 through 5 of a risk management plan (consisting of an... consequence analysis (OCA) data elements means the results of the off-site consequence analysis conducted by a...

  7. 40 CFR 1400.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION... analysis (OCA) information means sections 2 through 5 of a risk management plan (consisting of an... consequence analysis (OCA) data elements means the results of the off-site consequence analysis conducted by a...

  8. 40 CFR 1400.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION... analysis (OCA) information means sections 2 through 5 of a risk management plan (consisting of an... consequence analysis (OCA) data elements means the results of the off-site consequence analysis conducted by a...

  9. Structural and energetic consequences of mutations in a solvated hydrophobic cavity

    NASA Technical Reports Server (NTRS)

    Adamek, D. H.; Guerrero, L.; Blaber, M.; Caspar, D. L. D.

    2005-01-01

    The structural and energetic consequences of modifications to the hydrophobic cavity of interleukin 1-beta (IL-1beta) are described. Previous reports demonstrated that the entirely hydrophobic cavity of IL-1beta contains positionally disordered water. To gain a better understanding of the nature of this cavity and the water therein, a number of mutant proteins were constructed by site-directed mutagenesis, designed to result in altered hydrophobicity of the cavity. These mutations involve the replacement of specific phenylalanine residues, which circumscribe the cavity, with tyrosine, tryptophan, leucine and isoleucine. Using differential scanning calorimetry to determine the relative stabilities of the wild-type and mutant proteins, we found all of the mutants to be destabilizing. X-ray crystallography was used to identify the structural consequences of the mutations. No clear correlation between the hydrophobicities of the specific side-chains introduced and the resulting stabilities was found.

  10. An Analysis of Modifications to the Three-Step Guided Compliance Procedure Necessary to Achieve Compliance among Preschool Children

    ERIC Educational Resources Information Center

    Wilder, David A.; Myers, Kristin; Fischetti, Anthony; Leon, Yanerys; Nicholson, Katie; Allison, Janelle

    2012-01-01

    After a 3-step guided compliance procedure (vocal prompt, vocal plus model prompt, vocal prompt plus physical guidance) did not increase compliance, we evaluated 2 modifications with 4 preschool children who exhibited noncompliance. The first modification consisted of omission of the model prompt, and the second modification consisted of omitting…

  11. Reactivity effects of moderator voids

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

    Ahlfeld, C.E.; Pryor, R.J.

    1975-01-01

    Reactivity worths for large moderator voids similar to those produced by steaming in postulated reactor transients were measured in the Process Development Pile (PDP) reactor. The experimental results were compared to the computed void worths obtained from techniques currently used in routine safety analyses. Neutron energy spectrum measurements were used to verify a modified lattice pattern that correctly computed the measured spectrum, and consequently, improved macroscopic cross sections. In addition, a special two-dimensional transport calculation was performed to obtain an axially defined diffusion coefficient for the void region. The combination of the modified lattice calculations and the axial diffusion coefficientmore » yielded void reactivity worths which agreed very well with experiment. It was concluded that the computational modules available in the JOSHUA system (GLASS, GRIMHX) would yield accurate void reactivity worths in SLR--SRP safety analysis studies, provided the above mentioned modifications were made.« less

  12. Global profiling of lysine reactivity and ligandability in the human proteome

    NASA Astrophysics Data System (ADS)

    Hacker, Stephan M.; Backus, Keriann M.; Lazear, Michael R.; Forli, Stefano; Correia, Bruno E.; Cravatt, Benjamin F.

    2017-12-01

    Nucleophilic amino acids make important contributions to protein function, including performing key roles in catalysis and serving as sites for post-translational modification. Electrophilic groups that target amino-acid nucleophiles have been used to create covalent ligands and drugs, but have, so far, been mainly limited to cysteine and serine. Here, we report a chemical proteomic platform for the global and quantitative analysis of lysine residues in native biological systems. We have quantified, in total, more than 9,000 lysines in human cell proteomes and have identified several hundred residues with heightened reactivity that are enriched at protein functional sites and can frequently be targeted by electrophilic small molecules. We have also discovered lysine-reactive fragment electrophiles that inhibit enzymes by active site and allosteric mechanisms, as well as disrupt protein-protein interactions in transcriptional regulatory complexes, emphasizing the broad potential and diverse functional consequences of liganding lysine residues throughout the human proteome.

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

    Bettoni, Dario; Nusser, Adi; Blas, Diego

    We develop the framework for testing Lorentz invariance in the dark matter sector using galactic dynamics. We consider a Lorentz violating (LV) vector field acting on the dark matter component of a satellite galaxy orbiting in a host halo. We introduce a numerical model for the dynamics of satellites in a galactic halo and for a galaxy in a rich cluster to explore observational consequences of such an LV field. The orbital motion of a satellite excites a time dependent LV force which greatly affects its internal dynamics. Our analysis points out key observational signatures which serve as probes ofmore » LV forces. These include modifications to the line of sight velocity dispersion, mass profiles and shapes of satellites. With future data and a more detailed modeling these signatures can be exploited to constrain a new region of the parameter space describing the LV in the dark matter sector.« less

  14. Effect of Thymine Starvation on Messenger Ribonucleic Acid Synthesis in Escherichia coli

    PubMed Central

    Luzzati, Denise

    1966-01-01

    Luzzati, Denise (Institut de Biologie Physico-Chimique, Paris, France). Effect of thymine starvation on messenger ribonucleic acid synthesis in Escherichia coli. J. Bacteriol. 92:1435–1446. 1966.—During the course of thymine starvation, the rate of synthesis of messenger ribonucleic acid (mRNA, the rapidly labeled fraction of the RNA which decays in the presence of dinitrophenol or which hybridizes with deoxyribonucleic acid) decreases exponentially, in parallel with the viability of the thymine-starved bacteria. The ability of cell-free extracts of starved bacteria to incorporate ribonucleoside triphosphates into RNA was determined; it was found to be inferior to that of extracts from control cells. The analysis of the properties of cell-free extracts of starved cells shows that their decreased RNA polymerase activity is the consequence of a modification of their deoxyribonucleic acid, the ability of which to serve as a template for RNA polymerase decreases during starvation. PMID:5332402

  15. Fractal Analysis of Rock Joint Profiles

    NASA Astrophysics Data System (ADS)

    Audy, Ondřej; Ficker, Tomáš

    2017-10-01

    Surface reliefs of rock joints are analyzed in geotechnics when shear strength of rocky slopes is estimated. The rock joint profiles actually are self-affine fractal curves and computations of their fractal dimensions require special methods. Many papers devoted to the fractal properties of these profiles were published in the past but only a few of those papers employed a convenient computational method that would have guaranteed a sound value of that dimension. As a consequence, anomalously low dimensions were presented. This contribution deals with two computational modifications that lead to sound fractal dimensions of the self-affine rock joint profiles. These are the modified box-counting method and the modified yard-stick method sometimes called the compass method. Both these methods are frequently applied to self-similar fractal curves but the self-affine profile curves due to their self-affine nature require modified computational procedures implemented in computer programs.

  16. Entropy Constraints in the Ground State Formation of Magnetically Frustrated Systems

    NASA Astrophysics Data System (ADS)

    Sereni, Julian G.

    2018-01-01

    A systematic modification of the entropy trajectory (S_m(T)) is observed at very low temperature in magnetically frustrated systems as a consequence of the constraint (S_mg 0) imposed by the Nernst postulate. The lack of magnetic order allows to explore and compare new thermodynamic properties by tracing the specific heat (C_m) behavior down to the sub-Kelvin range. Some of the most relevant findings are: (i) a common C_m/T|_{T→ 0} ≈ 7 J/mol K^2 `plateau' in at least five Yb-based very-heavy-fermions (VHF) compounds; (ii) quantitative and qualitative differences between VHF and standard non-Fermi-liquids; (iii) entropy bottlenecks governing the change of S_m(T) trajectories in a continuous transition into alternative ground states. A comparative analysis of S_m(T→ 0) dependencies is performed in compounds suitable for adiabatic demagnetization processes according to their partial ^2 S_m/partial T^2 derivatives.

  17. Whole genome DNA methylation: beyond genes silencing.

    PubMed

    Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

    2017-01-17

    The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the major biological consequences of DNA methylation recently discovered. We also discuss the necessity of tuning DNA methylation resolution into an adequate scale to ease the integration of the methylome information with other chromatin features and transcription events such as gene expression, nucleosome positioning, transcription factors binding dynamic, gene splicing and genomic imprinting. Finally, our review sheds light on DNA methylation heterogeneity in cell population and the different approaches used for its assessment, including the contribution of single cell DNA analysis technology.

  18. Whole genome DNA methylation: beyond genes silencing

    PubMed Central

    Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

    2017-01-01

    The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the major biological consequences of DNA methylation recently discovered. We also discuss the necessity of tuning DNA methylation resolution into an adequate scale to ease the integration of the methylome information with other chromatin features and transcription events such as gene expression, nucleosome positioning, transcription factors binding dynamic, gene splicing and genomic imprinting. Finally, our review sheds light on DNA methylation heterogeneity in cell population and the different approaches used for its assessment, including the contribution of single cell DNA analysis technology. PMID:27895318

  19. The etiology of low back pain in military helicopter aviators: prevention and treatment.

    PubMed

    Pelham, Thomas W; White, Harold; Holt, Laurence E; Lee, S Wayne

    2005-01-01

    Low back pain (LPB) is a major health problem among military rotary-wing aircrews worldwide. In order to define the etiology and propose remedies to LBP in helicopter aviators a review and critique of the literature was conducted. In-flight sitting posture and vibration generated by the aircraft were identified as high risk factors for LBP. Consequently, researchers recommended ergonomic modifications to the crew stations. The efficacy of these technical interventions has not been proven. As well, these design changes are not financially practical. Following an in depth kinesiological analysis of the physical demands of this type of flying, and preliminary experimentation, an alternative aeromedical approach focusing on the aircrew rather than the craft is presented. The authors propose a set of flight-specific exercises that might effectively deal with this problem. A thorough testing of this approach is envisioned.

  20. Global profiling of lysine reactivity and ligandability in the human proteome.

    PubMed

    Hacker, Stephan M; Backus, Keriann M; Lazear, Michael R; Forli, Stefano; Correia, Bruno E; Cravatt, Benjamin F

    2017-12-01

    Nucleophilic amino acids make important contributions to protein function, including performing key roles in catalysis and serving as sites for post-translational modification. Electrophilic groups that target amino-acid nucleophiles have been used to create covalent ligands and drugs, but have, so far, been mainly limited to cysteine and serine. Here, we report a chemical proteomic platform for the global and quantitative analysis of lysine residues in native biological systems. We have quantified, in total, more than 9,000 lysines in human cell proteomes and have identified several hundred residues with heightened reactivity that are enriched at protein functional sites and can frequently be targeted by electrophilic small molecules. We have also discovered lysine-reactive fragment electrophiles that inhibit enzymes by active site and allosteric mechanisms, as well as disrupt protein-protein interactions in transcriptional regulatory complexes, emphasizing the broad potential and diverse functional consequences of liganding lysine residues throughout the human proteome.

  1. Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation

    PubMed Central

    Blaze, Jennifer; Roth, Tania L.

    2015-01-01

    While it is well-known that stress during development and adulthood can confer long-term neurobiological and behavioral consequences, investigators have only recently begun to assess epigenetic modifications associated with these consequences. In this review, we highlight clinical research and work with animal models that provide evidence of the impact of stressful experiences either during the perinatal period or adulthood on DNA methylation and behavior. Additionally, we explore the more controversial concept of transgenerational inheritance, including that associated with preconception stress experienced by the mother or father. Finally, we discuss challenges associated with the idea of transgenerational epigenetics and for the field of epigenetics in general. PMID:25917771

  2. Manipulating Cells with Static Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Valles, J. M.; Guevorkian, K.

    2005-07-01

    We review our investigations of the use of static magnetic fields, B, for manipulating cells and cellular processes. We describe how B fields modify the cell division pattern of frog embryos and consequently can be used to probe the pattern determinants. We also observe that magnetic fields modify the swimming behavior of Paramecium Caudatum. We describe these modifications and their potential application to investigations of their swimming behavior.

  3. [Neuropsychological changes in schizophrenia and its modification].

    PubMed

    Penadés, R; Boget, T; Salamero, M; Catarineu, S; Bernardo, M

    2000-12-01

    The main experimental works about neuropsychological impairments of schizophrenia are reviewed. The underlying mechanisms of the cognitive deficits are set in a framework of the limited capacity model. In second point, the current status of the modificability of the cognitive deficits and the clinical and psychosocial consequences of this deficits are presented. At least, neuropsychological rehabilitation programs are reviewed from a clinical point of view.

  4. 40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

  5. 40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

  6. 40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

  7. 40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

  8. Loss of conformational stability in calmodulin upon methionine oxidation.

    PubMed Central

    Gao, J; Yin, D H; Yao, Y; Sun, H; Qin, Z; Schöneich, C; Williams, T D; Squier, T C

    1998-01-01

    We have used electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and fluorescence spectroscopy to investigate the secondary and tertiary structural consequences that result from oxidative modification of methionine residues in wheat germ calmodulin (CaM), and prevent activation of the plasma membrane Ca-ATPase. Using ESI-MS, we have measured rates of modification and molecular mass distributions of oxidatively modified CaM species (CaMox) resulting from exposure to H2O2. From these rates, we find that oxidative modification of methionine to the corresponding methionine sulfoxide does not predispose CaM to further oxidative modification. These results indicate that methionine oxidation results in no large-scale alterations in the tertiary structure of CaMox, because the rates of oxidative modification of individual methionines are directly related to their solvent exposure. Likewise, CD measurements indicate that methionine oxidation results in little change in the apparent alpha-helical content at 28 degrees C, and only a small (0.3 +/- 0.1 kcal mol(-1)) decrease in thermal stability, suggesting the disruption of a limited number of specific noncovalent interactions. Fluorescence lifetime, anisotropy, and quenching measurements of N-(1-pyrenyl)-maleimide (PMal) covalently bound to Cys26 indicate local structural changes around PMal in the amino-terminal domain in response to oxidative modification of methionine residues in the carboxyl-terminal domain. Because the opposing globular domains remain spatially distant in both native and oxidatively modified CaM, the oxidative modification of methionines in the carboxyl-terminal domain are suggested to modify the conformation of the amino-terminal domain through alterations in the structural features involving the interdomain central helix. The structural basis for the linkage between oxidative modification and these global conformational changes is discussed in terms of possible alterations in specific noncovalent interactions that have previously been suggested to stabilize the central helix in CaM. PMID:9512014

  9. Development of a Process Signature for Manufacturing Processes with Thermal Loads

    NASA Astrophysics Data System (ADS)

    Frerichs, Friedhelm; Meyer, Heiner; Strunk, Rebecca; Kolkwitz, Benjamin; Epp, Jeremy

    2018-06-01

    The newly proposed concept of Process Signatures enables the comparison of seemingly different manufacturing processes via a process-independent approach based on the analysis of the loading condition and resulting material modification. This contribution compares the recently published results, based on numerically achieved data for the development of Process Signatures for sole surface and volume heatings without phase transformations, with the experimental data. The numerical approach applies the moving heat source theory in combination with energetic quantities. The external thermal loadings of both processes were characterized by the resulting temperature development, which correlates with a change in the residual stress state. The numerical investigations show that surface and volume heatings are interchangeable for certain parameter regimes regarding the changes in the residual stress state. Mainly, temperature gradients and thermal diffusion are responsible for the considered modifications. The applied surface- and volume-heating models are used in shallow cut grinding and induction heating, respectively. The comparison of numerical and experimental data reveals similarities, but also some systematic deviations of the residual stresses at the surface. The evaluation and final discussion support the assertion for very fast stress relaxation processes within the subsurface region. A consequence would be that the stress relaxation processes, which are not yet included in the numerical models, must be included in the Process Signatures for sole thermal impacts.

  10. A Performance Comparison for Two Versions of the Vulcan Photometer

    NASA Technical Reports Server (NTRS)

    Borucki, W. J.; Caldwell, D. A.; Koch, D. G.; Jenkins, J. M.; Showen, R. L.

    2001-01-01

    Analysis of the images produced by the first version (V1) of the Vulcan photometer indicated that two major sources of noise were sky brightness and image motion. To reduce the effect of the sky brightness, a second version (V2) with a longer focal length and a larger format detector was developed and tested. The first version consisted of 15-centimeter (cm) focal length, F/1.5 Aerojet Delft reconnaissance lens, and a 2048 x 2048 format front-illuminated charged coupled device (CCD) with 9 microns micropixels (Mpixels). The second version used a 30-cm focal length, F/2.5 Kodak AeroEktar lens, and a 4096 x 4096 format CCD with 9 micro pixels. Both have a 49-square-degree field of view (FOV) but the area of the sky subtended by each pixel in the V2 version is one-fourth that of the V1 version. This modification substantially reduces the shot noise due to the sky background and allows fainter stars to be monitored for planetary transits. To remove the data gap and consequent signal-level change caused by flipping the photometer around the declination axis and to reduce image movement on the detector, several other modifications were incorporated. These include modifying the mount and stiffening the photometer and autoguider structures to reduce flexure. This paper compares the performance characteristics of each photometer and discusses tests to identify sources of systematic noise.

  11. Proteome analysis of Acetobacter pasteurianus during acetic acid fermentation.

    PubMed

    Andrés-Barrao, Cristina; Saad, Maged M; Chappuis, Marie-Louise; Boffa, Mauro; Perret, Xavier; Ortega Pérez, Ruben; Barja, François

    2012-03-16

    Acetic acid bacteria (AAB) are Gram-negative, strictly aerobic microorganisms that show a unique resistance to ethanol (EtOH) and acetic acid (AcH). Members of the Acetobacter and Gluconacetobacter genera are capable of transforming EtOH into AcH via the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes and are used for the industrial production of vinegar. Several mechanisms have been proposed to explain how AAB resist high concentrations of AcH, such as the assimilation of acetate through the tricarboxylic acid (TCA) cycle, the export of acetate by various transporters and modifications of the outer membrane. However, except for a few acetate-specific proteins, little is known about the global proteome responses to AcH. In this study, we used 2D-DIGE to compare the proteome of Acetobacter pasteurianus LMG 1262(T) when growing in glucose or ethanol and in the presence of acetic acid. Interesting protein spots were selected using the ANOVA p-value of 0.05 as threshold and 1.5-fold as the minimal level of differential expression, and a total of 53 proteins were successfully identified. Additionally, the size of AAB was reduced by approximately 30% in length as a consequence of the acidity. A modification in the membrane polysaccharides was also revealed by PATAg specific staining. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Influence of tooth profile on the noncircular gear tooth contact

    NASA Astrophysics Data System (ADS)

    Cristescu, A.; Andrei, L.; Cristescu, B.

    2017-02-01

    With noncircular gears, the continuous modification of the tooth meshing, in terms of variation of the tooth profiles and the line of action position and inclination, makes difficult the implementation of a general standard procedure for the analysis of the noncircular gears tooth contact. In this paper, the authors present a graphical approach that enables the tooth contact static pattern to be produced and evaluated in case of a noncircular gear with complex geometry of the pitch curve. The study is virtually developed, in AutoCAD environment, by animating and investigating the gear solid models in mesh. The tooth static contact analysis enables the path of contact area and distribution to be evaluated in correlation with the following variable initial data: gear pitch curve geometry, tooth profile geometry, as a consequence of different generating procedures, and the gear pressure angle. It was found out that the noncircular gear tooth contact could be improved by choosing different procedures for the tooth flank generation in concave and convex zones and by increasing the gear pressure angle.

  13. Pitfalls and Precautions When Using Predicted Failure Data for Quantitative Analysis of Safety Risk for Human Rated Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Hatfield, Glen S.; Hark, Frank; Stott, James

    2016-01-01

    Launch vehicle reliability analysis is largely dependent upon using predicted failure rates from data sources such as MIL-HDBK-217F. Reliability prediction methodologies based on component data do not take into account system integration risks such as those attributable to manufacturing and assembly. These sources often dominate component level risk. While consequence of failure is often understood, using predicted values in a risk model to estimate the probability of occurrence may underestimate the actual risk. Managers and decision makers use the probability of occurrence to influence the determination whether to accept the risk or require a design modification. The actual risk threshold for acceptance may not be fully understood due to the absence of system level test data or operational data. This paper will establish a method and approach to identify the pitfalls and precautions of accepting risk based solely upon predicted failure data. This approach will provide a set of guidelines that may be useful to arrive at a more realistic quantification of risk prior to acceptance by a program.

  14. [Adaptation of humans to walking in semi-hard and flexible space suits under terrestrial gravity].

    PubMed

    Panfilov, V E

    2011-01-01

    The spacesuit donning-on procedure can be viewed as the combining of two kinematic circuits into a single human-spacesuit functional system (HSS) for implementation of extravehicular operations. Optimal human-spacesuit interaction hinges on controllability and coordination of HSS mobile components, and also spacesuit slaving to the central nervous system (CNS) mediated through the human locomotion apparatus. Analysis of walking patterns in semi-hard and flexible spacesuits elucidated the direct and feedback relations between the external (spacesuit) and external (locomotion apparatus and CNS) circuits Lack of regularity in the style of spacesuit design creates difficulties for the direct CNS control of locomotion. Consequently, it is necessary to modify the locomotion command program in order to resolve these difficulties and to add flexibility to CNS control The analysis also helped trace algorithm of program modifications with the ultimate result of induced (forced) walk optimization. Learning how to walk in spacesuit Berkut requires no more than 2500 single steps, whereas about 300 steps must be made to master walk skills in spacesuit SKV.

  15. Effects of moderate prenatal ethanol exposure and age on social behavior, spatial response perseveration errors and motor behavior

    PubMed Central

    Hamilton, Derek A.; Barto, Daniel; Rodriguez, Carlos I.; Magcalas, Christy; Fink, Brandi C.; Rice, James P.; Bird, Clark W.; Davies, Suzy; Savage, Daniel D.

    2014-01-01

    Persistent deficits in social behavior are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked deficits in social behavior following moderate prenatal alcohol exposure (PAE) in the rat to functional alterations in the ventrolateral frontal cortex [21]. In addition to social behaviors, the regions comprising the ventrolateral frontal cortex are critical for diverse processes ranging from orofacial motor movements to flexible alteration of behavior in the face of changing consequences. The broader behavioral implications of altered ventrolateral frontal cortex function following moderate PAE have, however, not been examined. In the present study we evaluated the consequences of moderate PAE on social behavior, tongue protrusion, and flexibility in a variant of the Morris water task that required modification of a well-established spatial response. PAE rats displayed deficits in tongue protrusion, reduced flexibility in the spatial domain, increased wrestling, and decreased investigation, indicating that several behaviors associated with ventrolateral frontal cortex function are impaired following moderate PAE. A linear discriminant analysis revealed that measures of wrestling and tongue protrusion provided the best discrimination of PAE rats from saccharin-exposed control rats. We also evaluated all behaviors in young adult (4-5 mos.) or older (10-11 mos.) rats to address the persistence of behavioral deficits in adulthood and possible interactions between early ethanol exposure and advancing age. Behavioral deficits in each domain persisted well into adulthood (10-11 mos.), however, there was no evidence that age enhances the effects of moderate PAE within the age ranges that were studied. PMID:24769174

  16. NMR data (ppm) from liver cells exposed to surfactant-wrapped (SDS) and oxidized (-OH) multi-walled carbon nanotubes (MWCNTs)

    EPA Pesticide Factsheets

    Carbon nanotubes (CNTs) have great potential in industrial, consumer, and mechanical applications, based partly on their unique structural, optical and electronic properties. CNTs are commonly oxidized or treated with surfactants to facilitate aqueous solution processing, and these CNT surface modifications also increase possible human and ecological exposures to nanoparticle-contaminated waters. To determine the exposure outcomes of oxidized and surfactant-wrapped multiwalled carbon nanotubes (MWCNTs) on biochemical processes, metabolomics based profiling of human liver cells (C3A) was utilized. Cells were exposed to 0, 10, or 100 ng/mL of MWCNTs for 24 and 48 hr. MWCNT particle size distribution, charge, and aggregation were monitored concurrently during exposures. Following MWCNT exposure, cellular metabolites were extracted, lyophilized, and buffered for 1H NMR analysis. Acquired spectra were subjected to both multivariate and univariate analysis to determine the consequences of nanotube exposure on the metabolite profile of C3A cells. Resulting scores plots illustrated temporal and dose-dependent metabolite responses to all MWCNTs tested. Loadings plots coupled with t-test filtered spectra identified metabolites of interest. XPS analysis revealed the presence of hydroxyl and carboxyl functionalities on both MWCNTs surfaces. Metal content analysis by ICP-AES indicated that the total mass concentration of the potentially toxic impurities in the exposure exper

  17. Molecular recognition of a model globular protein apomyoglobin by synthetic receptor cyclodextrin: effect of fluorescence modification of the protein and cavity size of the receptor in the interaction.

    PubMed

    Saha, Ranajay; Rakshit, Surajit; Pal, Samir Kumar

    2013-11-01

    Labelling of proteins with some extrinsic probe is unavoidable in molecular biology research. Particularly, spectroscopic studies in the optical region require fluorescence modification of native proteins by attaching polycyclic aromatic fluoroprobe with the proteins under investigation. Our present study aims to address the consequence of the attachment of a fluoroprobe at the protein surface in the molecular recognition of the protein by selectively small model receptor. A spectroscopic study involving apomyoglobin (Apo-Mb) and cyclodextrin (CyD) of various cavity sizes as model globular protein and synthetic receptors, respectively, using steady-state and picosecond-resolved techniques, is detailed here. A study involving Förster resonance energy transfer, between intrinsic amino acid tryptophan (donor) and N, N-dimethyl naphthalene moiety of the extrinsic dansyl probes at the surface of Apo-Mb, precisely monitor changes in donor acceptor distance as a consequence of interaction of the protein with CyD having different cavity sizes (β and γ variety). Molecular modelling studies on the interaction of tryptophan and dansyl probe with β-CyD is reported here and found to be consistent with the experimental observations. In order to investigate structural aspects of the interacting protein, we have used circular dichroism spectroscopy. Temperature-dependent circular dichroism studies explore the change in the secondary structure of Apo-Mb in association with CyD, before and after fluorescence modification of the protein. Overall, the study well exemplifies approaches to protein recognition by CyD as a synthetic receptor and offers a cautionary note on the use of hydrophobic fluorescent labels for proteins in biochemical studies involving recognition of molecules. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Surface layer modification of ion bombarded HDPE

    NASA Astrophysics Data System (ADS)

    Bielinski, D.; Lipinski, P.; Slusarski, L.; Grams, J.; Paryjczak, T.; Jagielski, J.; Turos, A.; Madi, N. K.

    2004-08-01

    Press-moulded, high density polyethylene (HDPE) samples were subjected to ion bombardment and effects of the modification studied. He + ions of energy 100 keV or Ar + ions of energy 130 keV were applied in the range of dose 1-30 × 10 15/cm 2 or 1-100 × 10 14/cm 2, respectively. This paper has been focused on structural changes of the surface layer. The consequences of the modification were studied with TOF-SIMS and FTIR-IRS techniques. The results point on two mechanisms taking place simultaneously: ionization of polymer macromolecules and chain scission--resulting in creation of macroradicals. Both of them produce oxidation and lead to significant release of hydrogen. The former diminishes for the highest ion doses, however, creation of molecular oxygen cannot be excluded. The latter in the case of Ar + ion bombardment is reflected by prevailing degradation of the surface layer of HDPE. Contrary to the effect of heavy ions, He + ion bombardment was found to produce significant increase of the material hardness, which was explained by crosslinking of polyethylene. A mechanism of polyacetylene formation, proceeding finally to cross-polymerization of the polymer was proposed. Apart from structural changes, the modification revealed additionally a possibility to improve the wettability of the polymer.

  19. Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy.

    PubMed

    Colussi, Claudia; Gurtner, Aymone; Rosati, Jessica; Illi, Barbara; Ragone, Gianluca; Piaggio, Giulia; Moggio, Maurizio; Lamperti, Costanza; D'Angelo, Grazia; Clementi, Emilio; Minetti, Giulia; Mozzetta, Chiara; Antonini, Annalisa; Capogrossi, Maurizio C; Puri, Pier Lorenzo; Gaetano, Carlo

    2009-07-01

    The present study provides evidence that abnormal patterns of global histone modification are present in the skeletal muscle nuclei of mdx mice and Duchenne muscular dystrophy (DMD) patients. A combination of specific histone H3 modifications, including Ser-10 phosphorylation, acetylation of Lys 9 and 14, and Lys 79 methylation, were found enriched in muscle biopsies from human patients affected by DMD and in late-term fetuses, early postnatal pups, or adult mdx mice. In this context, chromatin immunoprecipitation experiments showed an enrichment of these modifications at the loci of genes involved in proliferation or inflammation, suggesting a regulatory effect on gene expression. Remarkably, the reexpression of dystrophin induced by gentamicin treatment or the administration of nitric oxide (NO) donors reversed the abnormal pattern of H3 histone modifications. These findings suggest an unanticipated link between the dystrophin-activated NO signaling and the remodeling of chromatin. In this context, the regulation of class IIa histone deacetylases (HDACs) 4 and 5 was found altered as a consequence of the reduced NO-dependent protein phosphatase 2A activity, indicating that both NO and class IIa HDACs are important for satellite cell differentiation and gene expression in mdx mice. In conclusion, this work provides the first evidence of a role for NO as an epigenetic regulator in DMD.

  20. Enzymatic modification of a model homogalacturonan with the thermally tolerant pectin methylesterase from Citrus: 1. Nanostructural characterization, enzyme mode of action, and effect of pH.

    PubMed

    Cameron, Randall G; Luzio, Gary A; Vasu, Prasanna; Savary, Brett J; Williams, Martin A K

    2011-03-23

    Methyl ester distribution in pectin homogalacturonan has a major influence on functionality. Enzymatic engineering of the pectin nanostructure for tailoring functionality can expand the role of pectin as a food-formulating agent and the use of in situ modification in prepared foods. We report on the mode of action of a unique citrus thermally tolerant pectin methylesterase (TT-PME) and the nanostructural modifications that it produces. The enzyme was used to produce a controlled demethylesterification series from a model homogalacturonan. Oligogalacturonides released from the resulting demethylesterified blocks introduced by TT-PME using a limited endopolygalacturonase digestion were separated and quantified by high-pressure anion-exchange chromatography (HPAEC) coupled to an evaporative light-scattering detector (ELSD). The results were consistent with the predictions of a numerical simulation, which assumed a multiple-attack mechanism and a degree of processivity ∼10, at both pH 4.5 and 7.5. The average demethylesterified block size (0.6-2.8 nm) and number of average-sized blocks per molecule (0.8-1.9) differed, depending upon pH of the enzyme treatment. The mode of action of this enzyme and consequent nanostructural modifications of pectin differ from a previously characterized citrus salt-independent pectin methylesterase (SI-PME).

  1. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    NASA Astrophysics Data System (ADS)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH induced relevant quanti-tative variations of TSH-receptor, sphingomyelinase and sphingomyelin-synthase, probably due to membrane microdomain structure modifications which in turn, as it occurs in vitro, influence the cellular response to TSH treatment.

  2. Multiscale analysis of bamboo deformation mechanisms following NaOH treatment using X-ray and correlative microscopy.

    PubMed

    Salvati, E; Brandt, L R; Uzun, F; Zhang, H; Papadaki, C; Korsunsky, A M

    2018-05-01

    For hundreds of years, bamboo has been employed for a variety of applications ranging from load-bearing structures to textiles. Thanks to its hierarchical structure that is functionally graded and naturally optimised, bamboo displays a variation in properties across its stem that ensures exceptional flexural performance. Often, alkaline solutions are employed for the treatment of bamboo in order to alter its natural elastic behaviour and make it suitable for particular applications. In this work we study the effect of NaOH solutions of five different concentrations (up to 25%) on the elastic properties of bamboo. By exploiting the capabilities of modern experimental techniques such as in situ synchrotron X-ray scattering and Digital Image Correlation, we present detailed analysis of the deformation mechanisms taking place in the main constituents of bamboo, i.e. fibres and matrix (Parenchyma). The principal achievement of this study is the elucidation of the deformation mechanisms at the fibre scale, where the relative sliding of fibrils plays a crucial role in the property modification of the whole bamboo stem. Furthermore, we shed light on the parenchyma toughness variation as a consequence of alkali treatments. Alkaline solutions are often employed for the treatment of bamboo in order to alter its natural elastic behaviour. In this work we study the effect of alkaline solutions on the elastic properties of bamboo. Using state of the art experimental techniques allowed shedding light on the deformation mechanisms occurring in the bamboo main constituents, i.e. fibres and matrix (parenchyma cells). Enhancement of fibre stiffness was experienced when up to 20% NaOH solution was employed, while for higher concentration a decay was observed. This effect was imputed to the modification of adhesion between fibrils induced by disruption of ligand elements (e.g. lignin). Modification of the matrix toughness was also experienced, that indicated an improved resistance to cracking when the concentration of NaOH is 25%, while reduction of toughness was revealed for lower concentrations. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Dealing with delays does not transfer across sensorimotor tasks.

    PubMed

    de la Malla, Cristina; López-Moliner, Joan; Brenner, Eli

    2014-10-09

    It is known that people can learn to deal with delays between their actions and the consequences of such actions. We wondered whether they do so by adjusting their anticipations about the sensory consequences of their actions or whether they simply learn to move in certain ways when performing specific tasks. To find out, we examined details of how people learn to intercept a moving target with a cursor that follows the hand with a delay and examined the transfer of learning between this task and various other tasks that require temporal precision. Subjects readily learned to intercept the moving target with the delayed cursor. The compensation for the delay generalized across modifications of the task, so subjects did not simply learn to move in a certain way in specific circumstances. The compensation did not generalize to completely different timing tasks, so subjects did not generally expect the consequences of their motor commands to be delayed. We conclude that people specifically learn to control the delayed visual consequences of their actions to perform certain tasks. © 2014 ARVO.

  4. The role of SUMOylation in ageing and senescent decline.

    PubMed

    Princz, Andrea; Tavernarakis, Nektarios

    2017-03-01

    Posttranslational protein modifications are playing crucial roles in essential cellular mechanisms. SUMOylation is a reversible posttranslational modification of specific target proteins by the attachment of a small ubiquitin-like protein. Although the mechanism of conjugation of SUMO to proteins is analogous to ubiquitination, it requires its own, specific set of enzymes. The consequences of SUMOylation are widely variable, depending on the physiological state of the cell and the attached SUMO isoform. Accumulating recent findings have revealed a prominent role of SUMOylation in molecular pathways that govern senescence and ageing. Here, we review the link between SUMO attachment events and cellular processes that influence senescence and ageing, including promyelocytic leukaemia (PML) nuclear body and telomere function, autophagy, reactive oxygen species (ROS) homeostasis and growth factor signalling. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Explosive Products EOS: Adjustment for detonation speed and energy release

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

    Menikoff, Ralph

    2014-09-05

    Propagating detonation waves exhibit a curvature effect in which the detonation speed decreases with increasing front curvature. The curvature effect is due to the width of the wave profile. Numerically, the wave profile depends on resolution. With coarse resolution, the wave width is too large and results in a curvature effect that is too large. Consequently, the detonation speed decreases as the cell size is increased. We propose a modification to the products equation of state (EOS) to compensate for the effect of numerical resolution; i.e., to increase the CJ pressure in order that a simulation propagates a detonation wavemore » with a speed that is on average correct. The EOS modification also adjusts the release isentrope to correct the energy release.« less

  6. Not just gene expression: 3D implications of chromatin modifications during sexual plant reproduction.

    PubMed

    Dukowic-Schulze, Stefanie; Liu, Chang; Chen, Changbin

    2018-01-01

    DNA methylation and histone modifications are epigenetic changes on a DNA molecule that alter the three-dimensional (3D) structure locally as well as globally, impacting chromatin looping and packaging on a larger scale. Epigenetic marks thus inform higher-order chromosome organization and placement in the nucleus. Conventional epigenetic marks are joined by chromatin modifiers like cohesins, condensins and membrane-anchoring complexes to support particularly 3D chromosome organization. The most popular consequences of epigenetic modifications are gene expression changes, but chromatin modifications have implications beyond this, particularly in actively dividing cells and during sexual reproduction. In this opinion paper, we will focus on epigenetic mechanisms and chromatin modifications during meiosis as part of plant sexual reproduction where 3D management of chromosomes and re-organization of chromatin are defining features and prime tasks in reproductive cells, not limited to modulating gene expression. Meiotic chromosome organization, pairing and synapsis of homologous chromosomes as well as distribution of meiotic double-strand breaks and resulting crossovers are presumably highly influenced by epigenetic mechanisms. Special mobile small RNAs have been described in anthers, where these so-called phasiRNAs seem to direct DNA methylation in meiotic cells. Intriguingly, many of the mentioned developmental processes make use of epigenetic changes and small RNAs in a manner other than gene expression changes. Widening our approaches and opening our mind to thinking three-dimensionally regarding epigenetics in plant development holds high promise for new discoveries and could give us a boost for further knowledge.

  7. New Insights Into Roles of Ubiquitin Modification in Regulating Plastids and Other Endosymbiotic Organelles.

    PubMed

    Broad, W; Ling, Q; Jarvis, P

    2016-01-01

    Recent findings have revealed important and diverse roles for the ubiquitin modification of proteins in the regulation of endosymbiotic organelles, which include the primary plastids of plants as well as complex plastids: the secondary endosymbiotic organelles of cryptophytes, alveolates, stramenopiles, and haptophytes. Ubiquitin modifications have a variety of potential consequences, both to the modified protein itself and to cellular regulation. The ubiquitin-proteasome system (UPS) can target individual proteins for selective degradation by the cytosolic 26S proteasome. Ubiquitin modifications can also signal the removal of whole endosymbiotic organelles, for example, via autophagy as has been well characterized in mitochondria. As plastids must import over 90% of their proteins from the cytosol, the observation that the UPS selectively targets the plastid protein import machinery is particularly significant. In this way, the UPS may influence the development and interconversions of different plastid types, as well as plastid responses to stress, by reconfiguring the organellar proteome. In complex plastids, the Symbiont-derived ERAD-Like Machinery (SELMA) has coopted the protein transport capabilities of the ER-Associated Degradation (ERAD) system, whereby misfolded proteins are retrotranslocated from ER for proteasomal degradation, uncoupling them from proteolysis: SELMA components have been retargeted to the second outermost plastid membrane to mediate protein import. In spite of this wealth of new information, there still remain a large number of unanswered questions and a need to define the roles of ubiquitin modification further in the regulation of plastids. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.

    PubMed

    Rispoli, Mandy; Brodhead, Matthew; Wolfe, Katie; Gregori, Emily

    2018-05-01

    Research on trial-based functional analysis has primarily focused on socially maintained challenging behaviors. However, procedural modifications may be necessary to clarify ambiguous assessment results. The purposes of this study were to evaluate the utility of iterative modifications to trial-based functional analysis on the identification of putative reinforcement and subsequent treatment for vocal scripting. For all participants, modifications to the trial-based functional analysis identified a primary function of automatic reinforcement. The structure of the trial-based format led to identification of social attention as an abolishing operation for vocal scripting. A noncontingent attention treatment was evaluated using withdrawal designs for each participant. This noncontingent attention treatment resulted in near zero levels of vocal scripting for all participants. Implications for research and practice are presented.

  9. 40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

  10. 40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

  11. 40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

  12. 40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

  13. Tools for phospho- and glycoproteomics of plasma membranes.

    PubMed

    Wiśniewski, Jacek R

    2011-07-01

    Analysis of plasma membrane proteins and their posttranslational modifications is considered as important for identification of disease markers and targets for drug treatment. Due to their insolubility in water, studying of plasma membrane proteins using mass spectrometry has been difficult for a long time. Recent technological developments in sample preparation together with important improvements in mass spectrometric analysis have facilitated analysis of these proteins and their posttranslational modifications. Now, large scale proteomic analyses allow identification of thousands of membrane proteins from minute amounts of sample. Optimized protocols for affinity enrichment of phosphorylated and glycosylated peptides have set new dimensions in the depth of characterization of these posttranslational modifications of plasma membrane proteins. Here, I summarize recent advances in proteomic technology for the characterization of the cell surface proteins and their modifications. In the focus are approaches allowing large scale mapping rather than analytical methods suitable for studying individual proteins or non-complex mixtures.

  14. Continued urbanization of the United States is causing the deterioration of the central city; costly suburban developments; and increases in congestion, pollution, crime, violence and alienation

    NASA Technical Reports Server (NTRS)

    1975-01-01

    It is shown that urban sprawl and the abuses of technological industries result in substantial environmental and economic costs at the expense of center city locations and populations. Socioeconomic deterioration and modification of the biosphere triggers climatic and environmental changes leading to ecosystem damage and destruction, health consequences and international conflict.

  15. Thyroid function, Alzheimer's disease and postoperative cognitive dysfunction: a tale of dangerous liaisons?

    PubMed

    Mafrica, Federica; Fodale, Vincenzo

    2008-05-01

    Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. Moreover, thyroid hormones negatively regulate expression of the amyloid-beta protein precursor (AbetaPP), which plays a key role in the development of AD. A condition, the so called euthyroid sick syndrome (ESS), characterized by reduced serum T_{3} and T_{4} concentrations without increased serum thyroid stimulation hormone secretion, occurs within hours after major surgery. After surgery, elderly patients often exhibit a transient, reversible state of cognitive alterations. Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.

  16. Associations among child abuse, mental health, and epigenetic modifications in the proopiomelanocortin gene (POMC): A study with children in Tanzania.

    PubMed

    Hecker, Tobias; Radtke, Karl M; Hermenau, Katharin; Papassotiropoulos, Andreas; Elbert, Thomas

    2016-11-01

    Child abuse is associated with a number of emotional and behavioral problems. Nevertheless, it has been argued that these adverse consequences may not hold for societies in which many of the specific acts of abuse are culturally normed. Epigenetic modifications in the genes of the hypothalamus-pituitary-adrenal axis may provide a potential mechanism translating abuse into altered gene expression, which subsequently results in behavioral changes. Our investigation took place in Tanzania, a society in which many forms of abuse are commonly employed as disciplinary methods. We included 35 children with high exposure and compared them to 25 children with low exposure. Extreme group comparisons revealed that children with high exposure reported more mental health problems. Child abuse was associated with differential methylation in the proopiomelanocortin gene (POMC), measured both in saliva and in blood. Hierarchical clustering based on the methylation of the POMC gene found two distinct clusters. These corresponded with children's self-reported abuse, with two-thirds of the children allocated into their respective group. Our results emphasize the consequences of child abuse based on both molecular and behavioral grounds, providing further evidence that acts of abuse affect children, even when culturally acceptable. Furthermore, on a molecular level, our findings strengthen the credibility of children's self-reports.

  17. Quantifying structural modifications of gills of two fish species Astyanax altiparanae (Lambari) and Prochilodus lineatus (Curimbatá) after exposure to biodegradable detergents in urban lake water.

    PubMed

    Fiorelini Pereira, Bruno; Alves, Anderson Luis; Senhorini, José Augusto; Hakime Scalize, Priscilla; Tocchini De Figueiredo, Fellipe Augusto; Pitol, Dimítrius Leonardo; Caetano, Flávio Henrique

    2017-01-01

    Anthropic actions in rivers and urban lakes are a cause for concern to our ecosystem. The effects on fauna and flora of substances discharged into waterways have become a focus for investigations globally. Biodegradable detergents are widely used in residences and small industries, but little is known regarding the consequences on fish fauna. The objective of the present study was to identify modifications in gill structure in two fish species, Astyanax altiparanae and Prochilodus lineatus, after treatment with water obtained from an urban lake and an exposure to 1 ppm diluted biodegradable detergents (linear alkylbenzene sulfonate). Data demonstrated exposure to urban lake produced various alterations in gill functions such as lamellar fusions, aneurysms, mucous, and chlorine cell proliferation, which may be attributed to the presence of detergents in the water but may also be a consequence of synergetic actions of detergents with other pollutants. Results showed that the levels of NO - 2 , Na, F - , Cl - , and Fe were significantly higher in urban lake water but in the presence of detergents Ni was also detected. Evidence indicates that biodegradable detergents produce damage to gill functions, which subsequently alters the fish physiology and reduces the ability to cope with stress and survival.

  18. Modifications Of Hydrostatic-Bearing Computer Program

    NASA Technical Reports Server (NTRS)

    Hibbs, Robert I., Jr.; Beatty, Robert F.

    1991-01-01

    Several modifications made to enhance utility of HBEAR, computer program for analysis and design of hydrostatic bearings. Modifications make program applicable to more realistic cases and reduce time and effort necessary to arrive at a suitable design. Uses search technique to iterate on size of orifice to obtain required pressure ratio.

  19. The Modification of Compounds by Attributive Adjectives

    ERIC Educational Resources Information Center

    Berg, Thomas

    2011-01-01

    This paper examines the modification of nominal compounds by attributive adjectives in English. It draws on a distinction between compound-external (i.e. syntactic) and compound-internal (i.e. morphological) modification. An analysis is presented of more than 1000 pertinent cases, which are roughly equally divided into two-, three- and four-noun…

  20. Quantification of Lysine Acetylation and Succinylation Stoichiometry in Proteins Using Mass Spectrometric Data-Independent Acquisitions (SWATH)

    DOE PAGES

    Meyer, Jesse G.; D’Souza, Alexandria K.; Sorensen, Dylan J.; ...

    2016-09-02

    Post-translational modification of lysine residues by N ε-acylation is an important regulator of protein function. Many large-scale protein acylation studies have assessed relative changes of lysine acylation sites after antibody enrichment using mass spectrometry-based proteomics. Although relative acylation fold-changes are important, this does not reveal site occupancy, or stoichiometry, of individual modification sites, which is critical to understand functional consequences. Recently, methods for determining lysine acetylation stoichiometry have been proposed based on ratiometric analysis of endogenous levels to those introduced after quantitative per-acetylation of proteins using stable isotope-labeled acetic anhydride. However, in our hands, we find that these methods canmore » overestimate acetylation stoichiometries because of signal interferences when endogenous levels of acylation are very low, which is especially problematic when using MS1 scans for quantification. In this study, we sought to improve the accuracy of determining acylation stoichiometry using data-independent acquisition (DIA). Specifically, we use SWATH acquisition to comprehensively collect both precursor and fragment ion intensity data. The use of fragment ions for stoichiometry quantification not only reduces interferences but also allows for determination of site-level stoichiometry from peptides with multiple lysine residues. We also demonstrate the novel extension of this method to measurements of succinylation stoichiometry using deuterium-labeled succinic anhydride. Proof of principle SWATH acquisition studies were first performed using bovine serum albumin for both acetylation and succinylation occupancy measurements, followed by the analysis of more complex samples of E. coli cell lysates. Although overall site occupancy was low (<1%), some proteins contained lysines with relatively high acetylation occupancy.« less

  1. Modifications to the accuracy assessment analysis routine MLTCRP to produce an output file

    NASA Technical Reports Server (NTRS)

    Carnes, J. G.

    1978-01-01

    Modifications are described that were made to the analysis program MLTCRP in the accuracy assessment software system to produce a disk output file. The output files produced by this modified program are used to aggregate data for regions greater than a single segment.

  2. A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding.

    PubMed

    Lin, Ying-Ting

    2013-04-30

    A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis.

  3. Prediction of Protein Modification Sites of Pyrrolidone Carboxylic Acid Using mRMR Feature Selection and Analysis

    PubMed Central

    Zheng, Lu-Lu; Niu, Shen; Hao, Pei; Feng, KaiYan; Cai, Yu-Dong; Li, Yixue

    2011-01-01

    Pyrrolidone carboxylic acid (PCA) is formed during a common post-translational modification (PTM) of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR) and incremental feature selection (IFS). We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations. PMID:22174779

  4. Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition

    PubMed Central

    Sterns, J. David; Smith, Colin B.; Steele, John R.; Stevenson, Kimberly L.; Gallicano, G. Ian

    2014-01-01

    Type II diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels. While the onset of T2DM is known to be the consequence of a multifactorial interplay with a strong genetic component, emerging research has demonstrated the additional role of a variety of epigenetic mechanisms in the development of this disorder. Heritable epigenetic modifications, such as DNA methylation and histone modifications, play a vital role in many important cellular processes, including pancreatic cellular differentiation and maintenance of normal β-cell function. Recent studies have found possible epigenetic mechanisms to explain observed risk factors, such as altered atherogenic lipid profiles, elevated body mass index (BMI), and impaired glucose tolerance (IGT), for later development of T2DM in children born to mothers experiencing both famine and hyperglycemic conditions. It is suggested that these epigenetic influences happen early during gestation and are less susceptible to the effects of postnatal environmental modification as was previously thought, highlighting the importance of early preventative measures in minimizing the global burden of T2DM. PMID:25364722

  5. Contact engineering for efficient charge injection in organic transistors with low-cost metal electrodes

    NASA Astrophysics Data System (ADS)

    Panigrahi, D.; Kumar, S.; Dhar, A.

    2017-10-01

    Controlling charge injection at the metal-semiconductor interface is very crucial for organic electronic devices in general as it can significantly influence the overall device performance. Herein, we report a facile, yet efficient contact modification approach, to enhance the hole injection efficiency through the incorporation of a high vacuum deposited TPD [N,N'-Bis(3-methylphenyl)-N,N'-diphenylbenzidine] interlayer between the electrodes and the active semiconducting layer. The device performance parameters such as mobility and on/off ratio improved significantly after the inclusion of the TPD buffer layer, and more interestingly, the devices with cost effective Ag and Cu electrodes were able to exhibit a superior device performance than the typically used Au source-drain devices. We have also observed that this contact modification technique can be even more effective than commonly used metal oxide interface modifying layers. Our investigations demonstrate the efficacy of the TPD interlayer in effectively reducing the interfacial contact resistance through the modification of pentacene energy levels, which consequently results in the substantial improvement in the device performances.

  6. A Novel Post-translational Modification of Nucleolin, SUMOylation at Lys-294, Mediates Arsenite-induced Cell Death by Regulating gadd45α mRNA Stability*

    PubMed Central

    Zhang, Dongyun; Liang, Yuguang; Xie, Qipeng; Gao, Guangxun; Wei, Jinlong; Huang, Haishan; Li, Jingxia; Gao, Jimin; Huang, Chuanshu

    2015-01-01

    Nucleolin is a ubiquitously expressed protein and participates in many important biological processes, such as cell cycle regulation and ribosomal biogenesis. The activity of nucleolin is regulated by intracellular localization and post-translational modifications, including phosphorylation, methylation, and ADP-ribosylation. Small ubiquitin-like modifier (SUMO) is a category of recently verified forms of post-translational modifications and exerts various effects on the target proteins. In the studies reported here, we discovered SUMOylational modification of human nucleolin protein at Lys-294, which facilitated the mRNA binding property of nucleolin by maintaining its nuclear localization. In response to arsenic exposure, nucleolin-SUMO was induced and promoted its binding with gadd45α mRNA, which increased gadd45α mRNA stability and protein expression, subsequently causing GADD45α-mediated cell death. On the other hand, ectopic expression of Mn-SOD attenuated the arsenite-generated superoxide radical level, abrogated nucleolin-SUMO, and in turn inhibited arsenite-induced apoptosis by reducing GADD45α expression. Collectively, our results for the first time demonstrate that nucleolin-SUMO at K294R plays a critical role in its nucleus sequestration and gadd45α mRNA binding activity. This novel biological function of nucleolin is distinct from its conventional role as a proto-oncogene. Therefore, our findings here not only reveal a new modification of nucleolin protein and its novel functional paradigm in mRNA metabolism but also expand our understanding of the dichotomous roles of nucleolin in terms of cancer development, which are dependent on multiple intracellular conditions and consequently the appropriate regulations of its modifications, including SUMOylation. PMID:25561743

  7. 40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... consequence analysis data elements. 1400.5 Section 1400.5 Protection of Environment ENVIRONMENTAL PROTECTION...

  8. 40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... consequence analysis data elements. 1400.5 Section 1400.5 Protection of Environment ENVIRONMENTAL PROTECTION...

  9. 40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... consequence analysis data elements. 1400.5 Section 1400.5 Protection of Environment ENVIRONMENTAL PROTECTION...

  10. The impact of applied behavior analysis on diverse areas of research.

    PubMed Central

    Kazdin, A E

    1975-01-01

    The impact of applied behavior analysis on various disciplines and areas of research was assessed through two major analyses. First, the relationship of applied behavior analysis to the general area of "behavior modification" was evaluated by examining the citation characteristics of journal articles in JABA and three other behavior-modification journals. Second, the penetration of applied behavior analysis into diverse areas and disciplines, including behavior modification, psychiatry, clinical psychology, education, special education, retardation, speech and hearing, counselling, and law enforcement and correction was assessed. Twenty-five journals representing diverse research areas were evaluated from 1968 to 1974 to assess the extent to which operant techniques were applied for therapeutic, rehabilitative, and educative purposes and the degree to which methodological desiderata of applied behavior analysis were met. The analyses revealed diverse publication outlets for applied behavior analysis in various disciplines. PMID:1184488

  11. WIPP Hazardous Waste Facility Permit Update

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

    Kehrman, B.; Most, W.

    2006-07-01

    The Waste Isolation Pilot Plant (WIPP) Hazardous Waste Facility Permit (HWFP) was issued on October 27, 1999 [1]. Since that time, the WIPP has sought modifications to clarify the permit language, provide alternative methods for meeting permit requirements and to update permit conditions. Significant advancements have been made in transuranic (TRU) waste management as the result of modifications to the HWFP. Among these advancements is a modification to obtain a drum age criteria (DAC) value to perform headspace gas sampling on drums to be super-compacted and placed in a 100-gallon overpack drum. In addition, the Section 311 permit modification requestmore » that would allow for more efficient waste characterization, and the modification to authorize the shipment and disposal of Remote-Handled (RH) TRU waste were merged together and submitted to the regulator as the Consolidated Permit Modification Request (PMR). The submittal of the Consolidated PMR came at the request of the regulator as part of responses to Notices of Deficiency (NODs) for the separate PMRs which had been submitted in previous years. Section 311 of the fiscal year 2004 Energy and Water Developments Appropriations Act (Public Law 108-137) [2] directs the Department of Energy to submit a permit modification that limits waste confirmation to radiography or visual examination of a statistical subpopulation of containers. Section 311 also specifically directs that disposal room performance standards be to be met by monitoring for volatile organic compounds in the underground disposal rooms. This statute translates into the elimination of other waste confirmation methods such as headspace gas sampling and analysis and solids sampling and analysis. These methods, as appropriate, will continue to be used by the generator sites during hazardous waste determinations or characterization activities. This modification is expected to reduce the overall cost of waste analysis by hundreds of millions of dollars [3]. Combining both the chap. 311 and RH TRU waste permit modification requests allows for both the regulator and DOE to expedite action on the modification requests. The Combined PMR reduces costs by having only one administrative process for both modification requests. (authors)« less

  12. Direct Measurement of S-Nitrosothiols with an Orbitrap Fusion Mass Spectrometer: S-Nitrosoglutathione Reductase as a Model Protein.

    PubMed

    Guerra, Damian; Truebridge, Ian; Eyles, Stephen J; Treffon, Patrick; Vierling, Elizabeth

    2018-01-01

    Recent studies suggest cysteine S-nitrosation of S-nitrosoglutathione reductase (GSNOR) could regulate protein redox homeostasis. "Switch" assays enable discovery of putatively S-nitrosated proteins. However, with few exceptions, researchers have not examined the kinetics and biophysical consequences of S-nitrosation. Methods to quantify protein S-nitrosothiol (SNO) abundance and formation kinetics would bridge this mechanistic gap and allow interpretation of the consequences of specific modifications, as well as facilitate development of specific S-nitrosation inhibitors. Here, we describe a rapid assay to estimate protein SNO abundance with intact protein electrospray ionization mass spectrometry. Originally designed using recombinant GSNOR, these methods are applicable to any purified protein to test for or further study nitrosatable cysteines.

  13. Geomorphology and the Law of Unintended Consequences (Locke, 1691): Lessons from coastal weathering and erosion at Prawle (UK) and Kaikoura (NZ)

    NASA Astrophysics Data System (ADS)

    Mottershead, Derek N.; Stephenson, Wayne J.; Hemmingsen, Maree A.

    2016-07-01

    The sites of two field experiments based on micro-erosion metering, one in UK the other in New Zealand, were independently revisited respectively 33 and 17 years after installation. At both sites natural weathering and erosion processes had been inadvertently interrupted by the experimental works, leading to the development of new microscale landforms. These are interpreted in the context of modifications of the controls on weathering processes, leading to enhanced understanding of the processes themselves. This has lessons for the geomorphologist in maintaining a long-term watching brief over former experimental sites, lest some unintended and potentially beneficial outcome has ensued. This theme is embraced by the Law of Unintended Consequences.

  14. Effect of Sr Additive Amount and Holding Time on Microstructure of A390 Aluminum Alloy

    NASA Astrophysics Data System (ADS)

    Zhang, J. H.; Xing, S. M.; Han, Q. Y.; Guo, Q.; Wang, R. F.

    2017-11-01

    The microstructure of A390 alloy under different Sr additive amounts and holding times was studied by means of direct reading spectrum analysis, energy spectrum analysis, optical microscope and electron microscope. The results show that Sr has a good modification to eutectic Si, while it has a negative effect on primary silicon. The Sr addition will increase the size of primary silicon. When the addition amount of Al-10Sr alloy is 0.6%, the modification of eutectic silicon is the optimum. The Sr has a short incubation period and a fine modification at 10min, but it is more serious burning rate in small furnace smelting, and the modification effect disappears basically after 100min.

  15. Modeling polyvinyl chloride Plasma Modification by Neural Networks

    NASA Astrophysics Data System (ADS)

    Wang, Changquan

    2018-03-01

    Neural networks model were constructed to analyze the connection between dielectric barrier discharge parameters and surface properties of material. The experiment data were generated from polyvinyl chloride plasma modification by using uniform design. Discharge voltage, discharge gas gap and treatment time were as neural network input layer parameters. The measured values of contact angle were as the output layer parameters. A nonlinear mathematical model of the surface modification for polyvinyl chloride was developed based upon the neural networks. The optimum model parameters were obtained by the simulation evaluation and error analysis. The results of the optimal model show that the predicted value is very close to the actual test value. The prediction model obtained here are useful for discharge plasma surface modification analysis.

  16. 40 CFR 68.22 - Offsite consequence analysis parameters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Offsite consequence analysis... PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.22 Offsite consequence analysis parameters. (a) Endpoints. For analyses of offsite consequences, the following endpoints shall be...

  17. A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

    PubMed

    Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

    2016-03-01

    Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

  18. A micro-Raman spectroscopic investigation of leukemic U-937 cells in aged cultures

    NASA Astrophysics Data System (ADS)

    Fazio, Enza; Trusso, Sebastiano; Franco, Domenico; Nicolò, Marco Sebastiano; Allegra, Alessandro; Neri, Fortunato; Musolino, Caterina; Guglielmino, Salvatore P. P.

    2016-04-01

    Recently it has been shown that micro-Raman spectroscopy combined with multivariate analysis is able to discriminate among different types of tissues and tumoral cells by the detection of significant alterations and/or reorganizations of complex biological molecules, such as nucleic acids, lipids and proteins. Moreover, its use, being in principle a non-invasive technique, appears an interesting clinical tool for the evaluation of the therapeutical effects and of the disease progression. In this work we analyzed molecular changes in aged cultures of leukemia model U937 cells with respect to fresh cultures of the same cell line. In fact, structural variations of individual neoplastic cells on aging may lead to a heterogeneous data set, therefore falsifying confidence intervals, increasing error levels of analysis and consequently limiting the use of Raman spectroscopy analysis. We found that the observed morphological changes of U937 cells corresponded to well defined modifications of the Raman contributions in selected spectral regions, where markers of specific functional groups, useful to characterize the cell state, are present. A detailed subcellular analysis showed a change in cellular organization as a function of time, and correlated to a significant increase of apoptosis levels. Besides the aforementioned study, Raman spectra were used as input for principal component analysis (PCA) in order to detect and classify spectral changes among U937 cells.

  19. A Morphospace for Reef Fishes: Elongation Is the Dominant Axis of Body Shape Evolution

    PubMed Central

    Claverie, Thomas; Wainwright, Peter C.

    2014-01-01

    Tropical reef fishes are widely regarded as being perhaps the most morphologically diverse vertebrate assemblage on earth, yet much remains to be discovered about the scope and patterns of this diversity. We created a morphospace of 2,939 species spanning 56 families of tropical Indo-Pacific reef fishes and established the primary axes of body shape variation, the phylogenetic consistency of these patterns, and whether dominant patterns of shape change can be accomplished by diverse underlying changes. Principal component analysis showed a major axis of shape variation that contrasts deep-bodied species with slender, elongate forms. Furthermore, using custom methods to compare the elongation vector (axis that maximizes elongation deformation) and the main vector of shape variation (first principal component) for each family in the morphospace, we showed that two thirds of the families diversify along an axis of body elongation. Finally, a comparative analysis using a principal coordinate analysis based on the angles among first principal component vectors of each family shape showed that families accomplish changes in elongation with a wide range of underlying modifications. Some groups such as Pomacentridae and Lethrinidae undergo decreases in body depth with proportional increases in all body regions, while other families show disproportionate changes in the length of the head (e.g., Labridae), the trunk or caudal region in all combinations (e.g., Pempheridae and Pinguipedidae). In conclusion, we found that evolutionary changes in body shape along an axis of elongation dominates diversification in reef fishes. Changes in shape on this axis are thought to have immediate implications for swimming performance, defense from gape limited predators, suction feeding performance and access to some highly specialized habitats. The morphological modifications that underlie changes in elongation are highly diverse, suggesting a role for a range of developmental processes and functional consequences. PMID:25409027

  20. Meta-Analysis of the Effects of Academic Interventions and Modifications on Student Behavior Outcomes

    ERIC Educational Resources Information Center

    Warmbold-Brann, Kristy; Burns, Matthew K.; Preast, June L.; Taylor, Crystal N.; Aguilar, Lisa N.

    2017-01-01

    The current study examined the effect of academic interventions and modifications on behavioral outcomes in a meta-analysis of 32 single-case design studies. Academic interventions included modifying task difficulty, providing instruction in reading, mathematics, or writing, and contingent reinforcement for academic performance. There was an…

  1. Fish community responses to green tides in shallow estuarine and coastal areas

    NASA Astrophysics Data System (ADS)

    Le Luherne, E.; Réveillac, E.; Ponsero, A.; Sturbois, A.; Ballu, S.; Perdriau, M.; Le Pape, O.

    2016-06-01

    All over the world, numerous bays and estuarine systems that are known to shelter essential fish habitats are experiencing proliferations of green macroalgae known as green tides. Although the processes that enhance green tides in response to nutrient enrichment are well known, their consequences for ecological communities -especially for ichthyofauna- remain poorly studied. To estimate these consequences, this analysis focused on the two types of shallow systems that are experiencing green tides: sandy beaches and estuarine mudflats. In these two systems, macroalgae proliferation and fish community were surveyed along seasonal cycles at control and impacted sites that shared similar physico-chemical parameters and sediment structure. To analyse the consequences of green tides on the fish community, a Before-After Control-Impact approach was used. This approach reveals no difference between fish communities at the control and impacted sites before the macroalgal bloom. Then, it underlines an influence of green tides on the fish community, and this influence varies according to the composition, density and duration of the macroalgal bloom. Indeed, when intertidal systems experienced short proliferation and/or weak density, green tides did not seem to impact the fish community. However, when green macroalgae proliferated in large quantities and/or when the proliferation lasted for long periods, the fish community was significantly affected. These modifications in the fish community led to a significant decrease in fish species diversity and density until fish disappeared from impacted sites at high proliferations. Furthermore, the response of fish species to green tides differed according to their functional guilds. Negative consequences for benthic and marine juvenile fish species were beginning at low proliferations, whereas for pelagic fish species they occurred only at high proliferations. Thus, green tides significantly affect fish habitat suitability because they lead to changes in the composition of the fish community and eventually to the local disappearance of fish at high proliferations.

  2. Procedural error monitoring and smart checklists

    NASA Technical Reports Server (NTRS)

    Palmer, Everett

    1990-01-01

    Human beings make and usually detect errors routinely. The same mental processes that allow humans to cope with novel problems can also lead to error. Bill Rouse has argued that errors are not inherently bad but their consequences may be. He proposes the development of error-tolerant systems that detect errors and take steps to prevent the consequences of the error from occurring. Research should be done on self and automatic detection of random and unanticipated errors. For self detection, displays should be developed that make the consequences of errors immediately apparent. For example, electronic map displays graphically show the consequences of horizontal flight plan entry errors. Vertical profile displays should be developed to make apparent vertical flight planning errors. Other concepts such as energy circles could also help the crew detect gross flight planning errors. For automatic detection, systems should be developed that can track pilot activity, infer pilot intent and inform the crew of potential errors before their consequences are realized. Systems that perform a reasonableness check on flight plan modifications by checking route length and magnitude of course changes are simple examples. Another example would be a system that checked the aircraft's planned altitude against a data base of world terrain elevations. Information is given in viewgraph form.

  3. Influence of Tooth Spacing Error on Gears With and Without Profile Modifications

    NASA Technical Reports Server (NTRS)

    Padmasolala, Giri; Lin, Hsiang H.; Oswald, Fred B.

    2000-01-01

    A computer simulation was conducted to investigate the effectiveness of profile modification for reducing dynamic loads in gears with different tooth spacing errors. The simulation examined varying amplitudes of spacing error and differences in the span of teeth over which the error occurs. The modification considered included both linear and parabolic tip relief. The analysis considered spacing error that varies around most of the gear circumference (similar to a typical sinusoidal error pattern) as well as a shorter span of spacing errors that occurs on only a few teeth. The dynamic analysis was performed using a revised version of a NASA gear dynamics code, modified to add tooth spacing errors to the analysis. Results obtained from the investigation show that linear tip relief is more effective in reducing dynamic loads on gears with small spacing errors but parabolic tip relief becomes more effective as the amplitude of spacing error increases. In addition, the parabolic modification is more effective for the more severe error case where the error is spread over a longer span of teeth. The findings of this study can be used to design robust tooth profile modification for improving dynamic performance of gear sets with different tooth spacing errors.

  4. Single-event burnout of n-p-n bipolar-junction transistors in hybrid DC/DC converters

    NASA Astrophysics Data System (ADS)

    Warren, K.; Roth, D.; Kinnison, J.; Pappalardo, R.

    2002-12-01

    Single-event-induced failure of the Lambda Advanced Analog AMF2805S DC/DC Converter has been traced to burnout of an n-p-n transistor in the MOSFET drive stage. The failures were observed during testing while in inhibit mode only. Modifications to prevent burnout of the drive stage were successfully employed. A discussion of the failure mechanism and consequences for DC/DC converter testing are presented.

  5. Foreword

    NASA Astrophysics Data System (ADS)

    Bergheau, Jean-Michel; Drapier, Sylvain; Feulvarch, Éric; Ponthot, Jean-Philippe

    2016-04-01

    In the face of increasingly fierce global competition, industrial companies must develop products more and more quickly and cheaply. In such a context, the numerical simulation of manufacturing processes is a big challenge and a key factor for success. Indeed, numerical simulation enables the control of manufacturing processes and of the consequences that they induce on the manufactured parts in terms of material modifications, geometrical changes or residual stresses, each of them playing an important role in the lifetime of the component.

  6. Enrichment and separation techniques for large-scale proteomics analysis of the protein post-translational modifications.

    PubMed

    Huang, Junfeng; Wang, Fangjun; Ye, Mingliang; Zou, Hanfa

    2014-11-06

    Comprehensive analysis of the post-translational modifications (PTMs) on proteins at proteome level is crucial to elucidate the regulatory mechanisms of various biological processes. In the past decades, thanks to the development of specific PTM enrichment techniques and efficient multidimensional liquid chromatography (LC) separation strategy, the identification of protein PTMs have made tremendous progress. A huge number of modification sites for some major protein PTMs have been identified by proteomics analysis. In this review, we first introduced the recent progresses of PTM enrichment methods for the analysis of several major PTMs including phosphorylation, glycosylation, ubiquitination, acetylation, methylation, and oxidation/reduction status. We then briefly summarized the challenges for PTM enrichment. Finally, we introduced the fractionation and separation techniques for efficient separation of PTM peptides in large-scale PTM analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Igneous intrusion models for floor fracturing in lunar craters

    NASA Technical Reports Server (NTRS)

    Wichman, R. W.; Schultz, P. H.

    1991-01-01

    Lunar floor-fractured craters are primarily located near the maria and frequently contain ponded mare units and dark mantling deposits. Fracturing is confined to the crater interior, often producing a moat-like feature near the floor edge, and crater depth is commonly reduced by uplift of the crater floor. Although viscous relaxation of crater topography can produce such uplift, the close association of modification with surface volcanism supports a model linking floor fracture to crater-centered igneous intrusions. The consequences of two intrusion models for the lunar interior are quantitatively explored. The first model is based on terrestrial laccoliths and describes a shallow intrusion beneath the crater. The second model is based on cone sheet complexes where surface deformation results from a deeper magma chamber. Both models, their fit to observed crater modifications and possible implications for local volcanism are described.

  8. Modeling the impact of hydromorphological alterations by dams and channelization on fish habitat.

    NASA Astrophysics Data System (ADS)

    Parasiewicz, Piotr; Suska, Katarzyna

    2017-04-01

    As a consequence of introduction of Water Framework Directive it has been discovered that hydromorphological pressures are one of the main causes of impact on aquatic fauna. However, the impact may vary depending on river type and fish community. To test this hypothesis, we modelled alterations of fish habitat on 6 river sections across Poland using MesoHABSIM approach. The original models of habitat for Target Fish Community were based on repeated field surveys in reference river sections, classified into four fish-ecological classes. Introducing to the models three hydromorphological modification types (damming, channelization and dredging) changed persistent habitat availability for the fish community. The change was measured with Habitat Stress Days Alteration index. Overall the modifications caused increase of habitat stress days, but impact varied depending on season, hydromorphologic river type and expected fish community.

  9. Achievement Place: development of the elected manager system1

    PubMed Central

    Phillips, Elery L.; Phillips, Elaine A.; Wolf, Montrose M.; Fixsen, Dean L.

    1973-01-01

    A series of experiments was carried out to compare several administrative systems at Achievement Place, a family style behavior modification program for pre-delinquent boys. One aspect of the motivation system at Achievement Place was the token economy in which the youths could earn or lose points that could be exchanged for privileges. Several arrangements for assigning routine tasks and for providing token consequences for task performance were compared for their effectiveness in accomplishing the tasks and for their preference by the boys. The independent variables studied included: (1) individually assigned tasks versus group assigned tasks; (2) consequences for individual performance versus consequences for group performance; (3) a peer managership that could be earned by the highest bidder versus a peer managership that could be determined democratically by the peers. The results suggested that among those systems studied the system that best met the criteria of effectiveness and preference involved a democratically elected peer manager who had the authority both to give and to take away points for his peers' performances. PMID:16795439

  10. Head-group acylation of monogalactosyldiacylglycerol is a common stress response, but the acyl-galactose acyl composition varies with the plant species and applied stress

    USDA-ARS?s Scientific Manuscript database

    Head group acylation of monogalactosyldiacylglycerol is a plant lipid modification occurring during bacterial infection. Little is known about the range of stresses that induce this lipid modification, the molecular species induced, and the function of the modification. Lipidomic analysis using trip...

  11. The Stability of Post Hoc Model Modifications in Covariance Structure Models.

    ERIC Educational Resources Information Center

    Hutchinson, Susan R.

    The work of R. MacCallum et al. (1992) was extended by examining chance modifications through a Monte Carlo simulation. The stability of post hoc model modifications was examined under varying sample size, model complexity, and severity of misspecification using 2- and 4-factor oblique confirmatory factor analysis (CFA) models with four and eight…

  12. Thermal and flow analysis subroutines for the SINDA-version 9 computer routine

    NASA Technical Reports Server (NTRS)

    Oren, J. A.; Williams, D. R.

    1973-01-01

    Fluid flow analysis, special thermal analysis and input/output capabilities of the MOTAR routine were incorporated into the SINDA routine. All the capabilities were added in the form of user subroutines so that they may be added to different versions of SINDA with a minimum of programmer effort. Two modifications were made to the existing subroutines of SINDA/8 to incorporate the above subroutines. These were: (1) A modification to the preprocessor to permit actual values of array numbers, conductor numbers, node numbers or constant numbers supplied as array data to be converted to relative numbers. (2) Modifications to execution subroutine CNFAST to make it compatible with the radiant interchange user subroutine, RADIR. This modified version of SINDA has been designated SINDA/version 9. A detailed discussion of the methods used for the capabilities added is presented. The modifications for the SINDA subroutines are described, as well as user subroutines. All subroutines added or modified are listed.

  13. Risk analysis of analytical validations by probabilistic modification of FMEA.

    PubMed

    Barends, D M; Oldenhof, M T; Vredenbregt, M J; Nauta, M J

    2012-05-01

    Risk analysis is a valuable addition to validation of an analytical chemistry process, enabling not only detecting technical risks, but also risks related to human failures. Failure Mode and Effect Analysis (FMEA) can be applied, using a categorical risk scoring of the occurrence, detection and severity of failure modes, and calculating the Risk Priority Number (RPN) to select failure modes for correction. We propose a probabilistic modification of FMEA, replacing the categorical scoring of occurrence and detection by their estimated relative frequency and maintaining the categorical scoring of severity. In an example, the results of traditional FMEA of a Near Infrared (NIR) analytical procedure used for the screening of suspected counterfeited tablets are re-interpretated by this probabilistic modification of FMEA. Using this probabilistic modification of FMEA, the frequency of occurrence of undetected failure mode(s) can be estimated quantitatively, for each individual failure mode, for a set of failure modes, and the full analytical procedure. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Aircraft Modifications: Assessing the Current State of Air Force Aircraft Modifications and the Implications for Future Military Capability

    DTIC Science & Technology

    2007-01-25

    Air, Space , and Cyberspace." Introduction 3 group production lots together into ’spirals’ or ’increments’. These groupings, as well as an increased...important reference point for this work. The analysis of the modification process presented in this reserach , however, does help shed light on the...planning efforts. Chapter 7- The Future of Aircraft Modifications "Strategy is the art of making use of time and space . I am less concerned about the

  15. From projected species distribution to food-web structure under climate change.

    PubMed

    Albouy, Camille; Velez, Laure; Coll, Marta; Colloca, Francesco; Le Loc'h, François; Mouillot, David; Gravel, Dominique

    2014-03-01

    Climate change is inducing deep modifications in species geographic ranges worldwide. However, the consequences of such changes on community structure are still poorly understood, particularly the impacts on food-web properties. Here, we propose a new framework, coupling species distribution and trophic models, to predict climate change impacts on food-web structure across the Mediterranean Sea. Sea surface temperature was used to determine the fish climate niches and their future distributions. Body size was used to infer trophic interactions between fish species. Our projections reveal that 54 fish species of 256 endemic and native species included in our analysis would disappear by 2080-2099 from the Mediterranean continental shelf. The number of feeding links between fish species would decrease on 73.4% of the continental shelf. However, the connectance of the overall fish web would increase on average, from 0.26 to 0.29, mainly due to a differential loss rate of feeding links and species richness. This result masks a systematic decrease in predator generality, estimated here as the number of prey species, from 30.0 to 25.4. Therefore, our study highlights large-scale impacts of climate change on marine food-web structure with potential deep consequences on ecosystem functioning. However, these impacts will likely be highly heterogeneous in space, challenging our current understanding of climate change impact on local marine ecosystems. © 2013 John Wiley & Sons Ltd.

  16. Surface Modification of Solution-Processed ZrO2 Films through Double Coating for Pentacene Thin-Film Transistors

    NASA Astrophysics Data System (ADS)

    Kwon, Jin-Hyuk; Bae, Jin-Hyuk; Lee, Hyeonju; Park, Jaehoon

    2018-03-01

    We report the modification of surface properties of solution-processed zirconium oxide (ZrO2) dielectric films achieved by using double-coating process. It is proven that the surface properties of the ZrO2 film are modified through the double-coating process; the surface roughness decreases and the surface energy increases. The present surface modification of the ZrO2 film contributes to an increase in grain size of the pentacene film, thereby increasing the field-effect mobility and decreasing the threshold voltage of the pentacene thin-film transistors (TFTs) having the ZrO2 gate dielectric. Herein, the molecular orientation of pentacene film is also studied based on the results of contact angle and X-ray diffraction measurements. Pentacene molecules on the double-coated ZrO2 film are found to be more tilted than those on the single-coated ZrO2 film, which is attributed to the surface modification of the ZrO2 film. However, no significant differences are observed in insulating properties between the single-and the double-coated ZrO2 dielectric films. Consequently, the characteristic improvements of the pentacene TFTs with the double-coated ZrO2 gate dielectric film can be understood through the increase in pentacene grain size and the reduction in grain boundary density.

  17. REDOX REGULATION OF SIRT1 IN INFLAMMATION AND CELLULAR SENESCENCE

    PubMed Central

    Hwang, Jae-woong; Yao, Hongwei; Caito, Samuel; Sundar, Isaac K.; Rahman, Irfan

    2013-01-01

    Sirtuin1 (SIRT1) regulates inflammation, aging (lifespan and healthspan), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. SIRT1 is regulated by a NAD+-dependent DNA repair enzyme poly(ADP-ribose)-polymerase-1 (PARP-1), and subsequent NAD+ depletion by oxidative stresses may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to post-translational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65 and FOXO3, thereby enhancing the inflammatory, pro-senescent and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox post-translational modifications of SIRT1 and its role in PARP1, NF-κB activation, FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging are discussed. Furthermore, we also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases. PMID:23542362

  18. DATAMAP upgrade version 4.0

    NASA Technical Reports Server (NTRS)

    Watts, Michael E.; Dejpour, Shabob R.

    1989-01-01

    The changes made on the data analysis and management program DATAMAP (Data from Aeromechanics Test and Analytics - Management and Analysis Package) are detailed. These changes are made to Version 3.07 (released February, 1981) and are called Version 4.0. Version 4.0 improvements were performed by Sterling Software under contract to NASA Ames Research Center. The increased capabilities instituted in this version include the breakout of the source code into modules for ease of modification, addition of a more accurate curve fit routine, ability to handle higher frequency data, additional data analysis features, and improvements in the functionality of existing features. These modification will allow DATAMAP to be used on more data sets and will make future modifications and additions easier to implement.

  19. Non-destructive analysis of ancient bimetal swords from western Asia by γ-ray radiography and X-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Shizuma, Kiyoshi; Kajimoto, Tsuyoshi; Endo, Satoru; Matsugi, Kazuhiro; Arimatsu, Yui; Nojima, Hisashi

    2017-09-01

    Eight ancient bimetal swords held by Hiroshima University, Japan were analyzed non-destructively through γ-ray radiography and X-ray fluorescence (XRF). 137Cs and 60Co γ-ray irradiation sources were used to obtain transmission images of swords. A scanning radiography method using a 60Co γ-ray source was developed. XRF was used for qualitative elemental analysis of the swords. The presence of iron cores in the hilts of some swords had been observed and it was assumed that the cores were a ritual symbol or had a functional purpose. However, our work reveals that these swords were originally bronze-hilted iron swords and that the rusty blades were replaced with bronze blades to maintain the swords' commercial value as an antique. Consequently, the rest of the iron blade was left in the hilt as an iron tang. The junction of the blade and the guard was soldered and painted to match the patina color. XRF analysis clearly showed that the elemental Sn/Cu ratios of the blades and the hilts were different. These findings are useful for clarifying the later modifications of the swords and are important for interpreting Bronze Age and Iron Age history correctly.

  20. Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood

    PubMed Central

    Harris, Donald G.; Quinn, Kevin J.; French, Beth M.; Schwartz, Evan; Kang, Elizabeth; Dahi, Siamak; Phelps, Carol J.; Ayares, David L.; Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

    2014-01-01

    Background Genetically modified pigs are a promising potential source of lung xenografts. Ex-vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. Methods Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had 1 genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 hours of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. Results Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 hours generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55 or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. Conclusion This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury, and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival. PMID:25470239

  1. Modulation of the specific glutathionylation of mitochondrial proteins in the yeast Saccharomyces cerevisiae under basal and stress conditions.

    PubMed

    Gergondey, Rachel; Garcia, Camille; Marchand, Christophe H; Lemaire, Stephane D; Camadro, Jean-Michel; Auchère, Françoise

    2017-03-15

    The potential biological consequences of oxidative stress and changes in glutathione levels include the oxidation of susceptible protein thiols and reversible covalent binding of glutathione to the -SH groups of proteins by S-glutathionylation. Mitochondria are central to the response to oxidative stress and redox signaling. It is therefore crucial to explore the adaptive response to changes in thiol-dependent redox status in these organelles. We optimized the purification protocol of glutathionylated proteins in the yeast Saccharomyces cerevisiae and present a detailed proteomic analysis of the targets of protein glutathionylation in cells undergoing constitutive metabolism and after exposure to various stress conditions. This work establishes the physiological importance of the glutathionylation process in S. cerevisiae under basal conditions and provides evidence for an atypical and unexpected cellular distribution of the process between the cytosol and mitochondria. In addition, our data indicate that each oxidative condition (diamide, GSSG, H 2 O 2 , or the presence of iron) elicits an adaptive metabolic response affecting specific mitochondrial metabolic pathways, mainly involved in the energetic maintenance of the cells. The correlation of protein modifications with intracellular glutathione levels suggests that protein deglutathionylation may play a role in protecting mitochondria from oxidative stress. This work provides further insights into the diversity of proteins undergoing glutathionylation and the role of this post-translational modification as a regulatory process in the adaptive response of the cell. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  2. Climatic changes, bioclimatic stages and flooding durations in relation with public health

    NASA Astrophysics Data System (ADS)

    Sandoz, A.; Roumieux, C.; Trouillet, A.

    2009-12-01

    Climatic Changes, and more generaly Global Changes, play a major role in environmental modifications related to public health. Modifications of temperatures, precipitations... influence ecological habitats. These habitats can be adapted for some animals species, responsable for predestinate pandemics. Mosquitoes and birds represent for certain pandemics the essential elements of virus transmission. Abundance of mosquitoes and birds species, is heavily conditioned to favorable ecological habitats, flooded areas extent and their variations. The study we carried, has been done in South of France. We show present status of ecological habitats and flooded durations in relation with actual climat. We have refine mediterranean spatial knowledge in mediterranean basin with actual data. We show evolution of climat and consequences for bioclimatic stages, using world clim data and IPCC scenarii. We reach environment impact for certain virus like West Nile virus. This virus affects birds, horses and hands up to men (e.g.West Nile virus appeared in 1999 in USA, between 1999 and 2007 : 27 000 human cases including 1 050 deaths). Presence of the virus is conditioned by different factors, primarily including vector distribution (mosquitoes). We show how it’s possible to localise favorable areas for the virus and to predict its future expansion areas. We present maps of the possibilities for future concerning previsions of bioclimatic steps variations. Thanks to the latest remote sensing and spatial analysis techniques. Our maps may be used as precious tools to help decision makers when faced with mosquito related problems.

  3. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4

    PubMed Central

    Saavedra, Francisco; Rivera, Carlos; Rivas, Elizabeth; Merino, Paola; Garrido, Daniel; Hernández, Sergio; Forné, Ignasi; Vassias, Isabelle; Gurard-Levin, Zachary A.; Alfaro, Iván E.; Imhof, Axel; Almouzni, Geneviève

    2017-01-01

    Abstract Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iβ. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iβ protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iβ depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iβ and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4. PMID:28977641

  4. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4.

    PubMed

    Saavedra, Francisco; Rivera, Carlos; Rivas, Elizabeth; Merino, Paola; Garrido, Daniel; Hernández, Sergio; Forné, Ignasi; Vassias, Isabelle; Gurard-Levin, Zachary A; Alfaro, Iván E; Imhof, Axel; Almouzni, Geneviève; Loyola, Alejandra

    2017-11-16

    Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iβ. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iβ protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iβ depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iβ and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Immune Dysfunction as a Cause and Consequence of Malnutrition.

    PubMed

    Bourke, Claire D; Berkley, James A; Prendergast, Andrew J

    2016-06-01

    Malnutrition, which encompasses under- and overnutrition, is responsible for an enormous morbidity and mortality burden globally. Malnutrition results from disordered nutrient assimilation but is also characterized by recurrent infections and chronic inflammation, implying an underlying immune defect. Defects emerge before birth via modifications in the immunoepigenome of malnourished parents, and these may contribute to intergenerational cycles of malnutrition. This review summarizes key recent studies from experimental animals, in vitro models, and human cohorts, and proposes that immune dysfunction is both a cause and a consequence of malnutrition. Focusing on childhood undernutrition, we highlight gaps in current understanding of immune dysfunction in malnutrition, with a view to therapeutically targeting immune pathways as a novel means to reduce morbidity and mortality. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Correlated topographic and structural modification on Si surface during multi-shot femtosecond laser exposures: Si nanopolymorphs as potential local structural nanomarkers

    NASA Astrophysics Data System (ADS)

    Ionin, A. A.; Kudryashov, S. I.; Levchenko, A. O.; Nguyen, L. V.; Saraeva, I. N.; Rudenko, A. A.; Ageev, E. I.; Potorochin, D. V.; Veiko, V. P.; Borisov, E. V.; Pankin, D. V.; Kirilenko, D. A.; Brunkov, P. N.

    2017-09-01

    High-pressure Si-XII and Si-III nanocrystalline polymorphs, as well as amorphous Si phase, appear consequently during multi-shot femtosecond-laser exposure of crystalline Si wafer surface above its spallation threshold along with permanently developing quasi-regular surface texture (ripples, microcones), residual hydrostatic stresses and subsurface damage, which are characterized by scanning and transmission electron microscopy, as well as by Raman micro-spectroscopy. The consequent yields of these structural Si phases indicate not only their spatially different appearance, but also potentially enable to track nanoscale, transient laser-induced high-pressure, high-temperature physical processes - local variation of ablation mechanism and rate, pressurization/pressure release, melting/resolidification, amorphization, annealing - versus cumulative laser exposure and the related development of the surface topography.

  7. Evaluation of Proteomic Search Engines for the Analysis of Histone Modifications

    PubMed Central

    2015-01-01

    Identification of histone post-translational modifications (PTMs) is challenging for proteomics search engines. Including many histone PTMs in one search increases the number of candidate peptides dramatically, leading to low search speed and fewer identified spectra. To evaluate database search engines on identifying histone PTMs, we present a method in which one kind of modification is searched each time, for example, unmodified, individually modified, and multimodified, each search result is filtered with false discovery rate less than 1%, and the identifications of multiple search engines are combined to obtain confident results. We apply this method for eight search engines on histone data sets. We find that two search engines, pFind and Mascot, identify most of the confident results at a reasonable speed, so we recommend using them to identify histone modifications. During the evaluation, we also find some important aspects for the analysis of histone modifications. Our evaluation of different search engines on identifying histone modifications will hopefully help those who are hoping to enter the histone proteomics field. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD001118. PMID:25167464

  8. Evaluation of proteomic search engines for the analysis of histone modifications.

    PubMed

    Yuan, Zuo-Fei; Lin, Shu; Molden, Rosalynn C; Garcia, Benjamin A

    2014-10-03

    Identification of histone post-translational modifications (PTMs) is challenging for proteomics search engines. Including many histone PTMs in one search increases the number of candidate peptides dramatically, leading to low search speed and fewer identified spectra. To evaluate database search engines on identifying histone PTMs, we present a method in which one kind of modification is searched each time, for example, unmodified, individually modified, and multimodified, each search result is filtered with false discovery rate less than 1%, and the identifications of multiple search engines are combined to obtain confident results. We apply this method for eight search engines on histone data sets. We find that two search engines, pFind and Mascot, identify most of the confident results at a reasonable speed, so we recommend using them to identify histone modifications. During the evaluation, we also find some important aspects for the analysis of histone modifications. Our evaluation of different search engines on identifying histone modifications will hopefully help those who are hoping to enter the histone proteomics field. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD001118.

  9. Rainbow schlieren and its applications

    NASA Technical Reports Server (NTRS)

    Howes, W. L.

    1984-01-01

    In this modification of the schlieren apparatus the knife-edge is replaced by a radial-rainbow filter with a transparent center and opaque surround. Consequently, refractive-index inhomogeneities in the test section appear varicolored, whereas uniformities appear white. The rainbow schlieren is simple, is easy to use, and accentuates detail regarding inhomogeneities more than the ordinary schlieren. The rainbow schlieren permits quantitative evaluation of certain refractive-index distributions, including turbulence, by simple calculations from observations of hue rather than irradiance.

  10. Unexpected consequences of genetic selection in broilers and turkeys: problems and solutions.

    PubMed

    Hocking, P M

    2014-02-01

    1. Genetic theory leads to the expectation that unexpected consequences of genetic selection for production traits will inevitably occur and that these changes are likely to be undesirable. 2. Both artificial selection for production efficiency and "natural" selection for adaptation to the production environment result in selection sweeps that increase the frequencies of rare recessive alleles that have a negative effect on fitness. 3. Fitness is broadly defined as any trait that affects the ability to survive, reproduce and contribute to the next generation, such as musculoskeletal disease in growing broiler chickens and multiple ovulation in adult broiler parents. 4. Welfare concerns about the negative effects of genetic selection on bird welfare are sometimes exaggerated but are nevertheless real. Breeders have paid increasing attention to these traits over several decades and have demonstrated improvement in pedigree flocks. There is an urgent need to monitor changes in commercial flocks to ensure that genetic change is accompanied by improvements in that target population. 5. New technologies for trait measurement, whole genome selection and targeted genetic modification hold out the promise of efficient and rapid improvement of welfare traits in future breeding of broiler chickens and turkeys. The potential of targeted genetic modification for enhancing welfare traits is considerable, but the goal of achieving public acceptability for the progeny of transgenic poultry will be politically challenging.

  11. Radiation-induced reductive modifications of sulfur-containing amino acids within peptides and proteins.

    PubMed

    Chatgilialoglu, Chryssostomos; Ferreri, Carla; Torreggiani, Armida; Salzano, Anna Maria; Renzone, Giovanni; Scaloni, Andrea

    2011-10-19

    The complex scenario of radical stress reactions affecting peptides/proteins can be better elucidated through the design of biomimetic studies simulating the consequences of the different free radicals attacking amino acids. In this context, ionizing radiations allowed to examine the specific damages caused by H-atoms and electrons coupled with protons, thus establishing the molecular basis of reductive radical stress. This is an innovative concept that complements the well-known oxidative stress also in view of a complete understanding of the global consequences of radical species reactivities on living systems. This review summarizes the knowledge of the chemical changes present in sulfur-containing amino acids occurring in polypeptides under reductive radical conditions, in particular the transformation of Met and Cys residues into α-amino butyric acid and alanine, respectively. Reductive radical stress causing a desulfurization process, is therefore coupled with the formation of S-centered radicals, which in turn can diffuse apart and become responsible of the damage transfer from proteins to lipids. These reductive modifications assayed in different peptide/protein sequences constitute an integration of the molecular inventories that up to now take into account only oxidative transformations. They can be useful to achieve an integrated vision of the free radical reactivities in a multifunctional system and, overall, for wider applications in the redox proteomics field. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Modifications to the modular three-dimensional finite-difference ground-water flow model used for the Columbia Plateau Regional Aquifer-System Analysis, Washington, Oregon, and Idaho

    USGS Publications Warehouse

    Hansen, A.J.

    1993-01-01

    The report documents modifications to the U.S. Geological Survey's modular three-dimensional finite-difference ground-water flow model used for a regional aquifer-system analysis of the Columbia Plateau. The report, which describes the concepts and mathematical basis for the modifications, is intended for potential users who are familiar with the original modular model. The modifications permit flow from a layer to any adjacent layer, allow the model to retain a cell of a layer that has been cut completely through by a canyon, and allow placing ground-water flow barriers on only specified branch conductances; a special version of the modified model uses a convergent grid. The report describes the data-input items that this modified model must read.

  13. Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta

    PubMed Central

    Cabral, Wayne A.; Perdivara, Irina; Weis, MaryAnn; Terajima, Masahiko; Blissett, Angela R.; Chang, Weizhong; Perosky, Joseph E.; Makareeva, Elena N.; Mertz, Edward L.; Leikin, Sergey; Tomer, Kenneth B.; Kozloff, Kenneth M.; Eyre, David R.; Yamauchi, Mitsuo; Marini, Joan C.

    2014-01-01

    Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib−/− mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2–11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib−/− fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered crosslink pattern was associated with decreased collagen deposition into matrix in culture, altered fibril structure in tissue, and reduced bone strength. These studies demonstrate novel consequences of the indirect regulatory effect of CyPB on collagen hydroxylation, impacting collagen glycosylation, crosslinking and fibrillogenesis, which contribute to maintaining bone mechanical properties. PMID:24968150

  14. Abnormal type I collagen post-translational modification and crosslinking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta.

    PubMed

    Cabral, Wayne A; Perdivara, Irina; Weis, MaryAnn; Terajima, Masahiko; Blissett, Angela R; Chang, Weizhong; Perosky, Joseph E; Makareeva, Elena N; Mertz, Edward L; Leikin, Sergey; Tomer, Kenneth B; Kozloff, Kenneth M; Eyre, David R; Yamauchi, Mitsuo; Marini, Joan C

    2014-06-01

    Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib-/- mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2-11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib-/- fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered crosslink pattern was associated with decreased collagen deposition into matrix in culture, altered fibril structure in tissue, and reduced bone strength. These studies demonstrate novel consequences of the indirect regulatory effect of CyPB on collagen hydroxylation, impacting collagen glycosylation, crosslinking and fibrillogenesis, which contribute to maintaining bone mechanical properties.

  15. Biomass for thermochemical conversion: targets and challenges

    PubMed Central

    Tanger, Paul; Field, John L.; Jahn, Courtney E.; DeFoort, Morgan W.; Leach, Jan E.

    2013-01-01

    Bioenergy will be one component of a suite of alternatives to fossil fuels. Effective conversion of biomass to energy will require the careful pairing of advanced conversion technologies with biomass feedstocks optimized for the purpose. Lignocellulosic biomass can be converted to useful energy products via two distinct pathways: enzymatic or thermochemical conversion. The thermochemical pathways are reviewed and potential biotechnology or breeding targets to improve feedstocks for pyrolysis, gasification, and combustion are identified. Biomass traits influencing the effectiveness of the thermochemical process (cell wall composition, mineral and moisture content) differ from those important for enzymatic conversion and so properties are discussed in the language of biologists (biochemical analysis) as well as that of engineers (proximate and ultimate analysis). We discuss the genetic control, potential environmental influence, and consequences of modification of these traits. Improving feedstocks for thermochemical conversion can be accomplished by the optimization of lignin levels, and the reduction of ash and moisture content. We suggest that ultimate analysis and associated properties such as H:C, O:C, and heating value might be more amenable than traditional biochemical analysis to the high-throughput necessary for the phenotyping of large plant populations. Expanding our knowledge of these biomass traits will play a critical role in the utilization of biomass for energy production globally, and add to our understanding of how plants tailor their composition with their environment. PMID:23847629

  16. Affective Antecedents of the Perceived Effectiveness of Antidrug Advertisements: An Analysis of Adolescents’ Momentary and Retrospective Evaluations

    PubMed Central

    Vohs, Kathleen D.; Luciana, Monica; Cuthbert, Bruce N.; MacDonald, Angus W.

    2013-01-01

    Perceived message effectiveness is often used as a diagnostic tool to determine whether a health message is likely to be successful or needs modification before use in an intervention. Yet, published research on the antecedents of perceived effectiveness is scarce and, consequently, little is known about why a message is perceived to be effective or ineffective. The present study’s aim was to identify and test the affective antecedents of perceived effectiveness of antidrug television messages in a sample of 190 adolescents in the 15–19 year age range. Factor-analytical tests of retrospective message evaluation items suggested two dimensions of perceived effectiveness, one that contained items such as convincingness whereas the other contained pleasantness items. Using retrospective data as well as real time valence and arousal ratings, we found that arousal underlies perceived convincingness and valence underlies perceived pleasantness. The results indicated activation of appetitive and defensive motivational systems, which suggests a clear motivational component to the concept of perceived message effectiveness. PMID:21499729

  17. Proline N-oxides: modulators of the 3D conformation of linear peptides through "NO-turns".

    PubMed

    Farahani, Majid D; Honarparvar, Bahareh; Albericio, Fernando; Maguire, Glenn E M; Govender, Thavendran; Arvidsson, Per I; Kruger, Hendrik G

    2014-07-07

    Small peptides are essential mediators of numerous physiological processes. Consequently, there is huge interest in the de novo design of peptides with a predictable folding and related biological activity. In this study, we investigate the possibility of modulating the secondary structure of tetrapeptides through proline N-oxide moieties and N-methylation of the peptide backbone. A series of tetrapeptides were synthesised to investigate the combined effect of Pro N-oxide and N-methylation of the amide bond on the (n + 1) residue in terms of cis- and trans-isomerization, as well as how these modifications direct potential intramolecular hydrogen bonding interactions. The right combination of both these parameters led to a trans to cis-conformational interconversion and a change in the nature of the hydrogen bonding interactions, as demonstrated by NMR spectroscopic, molecular modeling analysis and thermal coefficient studies. Proline N-oxide residues were proposed to induce turns we named as NO-γ-turns and NO-β-turns based on their similarity to traditional γ- and β-turns.

  18. Modified nondestructive colorimetric method to evaluate the variability of oxygen diffusion rate through wine bottle closures.

    PubMed

    Brotto, Laura; Battistutta, Franco; Tat, Lara; Comuzzo, Piergiorgio; Zironi, Roberto

    2010-03-24

    Some modifications to a previous nondestructive colorimetric method that permits evaluation of the oxygen diffusion rate through wine closures were proposed. The method is based on the reaction of indigo carmine solution with oxygen and the tristimulus measurement of the consequent color change. Simplified preparation and measurement procedures were set up, allowing the analysis of a large number of samples simultaneously. The method was applied to the evaluation of the variability within the lot of 20 different types of stoppers (synthetic, produced by molding, and natural cork). The closures were tested at a storage temperature of 26 degrees C. With regard to oxygen permeability, the natural cork stopper showed a low homogeneity within the lot, especially during the first month after bottling, whereas the synthetic closure showed a greater steadiness in the performance. The limits of the colorimetric method were also analyzed, and three possible causes of degradation of the indigo carmine solution were identified: oxygen, light, and heat.

  19. Analytical fuel property effects--small combustors

    NASA Technical Reports Server (NTRS)

    Sutton, R. D.; Troth, D. L.; Miles, G. A.

    1984-01-01

    The consequences of using broad-property fuels in both conventional and advanced state-of-the-art small gas turbine combustors are assessed. Eight combustor concepts were selected for initial screening, of these, four final combustor concepts were chosen for further detailed analysis. These included the dual orifice injector baseline combustor (a current production 250-C30 engine combustor) two baseline airblast injected modifications, short and piloted prechamber combustors, and an advanced airblast injected, variable geometry air staged combustor. Final predictions employed the use of the STAC-I computer code. This quasi 2-D model includes real fuel properties, effects of injector type on atomization, detailed droplet dynamics, and multistep chemical kinetics. In general, fuel property effects on various combustor concepts can be classified as chemical or physical in nature. Predictions indicate that fuel chemistry has a significant effect on flame radiation, liner wall temperature, and smoke emission. Fuel physical properties that govern atomization quality and evaporation rates are predicted to affect ignition and lean-blowout limits, combustion efficiency, unburned hydrocarbon, and carbon monoxide emissions.

  20. Implications of a frame dependent gravitational effective action for perturbations on the Robertson-Walker metric

    NASA Astrophysics Data System (ADS)

    Adler, Stephen L.

    In earlier work we showed that a frame dependent effective action motivated by the postulates of three-space general coordinate invariance and Weyl scaling invariance exactly mimics a cosmological constant in Robertson-Walker (RW) spacetimes. Here we study the implications of this effective action for small fluctuations around a spatially flat RW background geometry. The equations for the conserving extension of the modified stress-energy tensor can be integrated in closed form, and involve only the metric perturbation h00. Hence the equations for tensor and vector perturbations are unmodified, but there are Hubble scale additions to the scalar perturbation equations, which nonetheless admit no propagating wave solutions. Consequently, there are no modifications to standard gravitational wave propagation theory, but there may be observable implications for cosmology. We give a self-contained discussion, including an analysis of the restricted class of gauge transformations that act when a frame dependent effective action is present.

  1. Prevalence of L. Monocytogenes in Environmental Samples Collected in Dairy Plants of Sassari Province, Italy

    PubMed Central

    Fadda, Antonio; Frongia, Giorgio; Sanna, Antonietta; Melillo, Rita

    2015-01-01

    Listeria (L.) monocytogenes is frequently isolated from food production environment and often persists in dairy plants despite vigorous sanitation regimes. In recent years several alert notifications were sent to Rapid Alert System for Food Products system as a consequence of Listeria monocytogenes contamination of ricotta cheese. After the alert of 2012, competent authority (Local Health Unit of Sassari Province) organised an environmental monitoring plan with the partnership of the Institute for Experimental Veterinary Medicine of Sardinia to verify analysis of dairy plants own-check according to Regulation (EC) N° 2073/05 and further modifications. In 2014 n. 665 processing areas samples of n. 50 dairy plants of Sassari Province were examined. UNI EN ISO 11290-1:2005 for detection of L. monocytogenes was used. Non-compliance in n. 5 diary plants are observed (n. 8 positive samples). Post-non-compliance environmental sanitisation was efficient and own-check plans included appropriate corrective actions. PMID:27800407

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

    Abdel-Baki, K.; Boitier, F.; Diab, H.

    Due to their high potentiality for photovoltaic applications or coherent light sources, a renewed interest in hybrid organic perovskites has emerged for few years. When they are arranged in two dimensions, these materials can be considered as hybrid quantum wells. One consequence of the unique structure of 2D hybrid organic perovskites is a huge exciton binding energy that can be tailored through chemical engineering. We present experimental investigations of the exciton non-linearities by means of femtosecond pump-probe spectroscopy. The exciton dynamics is fitted with a bi-exponential decay with a free exciton life-time of ∼100 ps. Moreover, an ultrafast intraband relaxation (<150 fs)more » is also reported. Finally, the transient modification of the excitonic line is analyzed through the moment analysis and described in terms of reduction of the oscillator strength and linewidth broadening. We show that excitonic non-linearities in 2D hybrid organic perovskites share some behaviours of inorganic semiconductors despite their high exciton binding energy.« less

  3. Threshold corrections to the bottom quark mass revisited

    DOE PAGES

    Anandakrishnan, Archana; Bryant, B. Charles; Raby, Stuart

    2015-05-19

    Threshold corrections to the bottom quark mass are often estimated under the approximation that tan β enhanced contributions are the most dominant. In this work we revisit this common approximation made to the estimation of the supersymmetric thresh-old corrections to the bottom quark mass. We calculate the full one-loop supersymmetric corrections to the bottom quark mass and survey a large part of the phenomenological MSSM parameter space to study the validity of considering only the tan β enhanced corrections. Our analysis demonstrates that this approximation underestimates the size of the threshold corrections by ~12.5% for most of the considered parametermore » space. We discuss the consequences for fitting the bottom quark mass and for the effective couplings to Higgses. Here, we find that it is important to consider the additional contributions when fitting the bottom quark mass but the modifications to the effective Higgs couplings are typically O(few)% for the majority of the parameter space considered.« less

  4. Pitfalls and Precautions When Using Predicted Failure Data for Quantitative Analysis of Safety Risk for Human Rated Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Hatfield, Glen S.; Hark, Frank; Stott, James

    2016-01-01

    Launch vehicle reliability analysis is largely dependent upon using predicted failure rates from data sources such as MIL-HDBK-217F. Reliability prediction methodologies based on component data do not take into account risks attributable to manufacturing, assembly, and process controls. These sources often dominate component level reliability or risk of failure probability. While consequences of failure is often understood in assessing risk, using predicted values in a risk model to estimate the probability of occurrence will likely underestimate the risk. Managers and decision makers often use the probability of occurrence in determining whether to accept the risk or require a design modification. Due to the absence of system level test and operational data inherent in aerospace applications, the actual risk threshold for acceptance may not be appropriately characterized for decision making purposes. This paper will establish a method and approach to identify the pitfalls and precautions of accepting risk based solely upon predicted failure data. This approach will provide a set of guidelines that may be useful to arrive at a more realistic quantification of risk prior to acceptance by a program.

  5. Some problems associated with the analysis and interpretation of mixed carbonate and quartz beach sands, illustrated by examples from North-West Ireland

    NASA Astrophysics Data System (ADS)

    Carter, R. W. G.

    1982-09-01

    Mixes of carbonate and quartz sands, which are commonly encountered in Recent coastal sediments, require careful analysis if they are to be correctly interpreted. Grain-size data fall into multimodal or segmented zig-zag distributions which may require some kind of component separation if they are to be summarised by conventional statistics, and before they can be assigned to a particular hydrodynamic depositional process or environment. Unfortunately, separation techniques are only spasmodically applied, usually without due regard to the consequences. Such artificially filtered or truncated distributions are of little subsequent use. Using a range of samples from two beaches in NW Ireland, where carbonate proportions range from nearly zero to over sixty percent, the interrelationships of the two dominant components were examined. Where only a small carbonate proportion is incorporated into a large quartz one, predictable modifications of the size-curve are apparent. However, the components are more independent if mixtures are near equal. The occurrence of a number of distinctive combinations of simple straight lines and complex zig-zag curves probably reflects the relatively dynamic nature of the carbonate fraction.

  6. Broadband Noise Prediction When Turbulence Simulation Is Available - Derivation of Formulation 2B and Its Statistical Analysis

    NASA Technical Reports Server (NTRS)

    Farassat, Fereidoun; Casper, Jay H.

    2012-01-01

    We show that a simple modification of Formulation 1 of Farassat results in a new analytic expression that is highly suitable for broadband noise prediction when extensive turbulence simulation is available. This result satisfies all the stringent requirements, such as permitting the use of the exact geometry and kinematics of the moving body, that we have set as our goal in the derivation of useful acoustic formulas for the prediction of rotating blade and airframe noise. We also derive a simple analytic expression for the autocorrelation of the acoustic pressure that is valid in the near and far fields. Our analysis is based on the time integral of the acoustic pressure that can easily be obtained at any resolution for any observer time interval and digitally analyzed for broadband noise prediction. We have named this result as Formulation 2B of Farassat. One significant consequence of Formulation 2B is the derivation of the acoustic velocity potential for the thickness and loading terms of the Ffowcs Williams-Hawkings (FW-H) equation. This will greatly enhance the usefulness of the Fast Scattering Code (FSC) by providing a high fidelity boundary condition input for scattering predictions.

  7. Surfactant adsorption and aggregate structure of silica nanoparticles: a versatile stratagem for the regulation of particle size and surface modification

    NASA Astrophysics Data System (ADS)

    Chaudhary, Savita; Rohilla, Deepak; Mehta, S. K.

    2014-03-01

    The area of silica nanoparticles is incredibly polygonal. Silica particles have aroused exceptional deliberation in bio-analysis due to great progress in particular arenas, for instance, biocompatibility, unique properties of modifiable pore size and organization, huge facade areas and pore volumes, manageable morphology and amendable surfaces, elevated chemical and thermal stability. Currently, silica nanoparticles participate in crucial utilities in daily trade rationales such as power storage, chemical and genetic sensors, groceries dispensation and catalysis. Herein, the size-dependent interfacial relation of anionic silica nanoparticles with twelve altered categories of cationic surfactants has been carried out in terms of the physical chemical facets of colloid and interface science. The current analysis endeavours to investigate the virtual consequences of different surfactants through the development of the objective composite materials. The nanoparticle size controls, the surface-to-volume ratio and surface bend relating to its interaction with surfactant will also be addressed in this work. More importantly, the simulated stratagem developed in this work can be lengthened to formulate core-shell nanostructures with functional nanoparticles encapsulated in silica particles, making this approach valuable and extensively pertinent for employing sophisticated materials for catalysis and drug delivery.

  8. Evolution of SUMO Function and Chain Formation in Insects.

    PubMed

    Ureña, Enric; Pirone, Lucia; Chafino, Silvia; Pérez, Coralia; Sutherland, James D; Lang, Valérie; Rodriguez, Manuel S; Lopitz-Otsoa, Fernando; Blanco, Francisco J; Barrio, Rosa; Martín, David

    2016-02-01

    SUMOylation, the covalent binding of Small Ubiquitin-like Modifier (SUMO) to target proteins, is a posttranslational modification that regulates critical cellular processes in eukaryotes. In insects, SUMOylation has been studied in holometabolous species, particularly in the dipteran Drosophila melanogaster, which contains a single SUMO gene (smt3). This has led to the assumption that insects contain a single SUMO gene. However, the analysis of insect genomes shows that basal insects contain two SUMO genes, orthologous to vertebrate SUMO1 and SUMO2/3. Our phylogenetical analysis reveals that the SUMO gene has been duplicated giving rise to SUMO1 and SUMO2/3 families early in Metazoan evolution, and that later in insect evolution the SUMO1 gene has been lost after the Hymenoptera divergence. To explore the consequences of this loss, we have examined the characteristics and different biological functions of the two SUMO genes (SUMO1 and SUMO3) in the hemimetabolous cockroach Blattella germanica and compared them with those of Drosophila Smt3. Here, we show that the metamorphic role of the SUMO genes is evolutionary conserved in insects, although there has been a regulatory switch from SUMO1 in basal insects to SUMO3 in more derived ones. We also show that, unlike vertebrates, insect SUMO3 proteins cannot form polySUMO chains due to the loss of critical lysine residues within the N-terminal part of the protein. Furthermore, the formation of polySUMO chains by expression of ectopic human SUMO3 has a deleterious effect in Drosophila. These findings contribute to the understanding of the functional consequences of the evolution of SUMO genes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Analysis of biodegradation performance of furfural and 5-hydroxymethylfurfural by Amorphotheca resinae ZN1

    PubMed Central

    2014-01-01

    Background Furfural and 5-hydroxymethylfurfural (HMF) are the degradation products of lignocellulose during pretreatment operations and significantly inhibit the consequent enzymatic hydrolysis and fermentation processes. The biodetoxification fungus Amorphotheca resinae ZN1 had demonstrated its excellent capacity on degrading lignocellulose derived inhibitors and helped the fermentation processes to achieve high yield of ethanol and biochemicals. Analysis of the biological degradation performance of furfural and HMF by A. resinae ZN1 will provide essential information for their fast and complete removal from the pretreated lignocellulose materials and facilitate the consequent ethanol fermentation. Results The degradation performance of furfural and HMF by A. resinae ZN1 was investigated by capturing intermediate metabolic products at various culture conditions. A. resinae ZN1 converts furfural/HMF into furfuryl/HMF alcohols and furoic/HMF acids simultaneously at aerobic condition, and only the corresponding furfuryl/HMF alcohols are obtained at anaerobic condition. The existence of glucose accelerates the degradation rate of furfural and HMF by A. resinae ZN1 and the cell mass growth rate aerobically. Remarkably, glucose is not consumed before furfural or HMF is degraded to a low threshold concentration. The finding suggests that furfural or HMF has a substrate priority of utilization by A. resinae ZN1 than glucose. This property may help the detoxification of furfural and HMF to be operated without consuming glucose. Conclusions The biological degradation performance of furfural and HMF by A. resinae ZN1 was investigated experimentally. Oxygen supply is important on the complete biodegradation of furfural and HMF by A. resinae ZN1. Furfural or HMF has the priority of substrate utilization than glucose by A. resinae ZN1. This study provided important information for detoxification enhancement and strain modification. PMID:24708699

  10. Engineering of a Histone-Recognition Domain in Dnmt3a Alters the Epigenetic Landscape and Phenotypic Features of Mouse ESCs.

    PubMed

    Noh, Kyung-Min; Wang, Haibo; Kim, Hyunjae R; Wenderski, Wendy; Fang, Fang; Li, Charles H; Dewell, Scott; Hughes, Stephen H; Melnick, Ari M; Patel, Dinshaw J; Li, Haitao; Allis, C David

    2015-07-02

    Histone modification and DNA methylation are associated with varying epigenetic "landscapes," but detailed mechanistic and functional links between the two remain unclear. Using the ATRX-DNMT3-DNMT3L (ADD) domain of the DNA methyltransferase Dnmt3a as a paradigm, we apply protein engineering to dissect the molecular interactions underlying the recruitment of this enzyme to specific regions of chromatin in mouse embryonic stem cells (ESCs). By rendering the ADD domain insensitive to histone modification, specifically H3K4 methylation or H3T3 phosphorylation, we demonstrate the consequence of dysregulated Dnmt3a binding and activity. Targeting of a Dnmt3a mutant to H3K4me3 promoters decreases gene expression in a subset of developmental genes and alters ESC differentiation, whereas aberrant binding of another mutant to H3T3ph during mitosis promotes chromosome instability. Our studies support the general view that histone modification "reading" and DNA methylation are closely coupled in mammalian cells, and suggest an avenue for the functional assessment of chromatin-associated proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Spatially selective Au nanoparticle growth in laser-quality glass controlled by UV-induced phosphate-chain cross-linkage

    NASA Astrophysics Data System (ADS)

    Sigaev, Vladimir N.; Savinkov, Vitaly I.; Lotarev, Sergey V.; Shakhgildyan, Georgiy Yu; Lorenzi, Roberto; Paleari, Alberto

    2013-06-01

    Herein we describe how UV excitation of localized electronic states in phosphate glasses can activate structural rearrangements that influence the kinetics of Au nanoparticle (NP) thermal growth in Au-doped glass. The results suggest a novel strategy to address the problem of controlling nano-assembly processes of metal NP patterns in fully inorganic and chemically stable hard materials, such as laser-quality glasses. We show that the mechanism is promoted by opening and subsequent cross-linkage of phosphate chains under UV excitation of non-bridging groups in the amorphous network of the glass, with a consequent modification of Au diffusion and metal NP growth. Importantly, the micro-Raman mapping of the UV-induced modifications demonstrates that the process is restricted within the beam waist region of the focused UV laser beam. This fact is consistent with the need for more than one excitation event, close in time and in space, in order to promote structural cross-linkage and Au diffusion confinement. The stability of the photo-induced modifications makes it possible to design new metal patterning approaches for the fabrication of three-dimensional metal structures in laser-quality materials for high-power nonlinear applications.

  12. Spatially selective Au nanoparticle growth in laser-quality glass controlled by UV-induced phosphate-chain cross-linkage.

    PubMed

    Sigaev, Vladimir N; Savinkov, Vitaly I; Lotarev, Sergey V; Shakhgildyan, Georgiy Yu; Lorenzi, Roberto; Paleari, Alberto

    2013-06-07

    Herein we describe how UV excitation of localized electronic states in phosphate glasses can activate structural rearrangements that influence the kinetics of Au nanoparticle (NP) thermal growth in Au-doped glass. The results suggest a novel strategy to address the problem of controlling nano-assembly processes of metal NP patterns in fully inorganic and chemically stable hard materials, such as laser-quality glasses. We show that the mechanism is promoted by opening and subsequent cross-linkage of phosphate chains under UV excitation of non-bridging groups in the amorphous network of the glass, with a consequent modification of Au diffusion and metal NP growth. Importantly, the micro-Raman mapping of the UV-induced modifications demonstrates that the process is restricted within the beam waist region of the focused UV laser beam. This fact is consistent with the need for more than one excitation event, close in time and in space, in order to promote structural cross-linkage and Au diffusion confinement. The stability of the photo-induced modifications makes it possible to design new metal patterning approaches for the fabrication of three-dimensional metal structures in laser-quality materials for high-power nonlinear applications.

  13. Effect of thermal modification on rheological properties of polyethylene blends

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

    Siriprumpoonthum, Monchai; Nobukawa, Shogo; Yamaguchi, Masayuki, E-mail: m-yama@jaist.ac.jp

    2014-03-15

    We examined the effects of thermal modification under flow field on the rheological properties of linear low-density polyethylene (LLDPE) with high molecular weight, low-density polyethylene (LDPE), and their blends, without thermal stabilizer. Although structural changes during processing are not detected by size extrusion chromatography or nuclear magnetic resonance spectroscopy, linear viscoelastic properties changed greatly, especially for the LLDPE. A cross-linking reaction took place, leading to, presumably, star-shaped long-chain branches. Consequently, the modified LLDPE, having high zero-shear viscosity, became a thermorheologically complex melt. Moreover, it should be noted that the drawdown force, defined as the uniaxial elongational force at a constantmore » draw ratio, was significantly enhanced for the blends. Enhancement of elongational viscosity was also detected. The drawdown force and elongational viscosity are marked for the thermally modified blend as compared with those for the blend of thermally modified pure components. Intermolecular cross-linking reactions between LDPE and LLDPE, yielding polymers with more than two branch points per chain, result in marked strain-hardening in the elongational viscosity behavior even at small strain. The recovery curve of the oscillatory modulus after the shear modification is further evidence of a branched structure.« less

  14. Oxidative Post-Translational Modifications of an Amyloidogenic Immunoglobulin Light Chain Protein.

    PubMed

    Lu, Yanyan; Jiang, Yan; Prokaeva, Tatiana; Connors, Lawreen H; Costello, Catherine E

    2017-05-01

    Immunoglobulin light chain amyloidosis (AL) is a plasma cell disorder characterized by overproduction and deposition of monoclonal immunoglobulin (Ig) light chains (LC) or variable region fragments as amyloid fibrils in various organs and tissues. Much clinical evidence indicates that patients with AL amyloidosis sustain cardiomyocyte impairment and suffer from oxidative stress. We seek to understand the underlying biochemical pathways whose disruption or amplification during sporadic or sustained disease states leads to harmful physiological consequences and to determine the detailed structures of intermediates and products that serve as signposts for the biochemical changes and represent potential biomarkers. In this study, matrix-assisted laser desorption/ionization mass spectrometry provided extensive evidence for oxidative post-translational modifications (PTMs) of an amyloidogenic Ig LC protein from a patient with AL amyloidosis. Some of the tyrosine residues were heavily mono- or di-chlorinated. In addition, a novel oxidative conversion to a nitrile moiety was observed for many of the terminal aminomethyl groups on lysine side chains. In vitro experiments using model peptides, in-solution oxidation, and click chemistry demonstrated that hypochlorous acid produced by the myeloperoxidase - hydrogen peroxide - chloride system could be responsible for these and other, more commonly observed modifications.

  15. Microbial Inhibition of Fusarium Pathogens and Biological Modification of Trichothecenes in Cereal Grains

    PubMed Central

    Wachowska, Urszula; Packa, Danuta

    2017-01-01

    Fungi of the genus Fusarium infect cereal crops during the growing season and cause head blight and other diseases. Their toxic secondary metabolites (mycotoxins) contaminate grains. Several dozen toxic compounds produced by fungal pathogens have been identified to date. Type B trichothecenes—deoxynivalenol, its acetyl derivatives and nivalenol (produced mainly by F. graminearum and F. culmorum)—are most commonly detected in cereal grains. “T-2 toxin” (produced by, among others, F. sporotrichioides) belongs to type-A trichothecenes which are more toxic than other trichothecenes. Antagonistic bacteria and fungi can affect pathogens of the genus Fusarium via different modes of action: direct (mycoparasitism or hyperparasitism), mixed-path (antibiotic secretion, production of lytic enzymes) and indirect (induction of host defense responses). Microbial modification of trichothecenes involves acetylation, deacetylation, oxidation, de-epoxidation, and epimerization, and it lowers the pathogenic potential of fungi of the genus Fusarium. Other modifing mechanisms described in the paper involve the physical adsorption of mycotoxins in bacterial cells and the conjugation of mycotoxins to glucose and other compounds in plant and fungal cells. The development of several patents supports the commercialization and wider application of microorganisms biodegrading mycotoxins in grains and, consequently, in feed additives. PMID:29261142

  16. Recent Advances in Attention Bias Modification for Substance Addictions

    PubMed Central

    Zhang, Melvyn Weibin; Ying, Jiang Bo; Song, Guo; Fung, Daniel S. S.; Smith, Helen E.

    2018-01-01

    Research on attentional bias modification has increased since 2014. A recent meta-analysis demonstrates evidence for bias modification for substance disorders, including alcohol and tobacco use disorders. Several pharmacological trials have shown that pharmacological agents can attenuate and modify such attentional bias. The pharmacological trials that have appeared to date have produced mixed results, which has clinical implications. Developments in Internet and mobile technologies have transformed how attention bias modification is currently being achieved. There remains great potential for further research that examines the efficacy of technology-aided attention bias interventions. PMID:29617325

  17. ChIP-Seq Analysis for Identifying Genome-Wide Histone Modifications Associated with Stress-Responsive Genes in Plants.

    PubMed

    Li, Guosheng; Jagadeeswaran, Guru; Mort, Andrew; Sunkar, Ramanjulu

    2017-01-01

    Histone modifications represent the crux of epigenetic gene regulation essential for most biological processes including abiotic stress responses in plants. Thus, identification of histone modifications at the genome-scale can provide clues for how some genes are 'turned-on' while some others are "turned-off" in response to stress. This chapter details a step-by-step protocol for identifying genome-wide histone modifications associated with stress-responsive gene regulation using chromatin immunoprecipitation (ChIP) followed by sequencing of the DNA (ChIP-seq).

  18. Optimal Control Modification for Robust Adaptation of Singularly Perturbed Systems with Slow Actuators

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan T.; Ishihara, Abraham; Stepanyan, Vahram; Boskovic, Jovan

    2009-01-01

    Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. The model matching conditions in the transformed time coordinate results in increase in the feedback gain and modification of the adaptive law.

  19. Surface modification effects on defect-related photoluminescence in colloidal CdS quantum dots.

    PubMed

    Lee, TaeGi; Shimura, Kunio; Kim, DaeGwi

    2018-05-03

    We investigated the effects of surface modification on the defect-related photoluminescence (PL) band in colloidal CdS quantum dots (QDs). A size-selective photoetching process and a surface modification technique with a Cd(OH)2 layer enabled the preparation of size-controlled CdS QDs with high PL efficiency. The Stokes shift of the defect-related PL band before and after the surface modification was ∼1.0 eV and ∼0.63 eV, respectively. This difference in the Stokes shifts suggests that the origin of the defect-related PL band was changed by the surface modification. Analysis by X-ray photoelectron spectroscopy revealed that the surface of the CdS QDs before and after the surface modification was S rich and Cd rich, respectively. These results suggest that Cd-vacancy acceptors and S-vacancy donors affect PL processes in CdS QDs before and after the surface modification, respectively.

  20. Modification of wheat starch with succinic acid/acetanhydride and azelaic acid/acetanhydride mixtures. II. Chemical and physical properties.

    PubMed

    Ačkar, Durđica; Subarić, Drago; Babić, Jurislav; Miličević, Borislav; Jozinović, Antun

    2014-08-01

    The aim of this research was to investigate the influence of modification with succinic acid/acetanhydride and azelaic acid/acetanhydride mixtures on chemical and physical properties of wheat starch. Starch was isolated from two wheat varieties and modified with mixtures of succinic acid and acetanhydride and azelaic acid and acetanhydride in 4, 6 and 8% (w/w). Total starch content, resistant starch content, degree of modification, changes in FT-IR spectra, colour, gel texture and freeze-thaw stability were determined. Results showed that resistant starch content increased by both investigated modifications, and degree of modification increased proportionally to amount of reagents used. FT-IR analysis of modified starches showed peak around 1,740 cm(-1), characteristic for carbonyl group of ester. Total colour difference caused by modifications was detectable by trained people. Adhesiveness significantly increased, while freeze-thaw stability decreased by both investigated modifications.

  1. Niche construction initiates the evolution of mutualistic interactions.

    PubMed

    Buser, Claudia C; Newcomb, Richard D; Gaskett, Anne C; Goddard, Matthew R

    2014-10-01

    Niche construction theory explains how organisms' niche modifications may feed back to affect their evolutionary trajectories. In theory, the evolution of other species accessing the same modified niche may also be affected. We propose that this niche construction may be a general mechanism driving the evolution of mutualisms. Drosophilid flies benefit from accessing yeast-infested fruits, but the consequences of this interaction for yeasts are unknown. We reveal high levels of variation among strains of Saccharomyces cerevisiae in their ability to modify fruits and attract Drosophila simulans. More attractive yeasts are dispersed more frequently, both in the lab and in the field, and flies associated with more attractive yeasts have higher fecundity. Although there may be multiple natural yeast and fly species interactions, our controlled assays in the lab and field provide evidence of a mutualistic interaction, facilitated by the yeast's niche modification. © 2014 John Wiley & Sons Ltd/CNRS.

  2. Monitoring of tissue modification with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Luo, Qingming; Yao, Lei; Cheng, Haiying; Zeng, Shaoqun

    2002-04-01

    An experimental monitoring of tissue modification of in vitro and in vivo rabbit dura mater with administration of osmotical agents, 40% glucose solution and glycerol, using optical coherence tomography was presented. The preliminary results of experimental study of influence of osmotical liquids (glucose solutions, glycerol) of rabbit dura mater were reported. The significant decreasing of the light from surface and increasing of the light from the deep of dura mater under action of osmotical solutions and the increasing of OCT imaging depth were demonstrated. Experiments showed that administration of osmolytes to dura mater allowed for effective and temporary control of its optical characteristics, which made dura mater more transparent, increased the ability of light penetrating the tissue, and consequently improved the optical imaging depth. It is a significant study, which can improve penetration of optical imaging of cerebral function and acquire more information of the deep brain tissue.

  3. Lifestyle, pregnancy and epigenetic effects.

    PubMed

    Barua, Subit; Junaid, Mohammed A

    2015-01-01

    Rapidly growing evidences link maternal lifestyle and prenatal factors with serious health consequences and diseases later in life. Extensive epidemiological studies have identified a number of factors such as diet, stress, gestational diabetes, exposure to tobacco and alcohol during gestation as influencing normal fetal development. In light of recent discoveries, epigenetic mechanisms such as alteration of DNA methylation, chromatin modifications and modulation of gene expression during gestation are believed to possibly account for various types of plasticity such as neural tube defects, autism spectrum disorder, congenital heart defects, oral clefts, allergies and cancer. The purpose of this article is to review a number of published studies to fill the gap in our understanding of how maternal lifestyle and intrauterine environment influence molecular modifications in the offspring, with an emphasis on epigenetic alterations. To support these associations, we highlighted laboratory studies of rodents and epidemiological studies of human based on sampling population cohorts.

  4. Interplay between social experiences and the genome: epigenetic consequences for behavior.

    PubMed

    Champagne, Frances A

    2012-01-01

    Social experiences can have a persistent effect on biological processes leading to phenotypic diversity. Variation in gene regulation has emerged as a mechanism through which the interplay between DNA and environments leads to the biological encoding of these experiences. Epigenetic modifications-molecular pathways through which transcription is altered without altering the underlying DNA sequence-play a critical role in the normal process of development and are being increasingly explored as a mechanism linking environmental experiences to long-term biobehavioral outcomes. In this review, evidence implicating epigenetic factors, such as DNA methylation and histone modifications, in the link between social experiences occurring during the postnatal period and in adulthood and altered neuroendocrine and behavioral outcomes will be highlighted. In addition, the role of epigenetic mechanisms in shaping variation in social behavior and the implications of epigenetics for our understanding of the transmission of traits across generations will be discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Carbonylation of milk powder proteins as a consequence of processing conditions.

    PubMed

    Fenaille, François; Parisod, Véronique; Tabet, Jean-Claude; Guy, Philippe A

    2005-08-01

    During industrial treatments, milk proteins could be oxidatively modified, thus leading to the formation of modified/oxidised amino acid residues. The apparition of such modified residues may contribute to the formation of new immunologically reactive structures. Some of these adducts could, in an advanced stage, lead to cross-linked protein species whose proteolytic susceptibility would be drastically decreased. Such protein species, that are resistant to digestion, could also constitute major food allergens. Therefore, these oxidative protein modifications tend to increase the natural allergenicity of milk proteins. For these reasons, monitoring milk protein oxidative modifications could be very useful regarding both product quality and allergenicity issues. In the present paper, we highlight, using different analytical approaches, the preferential carbonylation of beta-lactoglobulin (beta-Lg) during industrial treatments of milk. This result is particularly interesting since native beta-Lg represents one of the major milk allergens.

  6. Adaptation of human adipose tissue to hypocaloric diet.

    PubMed

    Rossmeislová, L; Mališová, L; Kračmerová, J; Štich, V

    2013-05-01

    Hypocaloric diet is a key component of the weight-reducing treatment of obesity and obesity-related disorders. Hypocaloric diets and the associated weight reduction promote improvement of metabolic profile of obese individuals. Among the mechanisms that underlie this beneficial metabolic outcome, the diet-induced modifications of morphological and functional characteristics of human adipose tissue (AT) are believed to have an important role. Prospective studies of hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte metabolism, namely lipolysis and lipogenesis, and associated changes of the adipocyte size. The endocrine function of AT, which involves cytokine and adipokine production by adipocytes, as well as by cells of stromavascular fraction, is also regulated by dietary intervention. Related inflammatory status of AT is modulated also as a consequence of the changes in recruitment of immune cells, mainly macrophages, in AT. Here, we give an overview of metabolic and endocrine modifications in human AT induced by a variety of hypocaloric diets.

  7. Band structure modification of the thermoelectric Heusler-phase TiFe2Sn via Mn substitution.

    PubMed

    Zou, Tianhua; Jia, Tiantian; Xie, Wenjie; Zhang, Yongsheng; Widenmeyer, Marc; Xiao, Xingxing; Weidenkaff, Anke

    2017-07-19

    Doping (or substitution)-induced modification of the electronic structure to increase the electronic density of states (eDOS) near the Fermi level is considered as an effective strategy to enhance the Seebeck coefficient, and may consequently boost the thermoelectric performance. Through density-functional theory calculations of Mn-substituted TiFe 2-x Mn x Sn compounds, we demonstrate that the d-states of the substituted Mn atoms induce a strong resonant level near the Fermi energy. Our experimental results are in good agreement with the calculations. They show that Mn substitution results in a large increase of the Seebeck coefficient, arising from an enhanced eDOS in Heusler compounds. The results prove that a proper substitution position and element selection can increase the eDOS, leading to a higher Seebeck coefficient and thermoelectric performance of ecofriendly materials.

  8. Progressing From Initially Ambiguous Functional Analyses: Three Case Examples

    PubMed Central

    Tiger, Jeffrey H.; Fisher, Wayne W.; Toussaint, Karen A.; Kodak, Tiffany

    2009-01-01

    Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments. PMID:19233611

  9. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle.

    PubMed

    Malkus, Kristen A; Tsika, Elpida; Ischiropoulos, Harry

    2009-06-05

    While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD) as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis.

  10. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle

    PubMed Central

    Malkus, Kristen A; Tsika, Elpida; Ischiropoulos, Harry

    2009-01-01

    While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD) as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis. PMID:19500376

  11. Modification of enzymes by use of high-pressure homogenization.

    PubMed

    Dos Santos Aguilar, Jessika Gonçalves; Cristianini, Marcelo; Sato, Helia Harumi

    2018-07-01

    High-pressure is an emerging and relatively new technology that can modify various molecules. High-pressure homogenization (HPH) has been used in several studies on protein modification, especially in enzymes used or found in food, from animal, plant or microbial resources. According to the literature, the enzymatic activity can be modulated under pressure causing inactivation, stabilization or activation of the enzymes, which, depending on the point of view could be very useful. Homogenization can generate changes in the structure of the enzyme modifying various chemical bonds (mainly weak bonds) causing different denaturation levels and, consequently, affecting the catalytic activity. This review aims to describe the various alterations due to HPH treatment in enzymes, to show the influence of high-pressure on proteins and to report the HPH effects on the enzymatic activity of different enzymes employed in the food industry and research. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Modification of β-Sheet Forming Peptide Hydrophobic Face: Effect on Self-Assembly and Gelation

    PubMed Central

    2016-01-01

    β-Sheet forming peptides have attracted significant interest for the design of hydrogels for biomedical applications. One of the main challenges is the control and understanding of the correlations between peptide molecular structure, the morphology, and topology of the fiber and network formed as well as the macroscopic properties of the hydrogel obtained. In this work, we have investigated the effect that functionalizing these peptides through their hydrophobic face has on their self-assembly and gelation. Our results show that the modification of the hydrophobic face results in a partial loss of the extended β-sheet conformation of the peptide and a significant change in fiber morphology from straight to kinked. As a consequence, the ability of these fibers to associate along their length and form large bundles is reduced. These structural changes (fiber structure and network topology) significantly affect the mechanical properties of the hydrogels (shear modulus and elasticity). PMID:27089379

  13. Cell Signalling Through Covalent Modification and Allostery

    NASA Astrophysics Data System (ADS)

    Johnson, Louise N.

    Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases catalyze the transfer of the γ-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. This covalent modification allows activation or inhibition of enzyme activity, creates recognition sites for other proteins and promotes order/disorder or disorder/order transitions. These properties regulate ­signalling pathways and cellular processes that mediate metabolism, transcription, cell cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. In this lecture I shall review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase and the cell cycle cyclin dependent protein kinases as illustrations. Regulation of protein phosphorylation may be disrupted in the diseased state and protein kinases have become high profile targets for drug development. To date there are 11 compounds that have been approved for clinical use in the treatment of cancer.

  14. Methodological guidelines for developing accident modification functions.

    PubMed

    Elvik, Rune

    2015-07-01

    This paper proposes methodological guidelines for developing accident modification functions. An accident modification function is a mathematical function describing systematic variation in the effects of road safety measures. The paper describes ten guidelines. An example is given of how to use the guidelines. The importance of exploratory analysis and an iterative approach in developing accident modification functions is stressed. The example shows that strict compliance with all the guidelines may be difficult, but represents a level of stringency that should be strived for. Currently the main limitations in developing accident modification functions are the small number of good evaluation studies and the often huge variation in estimates of effect. It is therefore still not possible to develop accident modification functions for very many road safety measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Aircraft modifications: Assessing the current state of Air Force aircraft modifications and the implications for future military capability

    NASA Astrophysics Data System (ADS)

    Hill, Owen Jacob

    How prepared is the U.S. Air Force to modify its aircraft fleet in upcoming years? Aircraft modernization is a complex interaction of new and legacy aircraft, organizational structure, and planning policy. This research will take one component of modernization: aircraft modification, and apply a new method of analysis in order to help formulate policy to promote modernization. Departing from previous small-sample studies dependent upon weight as a chief explanatory variable, this dissertation incorporates a comprehensive dataset that was constructed for this research of all aircraft modifications from 1996 through 2005. With over 700 modification programs, this dataset is used to examine changes to the current modification policy using policy-response regression models. These changes include separating a codependent procurement and installation schedule, reducing the documentation requirements for safety modifications, and budgeting for aging aircraft modifications. The research then concludes with predictive models for the F-15 and F-16 along with their replacements: the F-22 and F-35 Joint Strike Fighter.

  16. Chemical methods for encoding and decoding of posttranslational modifications

    PubMed Central

    Chuh, Kelly N.; Batt, Anna R.; Pratt, Matthew R.

    2016-01-01

    A large array of posttranslational modifications can dramatically change the properties of proteins and influence different aspects of their biological function such as enzymatic activity, binding interactions, and proteostasis. Despite the significant knowledge that has been gained about the function of posttranslational modifications using traditional biological techniques, the analysis of the site-specific effects of a particular modification, the identification of the full compliment of modified proteins in the proteome, and the detection of new types of modifications remains challenging. Over the years, chemical methods have contributed significantly in both of these areas of research. This review highlights several posttranslational modifications where chemistry-based approaches have made significant contributions to our ability to both prepare homogeneously modified proteins and identify and characterize particular modifications in complex biological settings. As the number and chemical diversity of documented posttranslational modifications continues to rise, we believe that chemical strategies will be essential to advance the field in years to come. PMID:26933738

  17. 40 CFR 1400.7 - In general.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.7 In general. The Administrator shall provide OCA information to government officials as provided in this subpart. Any OCA...

  18. 40 CFR 1400.7 - In general.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.7 In general. The Administrator shall provide OCA information to government officials as provided in this subpart. Any OCA...

  19. 40 CFR 1400.7 - In general.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.7 In general. The Administrator shall provide OCA information to government officials as provided in this subpart. Any OCA...

  20. 40 CFR 1400.7 - In general.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.7 In general. The Administrator shall provide OCA information to government officials as provided in this subpart. Any OCA...

  1. Modification of working conditions based on ergo THK reducing workload, muscle tension, and fatigue of rice milling workers in J village

    NASA Astrophysics Data System (ADS)

    Ruliati, L. P.; Adiputra, N.; Sutjana, I. D. P.; Sutajaya, I. M.

    2017-11-01

    Rice mill is one of the businesses in informal sector. From the rice milling process, ergonomic problems arise when employees work with bent position that done repeatedly to lift grain sacks to be transferred to peeler machine. This situation will affect the comfort of work, thus increasing the workload, muscle tension, and fatigue. The consequence will certainly affect the health and productivity of workers. In this study introduces ergo Tri Hita Karana (ergo THK) as an ergonomics intervention model which solves ergonomics problems of the cultural aspects of THK. The study aim is to determine the modification of working conditions based Ergo THK to reduce workload, muscle tension and fatigue. This research uses Randomized Pretest and Posttest Control Group Design experimental design. The subjects were 30 male rice mill workers with an age range of 16 until 56 years, and then divided into 15 subjects in the control group and 15 subjects in the treatment group. The results showed that the average posttest workloads in the control group are 136.950 more less 0.297 and in the treatment group are 107.60 more less 0.396. Significance analysis showed that after the two groups done their activities, the average workload significantly different p less than 0.005. The amount of reduction in the workload between the two groups was 21.43 percent. In muscle tension posttest showed that the mean score of the muscle tension in the control group was 62.67 more less 7.31 and the treatment group was 20.96 more less 2.96. Significance analysis showed that both groups mean muscle-tension results were significantly different p less than 0.005. The amount of reduction in tension between the control group and the treatment group while working was 66.55 percent. At fatigue posttest showed that the mean score of fatigue in the control group was 76.40 more less 13.51 and the treatment group was 55.53 more less 9.51. Significant analysis showed that the mean fatigue of both groups significantly different p less than 0.005. The amount of reduction in fatigue between the control group and the treatment group while working was 27.31 percent. From this study it can be concluded that the modification of the working conditions based on Ergo THK can reduce the workload by 21.43 percent, muscle tension by 66.55 percent and fatigue by 27.31 percent.

  2. Natural and human-induced driving factors in the evolution of tidal channels: case studies in the Venice Lagoon (Italy).

    NASA Astrophysics Data System (ADS)

    Rizzetto, Federica

    2013-04-01

    Coastal wetlands are largely affected by a complex variety of both natural and anthropogenic factors, which induce evident, often irreversible, geomorphological transformations. In particular, this research focuses on the main processes that influence the evolution of tidal channels in salt marshes and shows the results derived from the analysis of some case studies in the Venice Lagoon (northwestern Adriatic Sea, Italy). Here tidal network has been recognized as significantly sensitive to sea-level rise and tide oscillations (Rizzetto and Tosi, 2011; Rizzetto and Tosi, 2012), but it is also vulnerable to human impact. The sites were selected in areas characterized by low anthropogenic pressure to prevent strong human interferences from completely masking the effects of natural forces. The interpretation of a large number of high-resolution aerial photographs, taken since the mid 1930s, allowed identifying in detail tidal channel evolution, both in the long- and in the short-term. The observation of historical and recent topographic maps completed the study and provided other important data to define the modifications occurred in the past two centuries. The channel planform changes were determined through the morphometric analysis of the tidal network, carried out using a Geographic Information System software. These modifications were interpreted in the light of sea-level oscillations (i.e. relative sea-level rise and strength/frequency of high tides, which are increasing owing to climate changes), variations of sediment supply, and human activities occurred in the past century. The joint analysis of all the data allowed distinguishing the changes induced by both relative sea-level rise and high tides on planform pattern and evolution of tidal channels, and identifying the effects of human interferences, which magnified the impact of natural factors (e.g. groundwater exploitation responsible for high subsidence rates between 1950 and 1970 and, consequently, for an increase of relative sea-level rise in the same period) and/or produced other hydrodynamic, morphological, sedimentological modifications in the salt marshes, often resulting in erosion. References Rizzetto F., Tosi L., 2011. Aptitude of modern salt marshes to counteract relative sea-level rise, Venice Lagoon (Italy). Geology, 39 (8), 755-758. doi: 10.1130/G31736.1. Rizzetto F., Tosi L., 2012. Rapid response of tidal channel networks to sea-level variations (Venice Lagoon, Italy). Global and Planetary Change, 92-93, 191-197, doi: 10.1016/j.gloplacha.2012.05.022.

  3. Maximum type 1 error rate inflation in multiarmed clinical trials with adaptive interim sample size modifications.

    PubMed

    Graf, Alexandra C; Bauer, Peter; Glimm, Ekkehard; Koenig, Franz

    2014-07-01

    Sample size modifications in the interim analyses of an adaptive design can inflate the type 1 error rate, if test statistics and critical boundaries are used in the final analysis as if no modification had been made. While this is already true for designs with an overall change of the sample size in a balanced treatment-control comparison, the inflation can be much larger if in addition a modification of allocation ratios is allowed as well. In this paper, we investigate adaptive designs with several treatment arms compared to a single common control group. Regarding modifications, we consider treatment arm selection as well as modifications of overall sample size and allocation ratios. The inflation is quantified for two approaches: a naive procedure that ignores not only all modifications, but also the multiplicity issue arising from the many-to-one comparison, and a Dunnett procedure that ignores modifications, but adjusts for the initially started multiple treatments. The maximum inflation of the type 1 error rate for such types of design can be calculated by searching for the "worst case" scenarios, that are sample size adaptation rules in the interim analysis that lead to the largest conditional type 1 error rate in any point of the sample space. To show the most extreme inflation, we initially assume unconstrained second stage sample size modifications leading to a large inflation of the type 1 error rate. Furthermore, we investigate the inflation when putting constraints on the second stage sample sizes. It turns out that, for example fixing the sample size of the control group, leads to designs controlling the type 1 error rate. © 2014 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Subsynchronous instability of a geared centrifugal compressor of overhung design

    NASA Technical Reports Server (NTRS)

    Hudson, J. H.; Wittman, L. J.

    1980-01-01

    The original design analysis and shop test data are presented for a three stage (poster) air compressor with impellers mounted on the extensions of a twin pinion gear, and driven by an 8000 hp synchronous motor. Also included are field test data, subsequent rotor dynamics analysis, modifications, and final rotor behavior. A subsynchronous instability existed on a geared, overhung rotor. State-of-the-art rotor dynamics analysis techniques provided a reasonable analytical model of the rotor. A bearing modification arrived at analytically eliminated the instability.

  5. Constraints on the Formation and Modification of Lobate Debris Aprons Through Categorized Crater Counts

    NASA Astrophysics Data System (ADS)

    Berman, D. C.; Crown, D. A.; Joseph, E. C. S.

    2012-03-01

    Compilation of crater counts using CTX images and analysis of SFD, coupled with categorization of crater morphologies, provides important insights into interpretation of the formation and modification of lobate debris aprons.

  6. Effect of mold designs on molten metal behaviour in high-pressure die casting

    NASA Astrophysics Data System (ADS)

    Ibrahim, M. D.; Rahman, M. R. A.; Khan, A. A.; Mohamad, M. R.; Suffian, M. S. Z. M.; Yunos, Y. S.; Wong, L. K.; Mohtar, M. Z.

    2017-04-01

    This paper presents a research study conducted in a local automotive component manufacturer that produces aluminium alloy steering housing local and global markets. This study is to investigate the effect of design modification of mold in die casting as to improve the production rate. Design modification is carried out on the casting shot of the mold. Computer flow simulation was carried out to study the flow of molten metal in the mold with respect to the mold design modification. The design parameters of injection speed, die temperature and clamping force has been included in the study. The result of the simulation showed that modifications of casting shot give significant impact towards the molten flow behaviour in casting process. The capabilities and limitations of die casting process simulation to conduct defect analysis had been optimized. This research will enhance the efficiency of the mass production of the industry of die casting with the understanding of defect analysis, which lies on the modification of the mold design, a way early in its stages of production.

  7. Morphology modification of gold nanoparticles from nanoshell to C-shape: Improved surface enhanced Raman scattering

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

    Xing, Ting-Yang; Zhu, Jian; Li, Jian-Jun

    Morphology modification of nanostructures is of great interest, because it can be used to fabricate nanostructures which are hard to be done using other methods. Different from traditional lithographic technique which is slow and expensive, morphology modification is easy, cheap, and reproducible. In this paper, modification of the optical and morphological properties of a hollow gold nanoshell (HGNS) is achieved by using H{sub 2}O{sub 2} as an oxidizer. The reshaping of these nanostructures has been demonstrated as a consequence of an oxidation process in which HGNSs are dissolved by H{sub 2}O{sub 2} under the acidic conditions provided by HCl. Wemore » investigate the oxidation process by a transmission electron microscope and propose a reshaping model involving four different shapes (HGNS, HGNS with hole, gold nanoring, and C-shaped gold nanoparticle) which are corresponding to the oxidation products of HGNSs at different pH values. Besides, the surface enhanced Raman scattering (SERS) activity of each oxidation product has been evaluated by using rhodamine 6G as the Raman active probe. It has been observed that the C-shaped gold nanoparticles which are corresponding to the oxidation products at the minimum pH value have the highest SERS activity and this result can also be interpreted by discrete-dipole approximation simulations. We demonstrate that the morphology modification of HGNSs becomes possible in a controlled manner using wet chemistry and can be used in preparation of gold nanoparticles such as HGNS with hole, gold nanoring, and C-shaped gold nanoparticle with large SERS activity. These nanostructures must have potential use in many plasmonic areas, including sensing, catalysis, and biomedicine.« less

  8. Effects of arsenic on modification of promyelocytic leukemia (PML): PML responds to low levels of arsenite

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

    Hirano, Seishiro, E-mail: seishiro@nies.go.jp; Graduate School of Pharmaceutical Sciences, Chiba University; Watanabe, Takayuki

    2013-12-15

    Inorganic arsenite (iAs{sup 3+}) is a two-edged sword. iAs{sup 3+} is a well-known human carcinogen; nevertheless, it has been used as a therapeutic drug for acute promyelocytic leukemia (APL), which is caused by a fusion protein comprising retinoic acid receptor-α and promyelocytic leukemia (PML). PML, a nuclear transcription factor, has a RING finger domain with densely positioned cysteine residues. To examine PML-modulated cellular responses to iAs{sup 3+}, CHO-K1 and HEK293 cells were each used to establish cell lines that expressed ectopic human PML. Overexpression of PML increased susceptibility to iAs{sup 3+} in CHO-K1 cells, but not in HEK293 cells. Exposuremore » of PML-transfected cells to iAs{sup 3+} caused PML to change from a soluble form to less soluble forms, and this modification of PML was observable even with just 0.1 μM iAs{sup 3+} (7.5 ppb). Western blot and immunofluorescent microscopic analyses revealed that the biochemical changes of PML were caused at least in part by conjugation with small ubiquitin-like modifier proteins (SUMOylation). A luciferase reporter gene was used to investigate whether modification of PML was caused by oxidative stress or activation of antioxidant response element (ARE) in CHO-K1 cells. Modification of PML protein occurred faster than activation of the ARE in response to iAs{sup 3+}, suggesting that PML was not modified as a consequence of oxidative stress-induced ARE activation. - Highlights: • PML was found in nuclear microspecles in response to arsenite. • Arsenite triggers SUMOylation of PML. • Arsenite modifies PML at as low as 0.1 μM. • Modification of PML is not caused by ARE activation.« less

  9. Modifying upper-limb inter-joint coordination in healthy subjects by training with a robotic exoskeleton.

    PubMed

    Proietti, Tommaso; Guigon, Emmanuel; Roby-Brami, Agnès; Jarrassé, Nathanaël

    2017-06-12

    The possibility to modify the usually pathological patterns of coordination of the upper-limb in stroke survivors remains a central issue and an open question for neurorehabilitation. Despite robot-led physical training could potentially improve the motor recovery of hemiparetic patients, most of the state-of-the-art studies addressing motor control learning, with artificial virtual force fields, only focused on the end-effector kinematic adaptation, by using planar devices. Clearly, an interesting aspect of studying 3D movements with a robotic exoskeleton, is the possibility to investigate the way the human central nervous system deals with the natural upper-limb redundancy for common activities like pointing or tracking tasks. We asked twenty healthy participants to perform 3D pointing or tracking tasks under the effect of inter-joint velocity dependant perturbing force fields, applied directly at the joint level by a 4-DOF robotic arm exoskeleton. These fields perturbed the human natural inter-joint coordination but did not constrain directly the end-effector movements and thus subjects capability to perform the tasks. As a consequence, while the participants focused on the achievement of the task, we unexplicitly modified their natural upper-limb coordination strategy. We studied the force fields direct effect on pointing movements towards 8 targets placed in the 3D peripersonal space, and we also considered potential generalizations on 4 distinct other targets. Post-effects were studied after the removal of the force fields (wash-out and follow up). These effects were quantified by a kinematic analysis of the pointing movements at both end-point and joint levels, and by a measure of the final postures. At the same time, we analysed the natural inter-joint coordination through PCA. During the exposition to the perturbative fields, we observed modifications of the subjects movement kinematics at every level (joints, end-effector, and inter-joint coordination). Adaptation was evidenced by a partial decrease of the movement deviations due to the fields, during the repetitions, but it occurred only on 21% of the motions. Nonetheless post-effects were observed in 86% of cases during the wash-out and follow up periods (right after the removal of the perturbation by the fields and after 30 minutes of being detached from the exoskeleton). Important inter-individual differences were observed but with small variability within subjects. In particular, a group of subjects showed an over-shoot with respect to the original unexposed trajectories (in 30% of cases), but the most frequent consequence (in 55% of cases) was the partial persistence of the modified upper-limb coordination, adopted at the time of the perturbation. Temporal and spatial generalizations were also evidenced by the deviation of the movement trajectories, both at the end-effector and at the intermediate joints and the modification of the final pointing postures towards targets which were never exposed to any field. Such results are the first quantified characterization of the effects of modification of the upper-limb coordination in healthy subjects, by imposing modification through viscous force fields distributed at the joint level, and could pave the way towards opportunities to rehabilitate pathological arm synergies with robots.

  10. Sr and U isotope ratios in soil waters as tracers of weathering dynamic in soils (Strengbach catchment - Vosges-mountains; France).

    NASA Astrophysics Data System (ADS)

    Chabaux, François; Prunier, Jonathan; Pierret, Marie-Claire; Stille, Peter

    2013-04-01

    It is proposed in this study to highlight the interest of multi-tracer geochemical approaches combining measurement of major and trace element concentrations along with U and Sr isotopic ratios to constrain the characterization of the present-day weathering processes controlling the chemical composition of waters and soils in natural ecosystems. This is important if we want to predict and to model correctly the response of ecosystems to recent environmental changes. The approach is applied to the small granitic Strengbah Catchment, located in the Vosges Mountain (France), used and equipped as a hydro-geochemical observatory since 1986 (Observatoire Hydro-Géochimique de l'Environnement; http://ohge.u-strasbg.fr). This study includes the analysis of major and trace element concentrations and (U-Sr) isotope ratios in soil solutions collected within two soil profiles located on two experimental plots of this watershed, along with the analysis of soil samples and vegetation samples from these two plots. The depth variation of elemental concentrations of soil solutions confirms the important influence of the vegetation cycling on the budget of Ca, K, Rb and Sr, whereas Mg and Si budget in soil solutions are quasi exclusively controlled by weathering processes. Variation of Sr, and U isotopic ratios with depth also demonstrates that the sources and biogeochemical processes controlling the Sr budget of soil solutions is different in the uppermost soil horizons and in the deeper ones, and clearly influence by the vegetation cycling. From the obtained data, it can be therefore proposed a scheme where in addition to the external flux associated to the decomposition of organic matter and throughfall, occurs a double lithogenic flux: a surface flux which can be associated to dissolution of secondary minerals contained in fine silt fractions and a deeper one, controlled by water-rock interactions which can mobilize elements from primary minerals like plagioclases or orthose. These results shows also that the Strengbach watershed is in a transient state of weathering with an important loss of nutriments such as Ca in soils solutions since 15years, associated with an increase of a lithogenic flux indicating a recent modification of weathering/dissolution reactions involved in the soil horizons. The origin of the weathering modification could be the consequence of the acid rains on weathering granitic bedrock or a consequence of forest exploitation incompatible with the nutriment reserve of soils with recent plantations of conifer, which impoverish soils.

  11. Mapping communication spaces: The development and use of a tool for analyzing the impact of EHRs on interprofessional collaborative practice.

    PubMed

    Rashotte, Judy; Varpio, Lara; Day, Kathy; Kuziemsky, Craig; Parush, Avi; Elliott-Miller, Pat; King, James W; Roffey, Tyson

    2016-09-01

    Members of the healthcare team must access and share patient information to coordinate interprofessional collaborative practice (ICP). Although some evidence suggests that electronic health records (EHRs) contribute to in-team communication breakdowns, EHRs are still widely hailed as tools that support ICP. If EHRs are expected to promote ICP, researchers must be able to longitudinally study the impact of EHRs on ICP across communication types, users, and physical locations. This paper presents a data collection and analysis tool, named the Map of the Clinical Interprofessional Communication Spaces (MCICS), which supports examining how EHRs impact ICP over time, and across communication types, users, and physical locations. The tool's development evolved during a large prospective longitudinal study conducted at a Canadian pediatric academic tertiary-care hospital. This two-phased study [i.e., pre-implementation (phase 1) and post implementation (phase 2)] of an EHR employed a constructivist grounded theory approach and triangulated data collection strategies (i.e., non-participant observations, interviews, think-alouds, and document analysis). The MCICS was created through a five-step process: (i) preliminary structural development based on the use of the paper-based chart (phase 1); (ii) confirmatory review and modification process (phase 1); (iii) ongoing data collection and analysis facilitated by the map (phase 1); (iv) data collection and modification of map based on impact of EHR (phase 2); and (v) confirmatory review and modification process (phase 2). Creating and using the MCICS enabled our research team to locate, observe, and analyze the impact of the EHR on ICP, (a) across oral, electronic, and paper communications, (b) through a patient's passage across different units in the hospital, (c) across the duration of the patient's stay in hospital, and (d) across multiple healthcare providers. By using the MCICS, we captured a comprehensive, detailed picture of the clinical milieu in which the EHR was implemented, and of the intended and unintended consequences of the EHR's deployment. The map supported our observations and analysis of ICP communication spaces, and of the role of the patient chart in these spaces. If EHRs are expected to help resolve ICP challenges, it is important that researchers be able to longitudinally assess the impact of EHRs on ICP across multiple modes of communication, users, and physical locations. Mapping the clinical communication spaces can help EHR designers, clinicians, educators and researchers understand these spaces, appreciate their complexity, and navigate their way towards effective use of EHRs as means for supporting ICP. We propose that the MCICS can be used "as is" in other academic tertiary-care pediatric hospitals, and can be tailored for use in other healthcare institutions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Gravity-driven pH adjustment for site-specific protein pKa measurement by solution-state NMR

    NASA Astrophysics Data System (ADS)

    Li, Wei

    2017-12-01

    To automate pH adjustment in site-specific protein pKa measurement by solution-state NMR, I present a funnel with two caps for the standard 5 mm NMR tube. The novelty of this simple-to-build and inexpensive apparatus is that it allows automatic gravity-driven pH adjustment within the magnet, and consequently results in a fully automated NMR-monitored pH titration without any hardware modification on the NMR spectrometer.

  13. Agricultural intensification and drought frequency increases may have landscape-level consequences for ephemeral ecosystems.

    PubMed

    Dalu, Tatenda; Wasserman, Ryan J; Dalu, Mwazvita T B

    2017-03-01

    Ephemeral wetlands in arid regions are often degraded or destroyed through poor land-use practice long before they are ever studied or prioritized for conservation. Climate change will likely also have implications for these ecosystems given forecast changes in rainfall patterns in many arid environments. Here, we present a conceptual diagram showing typical and modified ephemeral wetlands in agricultural landscapes and how modification impacts on species diversity and composition. © 2016 John Wiley & Sons Ltd.

  14. [Belated diagnosis of medullar compression in a case of post-polio syndrome].

    PubMed

    Boulay, C; Hamonet, C; Galaup, N; Djindjian, M; Montagne, A; Vivant, R

    2001-03-01

    The physiatrist observes about his practice individuals with sequela of old poliomyelitics. A part of them have unusual fatigue and muscular pains and weakness. The hypothesis of an evolution of neuro-biological mechanism suggested by few authors isn't, actually, demonstrated. More probably, the modifications of lesional and, functional changes with disability observed are the consequence of elderly effects and decreasing of physical activites. We report a case of spinal cord compression by intramedullar tumor, associated with a post-polio syndrome.

  15. Wilckodontics - A Novel Synergy in Time to Save Time

    PubMed Central

    K., Sirisha; M., Srinivas; D., Ravindranath; Gowd, Pratap

    2014-01-01

    The systematic search for improvements in orthodontic therapy is shared by several dental specalities especially periodontics. Rapid orthodontic treatment procedures are now focusing on performing Alveolar Corticotomies (ACS) shortly before the application of orthodontic forces. This method has been suggested to enhance tooth movement and, consequently, reduces orthodontic treatment time as a whole. Thus, this article attempts to review the historical perspective of these therapeutic approaches, discusses the biological reasons underlying its use, mentions its main indications and contraindications and its modifications. PMID:24596806

  16. Casimir effect in the rainbow Einstein's universe

    NASA Astrophysics Data System (ADS)

    Bezerra, V. B.; Mota, H. F.; Muniz, C. R.

    2017-10-01

    In the present paper we investigate the effects caused by the modification of the dispersion relation obtained by solving the Klein-Gordon equation in the closed Einstein's universe in the context of rainbow's gravity models. Thus, we analyse how the quantum vacuum fluctuations of the scalar field are modified when compared with the results obtained in the usual General Relativity scenario. The regularization, and consequently the renormalization, of the vacuum energy is performed adopting the Epstein-Hurwitz and Riemann's zeta functions.

  17. The perceived organizational impact of the gender gap across a Canadian department of medicine and proposed strategies to combat it: a qualitative study.

    PubMed

    Pattani, Reena; Marquez, Christine; Dinyarian, Camellia; Sharma, Malika; Bain, Julie; Moore, Julia E; Straus, Sharon E

    2018-04-10

    Despite the gender parity existing in medical schools for over three decades, women remain underrepresented in academic medical centers, particularly in senior ranks and in leadership roles. This has consequences for patient care, education, research, and workplace culture within healthcare organizations. This study was undertaken to explore the perspectives of faculty members at a single department of medicine on the impact of the existing gender gap on organizational effectiveness and workplace culture, and to identify systems-based strategies to mitigate the gap. The study took place at a large university department of medicine in Toronto, Canada, with six affiliated hospitals. In this qualitative study, semi-structured individual interviews were conducted between May and September 2016 with full-time faculty members who held clinical and university-based appointments. Transcripts of the interviews were analyzed using thematic analysis. Three authors independently reviewed the transcripts to determine a preliminary list of codes and establish a coding framework. A modified audit consensus coding approach was applied; a single analyst reviewed all the transcripts and a second analyst audited 20% of the transcripts in each round of coding. Following each round, inter-rater reliability was determined, discrepancies were resolved through discussion, and modifications were made as needed to the coding framework. The analysis revealed faculty members' perceptions of the gender gap, potential contributing factors, organizational impacts, and possible solutions to bridge the gap. Of the 43 full-time faculty members who participated in the survey (29 of whom self-identified as female), most participants were aware of the existing gender gap within academic medicine. Participants described social exclusion, reinforced stereotypes, and unprofessional behaviors as consequences of the gap on organizational effectiveness and culture. They suggested improvements in (1) the processes for recruitment, hiring, and promotion; (2) inclusiveness of the work environment; (3) structures for mentorship; and (4) ongoing monitoring of the gap. The existing gender gap in academic medicine may have negative consequences for organizational effectiveness and workplace culture but many systems-based strategies to mitigate the gap exist. Although these solutions warrant rigorous evaluation, they are feasible to institute within most healthcare organizations immediately.

  18. A Growing Role for Gender Analysis in Air Pollution Epidemiology

    PubMed Central

    Clougherty, Jane E.

    2010-01-01

    Objective Epidemiologic studies of air pollution effects on respiratory health report significant modification by sex, although results are not uniform. Importantly, it remains unclear whether modifications are attributable to socially derived gendered exposures, to sex-linked physiological differences, or to some interplay thereof. Gender analysis, which aims to disaggregate social from biological differences between males and females, may help to elucidate these possible sources of effect modification. Data sources and data extraction A PubMed literature search was performed in July 2009, using the terms “respiratory” and any of “sex” or “gender” or “men and women” or “boys and girls” and either “PM2.5” (particulate matter ≥ 2.5 μm in aerodynamic diameter) or “NO2” (nitrogen dioxide). I reviewed the identified studies, and others cited therein, to summarize current evidence of effect modification, with attention to authors’ interpretation of observed differences. Owing to broad differences in exposure mixes, outcomes, and analytic techniques, with few studies examining any given combination thereof, meta-analysis was not deemed appropriate at this time. Data synthesis More studies of adults report stronger effects among women, particularly for older persons or where using residential exposure assessment. Studies of children suggest stronger effects among boys in early life and among girls in later childhood. Conclusions The qualitative review describes possible sources of difference in air pollution response between women and men, which may vary by life stage, coexposures, hormonal status, or other factors. The sources of observed effect modifications remain unclear, although gender analytic approaches may help to disentangle gender and sex differences in pollution response. A framework for incorporating gender analysis into environmental epidemiology is offered, along with several potentially useful methods from gender analysis. PMID:20123621

  19. Modification of gray iron produced by induction melting with barium strontium

    NASA Astrophysics Data System (ADS)

    Modzelevskaya, G.; Feoktistov, A. V.; Selyanin, I. F.; Kutsenko, A. I.; Kutsenko, A. A.

    2016-09-01

    The article provides analysis of results of gray iron experimental melts in induction furnace and the following melt modification with barium-strontium carbonate (BSC-2). It is shown that modification positively affects mechanical and casting properties and as-cast iron structure. It was established that BSC-2 granulated immediately prior to use has greater impact on melt than BSC-2 of the same faction, supplied by the manufacturer.

  20. Attitudes Toward Genetic Modification Research: An Analysis of the Views of the Sputnik Generation.

    ERIC Educational Resources Information Center

    Miller, Jon D.

    1982-01-01

    Utilizing data from the 1977 National Assessment of Educational Progress (NAEP) survey of young adults, summarizes attitudes toward genetic modification research and the demographic, educational, and occupational correlates of these attitudes. (Author/SK)

  1. Evolution of long-term coloration trends with biochemically unstable ingredients

    PubMed Central

    Davis, Sarah N.; Andrews, John E.; Badyaev, Alexander V.

    2016-01-01

    The evolutionarily persistent and widespread use of carotenoid pigments in animal coloration contrasts with their biochemical instability. Consequently, evolution of carotenoid-based displays should include mechanisms to accommodate or limit pigment degradation. In birds, this could involve two strategies: (i) evolution of a moult immediately prior to the mating season, enabling the use of particularly fast-degrading carotenoids and (ii) evolution of the ability to stabilize dietary carotenoids through metabolic modification or association with feather keratins. Here, we examine evolutionary lability and transitions between the two strategies across 126 species of birds. We report that species that express mostly unmodified, fast-degrading, carotenoids have pre-breeding moults, and a particularly short time between carotenoid deposition and the subsequent breeding season. Species that expressed mostly slow-degrading carotenoids in their plumage accomplished this through increased metabolic modification of dietary carotenoids, and the selective expression of these slow-degrading compounds. In these species, the timing of moult was not associated with carotenoid composition of plumage displays. Using repeated samples from individuals of one species, we found that metabolic modification of dietary carotenoids significantly slowed their degradation between moult and breeding season. Thus, the most complex and colourful ornamentation is likely the most biochemically stable in birds, and depends less on ecological factors, such as moult timing and migration tendency. We suggest that coevolution of metabolic modification, selective expression and biochemical stability of plumage carotenoids enables the use of unstable pigments in long-term evolutionary trends in plumage coloration. PMID:27194697

  2. Effects of preparation relief and flow channels on seating full coverage castings during cementation.

    PubMed

    Webb, E L; Murray, H V; Holland, G A; Taylor, D F

    1983-06-01

    Machined steel dies were used to study the effects of three die modifications on seating full coverage castings during cementation. The die modifications consisted of occlusal channels, occlusal surface relief, and axial channels. Fourteen specimens having one or more forms of die modification were compared with two control specimens having no die modifications. Statistical analysis of the data revealed that the addition of four axial channels to the simulated preparation on the steel die produced a significant reduction in the mean marginal discrepancy during cementation. Occlusal modifications alone failed to produce significant reductions in marginal discrepancies when compared with the control specimens. Occlusal modifications in conjunction with axial channels failed to produce further significant reductions in marginal discrepancies when compared with those reductions observed in specimens having only axial channels.

  3. The evolutionary implications of epigenetic inheritance.

    PubMed

    Jablonka, Eva

    2017-10-06

    The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

  4. 78 FR 2992 - Agency Information Collection Activities; Proposed Collection; Comment Request; Distribution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-15

    ... Activities; Proposed Collection; Comment Request; Distribution of Offsite Consequence Analysis Information... Collection Request (ICR), Distribution of Offsite Consequence Analysis Information under Section 112(r)(7)(H... Air Act Section 112(r)(7); Distribution of Off-Site Consequence Analysis Information. CAA section 112...

  5. Modeling uncertainties for tropospheric nitrogen dioxide columns affecting satellite-based inverse modeling of nitrogen oxides emissions

    NASA Astrophysics Data System (ADS)

    Lin, J.-T.; Liu, Z.; Zhang, Q.; Liu, H.; Mao, J.; Zhuang, G.

    2012-12-01

    Errors in chemical transport models (CTMs) interpreting the relation between space-retrieved tropospheric column densities of nitrogen dioxide (NO2) and emissions of nitrogen oxides (NOx) have important consequences on the inverse modeling. They are however difficult to quantify due to lack of adequate in situ measurements, particularly over China and other developing countries. This study proposes an alternate approach for model evaluation over East China, by analyzing the sensitivity of modeled NO2 columns to errors in meteorological and chemical parameters/processes important to the nitrogen abundance. As a demonstration, it evaluates the nested version of GEOS-Chem driven by the GEOS-5 meteorology and the INTEX-B anthropogenic emissions and used with retrievals from the Ozone Monitoring Instrument (OMI) to constrain emissions of NOx. The CTM has been used extensively for such applications. Errors are examined for a comprehensive set of meteorological and chemical parameters using measurements and/or uncertainty analysis based on current knowledge. Results are exploited then for sensitivity simulations perturbing the respective parameters, as the basis of the following post-model linearized and localized first-order modification. It is found that the model meteorology likely contains errors of various magnitudes in cloud optical depth, air temperature, water vapor, boundary layer height and many other parameters. Model errors also exist in gaseous and heterogeneous reactions, aerosol optical properties and emissions of non-nitrogen species affecting the nitrogen chemistry. Modifications accounting for quantified errors in 10 selected parameters increase the NO2 columns in most areas with an average positive impact of 18% in July and 8% in January, the most important factor being modified uptake of the hydroperoxyl radical (HO2) on aerosols. This suggests a possible systematic model bias such that the top-down emissions will be overestimated by the same magnitude if the model is used for emission inversion without corrections. The modifications however cannot eliminate the large model underestimates in cities and other extremely polluted areas (particularly in the north) as compared to satellite retrievals, likely pointing to underestimates of the a priori emission inventory in these places with important implications for understanding of atmospheric chemistry and air quality. Note that these modifications are simplified and should be interpreted with caution for error apportionment.

  6. Illinois Precipitation Research: A Focus on Cloud and Precipitation Modification.

    NASA Astrophysics Data System (ADS)

    Changnon, Stanley A.; Czys, Robert R.; Scott, Robert W.; Westcott, Nancy E.

    1991-05-01

    At the heart of the 40-year atmospheric research endeavors of the Illinois State Water Survey have been studies to understand precipitation processes in order to learn how precipitation is modified purposefully and accidentally, and to measure the physical and socio-economic consequences of cloud and precipitation modification. Major field and laboratory activities of past years or briefly treated as a basis for describing the key findings of the past ten years. Recent studies of inadvertent and purposeful cloud and rain modification and their effects are emphasized, including a 1989 field project conducted in Illinois and key findings from an on-going exploratory experiment addressing cloud and rain modification. Results are encouraging for the use of dynamic seeding on summer cumuliform clouds of the Midwest.Typical in-cloud results at 10°C reveal multiple updrafts that tend to be filled with large amounts of supercooled drizzle and raindrops. Natural ice production is vigorous, and initial concentrations are larger than expected from ice nuclei. However, natural ice production is not so vigorous as to preclude opportunities for seeding. Radar-based studies of such clouds reveal that their echo cores usually can be identified prior to desired seeding times, which is significant for the evaluation of their behavior. Cell characteristics show considerable variance under different types of meteorological conditions. Analysis of cell mergers reveals that under conditions of weak vertical shear, mid-level intercell flow at 4 km occurs as the reflectivity bridge between cells rapidly intensifies. The degree of intensification of single-echo cores after they merge is strongly related to the age and vigor of the cores before they join. Hence, cloud growth may be enhanced if seeding can encourage echo cores to merge at critical times. Forecasting research has developed a technique for objectively distinguishing between operational seeding and nonoperational days and for objectively predicting maximum cloud-top height and seeding suitability. An accuracy rate of up to 60% in predicting maximum echo-top height using four categories has been achieved and suggests its use as a covariate in future experimentation. Impact studies illustrate that sizable summer rain increases would be necessary to produce economically beneficial outcomes for Corn Belt agriculture. Increases of 25% in July rainfall across certain high-production crop districts of the Corn Belt would produce economic effects realized nationally.

  7. Inhibition of Clostridium difficile toxin A and B by 1,2-cyclohexanedione modification of an arginine residue.

    PubMed

    Balfanz, J; Rautenberg, P

    1989-12-29

    Toxin A (enterotoxin) and toxin B (cytotoxin) of Clostridium difficile were both inactivated by the arginine specific reagent 1,2-cyclohexanedione. Molecular stability during the inactivation process was demonstrated by SDS-PAGE analysis showing the same migration rates for modified and unmodified forms of the 230 kDa toxin A and of the 250 kDa toxin B. Cytotoxicity of both toxins as well as mouse lethality of the enterotoxin were drastically decreased as a result of the arginine modification. The reaction followed pseudo-first-order kinetics. Analysis of the data suggested that modification of a single arginine residue was sufficient to abolish the activity of both toxins.

  8. Strong Cation Exchange Chromatography in Analysis of Posttranslational Modifications: Innovations and Perspectives

    PubMed Central

    Edelmann, Mariola J.

    2011-01-01

    Strong cation exchange (SCX) chromatography has been utilized as an excellent separation technique that can be combined with reversed-phase (RP) chromatography, which is frequently used in peptide mass spectrometry. Although SCX is valuable as the second component of such two-dimensional separation methods, its application goes far beyond efficient fractionation of complex peptide mixtures. Here I describe how SCX facilitates mapping of the protein posttranslational modifications (PTMs), specifically phosphorylation and N-terminal acetylation. The SCX chromatography has been mainly used for enrichment of these two PTMs, but it might also be beneficial for high-throughput analysis of other modifications that alter the net charge of a peptide. PMID:22174558

  9. Recent Achievements in Characterizing the Histone Code and Approaches to Integrating Epigenomics and Systems Biology.

    PubMed

    Janssen, K A; Sidoli, S; Garcia, B A

    2017-01-01

    Functional epigenetic regulation occurs by dynamic modification of chromatin, including genetic material (i.e., DNA methylation), histone proteins, and other nuclear proteins. Due to the highly complex nature of the histone code, mass spectrometry (MS) has become the leading technique in identification of single and combinatorial histone modifications. MS has now overcome antibody-based strategies due to its automation, high resolution, and accurate quantitation. Moreover, multiple approaches to analysis have been developed for global quantitation of posttranslational modifications (PTMs), including large-scale characterization of modification coexistence (middle-down and top-down proteomics), which is not currently possible with any other biochemical strategy. Recently, our group and others have simplified and increased the effectiveness of analyzing histone PTMs by improving multiple MS methods and data analysis tools. This review provides an overview of the major achievements in the analysis of histone PTMs using MS with a focus on the most recent improvements. We speculate that the workflow for histone analysis at its state of the art is highly reliable in terms of identification and quantitation accuracy, and it has the potential to become a routine method for systems biology thanks to the possibility of integrating histone MS results with genomics and proteomics datasets. © 2017 Elsevier Inc. All rights reserved.

  10. Comparative analysis of lignin peroxidase and manganese peroxidase activity on coniferous and deciduous wood using ToF-SIMS.

    PubMed

    MacDonald, Jacqueline; Goacher, Robyn E; Abou-Zaid, Mamdouh; Master, Emma R

    2016-09-01

    White-rot fungi are distinguished by their ability to efficiently degrade lignin via lignin-modifying type II peroxidases, including manganese peroxidase (MnP) and lignin peroxidase (LiP). In the present study, time-of flight secondary ion mass spectrometry (ToF-SIMS) was used to evaluate lignin modification in three coniferous and three deciduous wood preparations following treatment with commercial preparations of LiP and MnP from two different white-rot fungi. Percent modification of lignin was calculated as a loss of intact methoxylated lignin over nonfunctionalized aromatic rings, which is consistent with oxidative cleavage of methoxy moieties within the lignin structure. Exposure to MnP resulted in greater modification of lignin in coniferous compared to deciduous wood (28 vs. 18 % modification of lignin); and greater modification of G-lignin compared to S-lignin within the deciduous wood samples (21 vs. 12 %). In contrast, exposure to LiP resulted in similar percent modification of lignin in all wood samples (21 vs 22 %), and of G- and S-lignin within the deciduous wood (22 vs. 23 %). These findings suggest that the selected MnP and LiP may particularly benefit delignification of coniferous and deciduous wood, respectively. Moreover, the current analysis further demonstrates the utility of ToF-SIMS for characterizing enzymatic modification of lignin in wood fibre along with potential advantages over UV and HPCL-MS detection of solubilized delignification products.

  11. Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring

    PubMed Central

    Zumbrun, Elizabeth E.; Sido, Jessica M.; Nagarkatti, Prakash S.

    2015-01-01

    Use of marijuana during pregnancy is fairly commonplace and can be expected increase in frequency as more states legalize its recreational use. The cannabinoids present in marijuana have been shown to be immunosuppressive, yet the effect of prenatal exposure to cannabinoids on the immune system of the developing fetus, its long term consequences during adult stage of life, and transgenerational effects have not been well characterized. Confounding factors such as coexisting drug use make the impact of cannabis use on progeny inherently difficult to study in a human population. Data from various animal models suggests that in utero exposure to cannabinoids results in profound T cell dysfunction and a greatly reduced immune response to viral antigens. Furthermore, evidence from animal studies indicates that the immunosuppressive effects of cannabinoids can be mediated through epigenetic mechanisms such as altered microRNA, DNA methylation and histone modification profiles. Such studies support the hypothesis that that parental or prenatal exposure to cannabis can trigger epigenetic changes that could have significant immunological consequences for offspring as well as long term transgenerational effects. PMID:25618446

  12. MODFLOW-CDSS, a version of MODFLOW-2005 with modifications for Colorado Decision Support Systems

    USGS Publications Warehouse

    Banta, Edward R.

    2011-01-01

    MODFLOW-CDSS is a three-dimensional, finite-difference groundwater-flow model based on MODFLOW-2005, with two modifications. The first modification is the introduction of a Partition Stress Boundaries capability, which enables the user to partition a selected subset of MODFLOW's stress-boundary packages, with each partition defined by a separate input file. Volumetric water-budget components of each partition are tracked and listed separately in the volumetric water-budget tables. The second modification enables the user to specify that execution of a simulation should continue despite failure of the solver to satisfy convergence criteria. This modification is particularly intended to be used in conjunction with automated model-analysis software; its use is not recommended for other purposes.

  13. Covalent Surface Modifications of Carbon Nanotubes.

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

    Pavia Sanders, Adriana; O'Bryan, Greg

    A report meant to document the chemistries investigated by the author for covalent surface modification of CNTs. Oxidation, cycloaddition, and radical reactions were explored to determine their success at covalently altering the CNT surface. Characterization through infrared spectroscopy, Raman spectroscopy, and thermo gravimetric analysis was performed in order to determine the success of the chemistries employed. This report is not exhaustive and was performed for CNT surface modification exploration as it pertains to the "Next Gen" project.

  14. Direct gas injection method: A simple modification to an elemental analyzer/isotope ratio mass spectrometer for stable isotope analysis of N and C from N2O and CO2 gases in nanomolar concentrations

    EPA Science Inventory

    A simple modification to the Elemental Analyzer coupled to Isotope Ratio Mass-Spectrometer (EA-IRMS) setup is described. This modification allows the users to measure nitrous oxide (N2O) and carbon dioxide (CO2) by injecting the gases directly into an online injector placed befor...

  15. Fuel Savings through Aircraft Modification: A Cost Analysis

    DTIC Science & Technology

    2009-06-01

    tanker aircraft with winglets and submit a report to the congressional defense committees by May 1, 2009. This research summarizes the main issues...that decision-makers should consider in the investment in a winglet modification program. The factors that should be included in any decision, such...addition of winglets to the KC-135R could reduce the future fuel expenditures between $177 million and $1.1 billion over the modification costs by 2042

  16. Conceptual design study of a Harrier V/STOL research aircraft

    NASA Technical Reports Server (NTRS)

    Bode, W. E.; Berger, R. L.; Elmore, G. A.; Lacey, T. R.

    1978-01-01

    MCAIR recently completed a conceptual design study to define modification approaches to, and derive planning prices for the conversion of a two place Harrier to a V/STOL control, display and guidance research aircraft. Control concepts such as rate damping, attitude stabilization, velocity command, and cockpit controllers are to be demonstrated. Display formats will also be investigated, and landing, navigation and guidance systems flight tested. The rear cockpit is modified such that it can be quickly adapted to faithfully simulate the controls, displays and handling qualities of a Type A or Type B V/STOL. The safety pilot always has take command capability. The modifications studied fall into two categories: basic modifications and optional modifications. Technical descriptions of the basic modifications and of the optional modifications are presented. The modification plan and schedule as well as the test plan and schedule are presented. The failure mode and effects analysis, aircraft performance, aircraft weight, and aircraft support are discussed.

  17. Longitudinal changes in everyday life after home modifications for people aging with disabilities.

    PubMed

    Petersson, Ingela; Kottorp, Anders; Bergström, Jakob; Lilja, Margareta

    2009-05-01

    To investigate longitudinal impacts of home modifications on the difficulty of performing everyday life tasks for people aging with disabilities, and to investigate whether other factors had any additional impacts on difficulty in everyday life tasks for people receiving home modifications. The sample consisted of 103 persons aging with disabilities and in need of home modifications, divided into an intervention group and a comparison group. The data were first subjected to Rasch analysis and a random coefficient model was used. Participants in the intervention group reported a significantly lower level of difficulty in everyday life tasks compared with those in the comparison group. One confounding factor, number of months waiting for home modification, had an impact on difficulty in everyday life. Home modifications are effective in decreasing difficulty in performing everyday life tasks up to six months after the installation. Furthermore, to be effective home modifications need to be installed in a timely fashion. For each consecutive month the person waited for their home modification the difficulty of performing everyday life tasks increased. Therefore, it is important that home modifications be installed as soon as possible after the need has been identified.

  18. GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

    PubMed

    Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

    2016-06-16

    As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.

  19. Probabilistic Structural Analysis of the SRB Aft Skirt External Fitting Modification

    NASA Technical Reports Server (NTRS)

    Townsend, John S.; Peck, J.; Ayala, S.

    1999-01-01

    NASA has funded several major programs (the PSAM Project is an example) to develop Probabilistic Structural Analysis Methods and tools for engineers to apply in the design and assessment of aerospace hardware. A probabilistic finite element design tool, known as NESSUS, is used to determine the reliability of the Space Shuttle Solid Rocket Booster (SRB) aft skirt critical weld. An external bracket modification to the aft skirt provides a comparison basis for examining the details of the probabilistic analysis and its contributions to the design process.

  20. Mapping Natech risk due to earthquakes using RAPID-N

    NASA Astrophysics Data System (ADS)

    Girgin, Serkan; Krausmann, Elisabeth

    2013-04-01

    Natural hazard-triggered technological accidents (so-called Natech accidents) at hazardous installations are an emerging risk with possibly serious consequences due to the potential for release of hazardous materials, fires or explosions. For the reduction of Natech risk, one of the highest priority needs is the identification of Natech-prone areas and the systematic assessment of Natech risks. With hardly any Natech risk maps existing within the EU the European Commission's Joint Research Centre has developed a Natech risk analysis and mapping tool called RAPID-N, that estimates the overall risk of natural-hazard impact to industrial installations and its possible consequences. The results are presented as risk summary reports and interactive risk maps which can be used for decision making. Currently, RAPID-N focuses on Natech risk due to earthquakes at industrial installations. However, it will be extended to also analyse and map Natech risk due to floods in the near future. The RAPID-N methodology is based on the estimation of on-site natural hazard parameters, use of fragility curves to determine damage probabilities of plant units for various damage states, and the calculation of spatial extent, severity, and probability of Natech events potentially triggered by the natural hazard. The methodology was implemented as a web-based risk assessment and mapping software tool which allows easy data entry, rapid local or regional risk assessment and mapping. RAPID-N features an innovative property estimation framework to calculate on-site natural hazard parameters, industrial plant and plant unit characteristics, and hazardous substance properties. Custom damage states and fragility curves can be defined for different types of plant units. Conditional relationships can be specified between damage states and Natech risk states, which describe probable Natech event scenarios. Natech consequences are assessed using a custom implementation of U.S. EPA's Risk Management Program (RMP) Guidance for Offsite Consequence Analysis methodology. This custom implementation is based on the property estimation framework and allows the easy modification of model parameters and the substitution of equations with alternatives. RAPID-N can be applied at different stages of the Natech risk management process: It allows on the one hand the analysis of hypothetical Natech scenarios to prevent or prepare for a Natech accident by supporting land-use and emergency planning. On the other hand, once a natural disaster occurs RAPID-N can be used for rapidly locating facilities with potential Natech accident damage based on actual natural-hazard information. This provides a means to warn the population in the vicinity of the facilities in a timely manner. This presentation will introduce the specific features of RAPID-N and show the use of the tool by application to a case-study area.

  1. A cost-analysis of complex workplace nutrition education and environmental dietary modification interventions.

    PubMed

    Fitzgerald, Sarah; Kirby, Ann; Murphy, Aileen; Geaney, Fiona; Perry, Ivan J

    2017-01-09

    The workplace has been identified as a priority setting to positively influence individuals' dietary behaviours. However, a dearth of evidence exists regarding the costs of implementing and delivering workplace dietary interventions. This study aimed to conduct a cost-analysis of workplace nutrition education and environmental dietary modification interventions from an employer's perspective. Cost data were obtained from a workplace dietary intervention trial, the Food Choice at Work Study. Micro-costing methods estimated costs associated with implementing and delivering the interventions for 1 year in four multinational manufacturing workplaces in Cork, Ireland. The workplaces were allocated to one of the following groups: control, nutrition education alone, environmental dietary modification alone and nutrition education and environmental dietary modification combined. A total of 850 employees were recruited across the four workplaces. For comparison purposes, total costs were standardised for 500 employees per workplace. The combined intervention reported the highest total costs of €31,108. The nutrition education intervention reported total costs of €28,529. Total costs for the environmental dietary modification intervention were €3689. Total costs for the control workplace were zero. The average annual cost per employee was; combined intervention: €62, nutrition education: €57, environmental modification: €7 and control: €0. Nutritionist's time was the main cost contributor across all interventions, (ranging from 53 to 75% of total costs). Within multi-component interventions, the relative cost of implementing and delivering nutrition education elements is high compared to environmental modification strategies. A workplace environmental modification strategy added marginal additional cost, relative to the control. Findings will inform employers and public health policy-makers regarding the economic feasibility of implementing and scaling dietary interventions. Current Controlled Trials: ISRCTN35108237 . Date of registration: The trial was retrospectively registered on 02/07/2013.

  2. Automated Solid-Phase Protein Modification with Integrated Enzymatic Digest for Reaction Validation: Application of a Compartmented Microfluidic Reactor for Rapid Optimization and Analysis of Protein Biotinylation

    PubMed Central

    Fraas, Regina; Diehm, Juliane; Franzreb, Matthias

    2017-01-01

    Protein modification by covalent coupling of small ligands or markers is an important prerequisite for the use of proteins in many applications. Well-known examples are the use of proteins with fluorescent markers in many in vivo experiments or the binding of biotinylated antibodies via biotin–streptavidin coupling in the frame of numerous bioassays. Multiple protocols were established for the coupling of the respective molecules, e.g., via the C and N-terminus, or via cysteines and lysines exposed at the protein surface. Still, in most cases the conditions of these standard protocols are only an initial guess. Optimization of the coupling parameters like reagent concentrations, pH, or temperature may strongly increase coupling yield and the biological activity of the modified protein. In order to facilitate the process of optimizing coupling conditions, a method was developed which uses a compartmented microfluidic reactor for the rapid screening of different coupling conditions. In addition, the system allows for the integration of an enzymatic digest of the modified protein directly after modification. In combination with a subsequent MALDI-TOF analysis of the resulting fragments, this gives a fast and detailed picture not only of the number and extent of the generated modifications but also of their position within the protein sequence. The described process was demonstrated for biotinylation of green fluorescent protein. Different biotin-excesses and different pH-values were tested in order to elucidate the influence on the modification extent and pattern. In addition, the results of solid-phase based modifications within the microfluidic reactor were compared to modification patterns resulting from coupling trials with unbound protein. As expected, modification patterns of immobilized proteins showed clear differences to the ones of dissolved proteins. PMID:29181376

  3. Preparation of highly hydrophobic cotton fabrics by modification with bifunctional silsesquioxanes in the sol-gel process

    NASA Astrophysics Data System (ADS)

    Przybylak, Marcin; Maciejewski, Hieronim; Dutkiewicz, Agnieszka

    2016-11-01

    The surface modification of cotton fabrics was carried out using two types of bifunctional fluorinated silsesquioxanes with different ratios of functional groups. The modification was performed either by one- or two-step process. Two methods, the sol-gel and the dip coating method were used in different configurations. The heat treatment and the washing process were applied after modification. The wettability of cotton fabric was evaluated by measuring water contact angles (WCA). Changes in the surface morphology were examined by scanning electron microscopy (SEM, SEM-LFD) and atomic force microscopy (AFM). Moreover, the modified fabrics were subjected to analysis of elemental composition of the applied coatings using SEM-EDS techniques. Highly hydrophobic textiles were obtained in all cases studied and one of the modifications resulted in imparting superhydrophobic properties. Most of impregnated textiles remained hydrophobic even after multiple washing process which shows that the studied modification is durable.

  4. Optimal Control Modification Adaptive Law for Time-Scale Separated Systems

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan T.

    2010-01-01

    Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. A model matching conditions in the transformed time coordinate results in an increase in the actuator command that effectively compensate for the slow actuator dynamics. Simulations demonstrate effectiveness of the method.

  5. Optimal Control Modification for Time-Scale Separated Systems

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan T.

    2012-01-01

    Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. A model matching conditions in the transformed time coordinate results in an increase in the actuator command that effectively compensate for the slow actuator dynamics. Simulations demonstrate effectiveness of the method.

  6. The Expanding Landscape of the Thiol Redox Proteome*

    PubMed Central

    Yang, Jing; Carroll, Kate S.; Liebler, Daniel C.

    2016-01-01

    Cysteine occupies a unique place in protein chemistry. The nucleophilic thiol group allows cysteine to undergo a broad range of redox modifications beyond classical thiol-disulfide redox equilibria, including S-sulfenylation (-SOH), S-sulfinylation (-SO2H), S-sulfonylation (-SO3H), S-nitrosylation (-SNO), S-sulfhydration (-SSH), S-glutathionylation (-SSG), and others. Emerging evidence suggests that these post-translational modifications (PTM) are important in cellular redox regulation and protection against oxidative damage. Identification of protein targets of thiol redox modifications is crucial to understanding their roles in biology and disease. However, analysis of these highly labile and dynamic modifications poses challenges. Recent advances in the design of probes for thiol redox forms, together with innovative mass spectrometry based chemoproteomics methods make it possible to perform global, site-specific, and quantitative analyses of thiol redox modifications in complex proteomes. Here, we review chemical proteomic strategies used to expand the landscape of thiol redox modifications. PMID:26518762

  7. 14 CFR 152.605 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Consideration of using alternative, renewable energy sources. Major building modification means modification of... AIRPORT AID PROGRAM Energy Conservation in Airport Aid Program § 152.605 Definitions. As used in this... the program, which will exceed $200,000 in construction cost. Energy assessment means an analysis of...

  8. Resolution effects in the hybrid strong/weak coupling model

    NASA Astrophysics Data System (ADS)

    Hulcher, Zachary; Pablos, Daniel; Rajagopal, Krishna

    2018-03-01

    Within the context of a hybrid strong/weak coupling model of jet quenching, we study the consequences of the fact that the plasma produced in a heavy ion collision cannot resolve the substructure of a collimated parton shower propagating through it with arbitrarily fine spatial resolution. We introduce a screening length parameter, L res, proportional to the inverse of the local temperature in the plasma, estimating a range for the value of the proportionality constant via comparing weakly coupled QCD calculations and holographic calculations appropriate in strongly coupled plasma. We then modify the hybrid model so that when a parton in a jet shower splits, its two offspring are initially treated as unresolved, and are only treated as two separate partons losing energy independently after they are separated by a distance L res. This modification delays the quenching of partons with intermediate energy, resulting in the survival of more hadrons in the final state with p T in the several GeV range. We analyze the consequences of different choices for the value of the resolution length, L res, and demonstrate that introducing a nonzero L res results in modifications to the jet shapes and jet fragmentations functions, as it makes it more probable for particles carrying a small fraction of the jet energy at larger angles from the jet axis to survive their passage through the quark-gluon plasma. These effects are, however, small in magnitude, something that we confirm via checking for effects on missing- p T observables.

  9. Protein lipoxidation: Detection strategies and challenges

    PubMed Central

    Aldini, Giancarlo; Domingues, M. Rosário; Spickett, Corinne M.; Domingues, Pedro; Altomare, Alessandra; Sánchez-Gómez, Francisco J.; Oeste, Clara L.; Pérez-Sala, Dolores

    2015-01-01

    Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adaptive mechanisms, as exemplified by lipoxidation of Ras proteins or of the cytoskeletal protein vimentin, both of which behave as sensors of electrophilic species. Nevertheless, increased lipoxidation under pathological conditions may lead to deleterious effects on protein structure or aggregation. This can result in impaired degradation and accumulation of abnormally folded proteins contributing to pathophysiology, as may occur in neurodegenerative diseases. Identification of the protein targets of lipoxidation and its functional consequences under pathophysiological situations can unveil the modification patterns associated with the various outcomes, as well as preventive strategies or potential therapeutic targets. Given the wide structural variability of lipid moieties involved in lipoxidation, highly sensitive and specific methods for its detection are required. Derivatization of reactive carbonyl species is instrumental in the detection of adducts retaining carbonyl groups. In addition, use of tagged derivatives of electrophilic lipids enables enrichment of lipoxidized proteins or peptides. Ultimate confirmation of lipoxidation requires high resolution mass spectrometry approaches to unequivocally identify the adduct and the targeted residue. Moreover, rigorous validation of the targets identified and assessment of the functional consequences of these modifications are essential. Here we present an update on methods to approach the complex field of lipoxidation along with validation strategies and functional assays illustrated with well-studied lipoxidation targets. PMID:26072467

  10. The Health Impacts of Climate Change: A Continuing Medical Education Needs Assessment Framework.

    PubMed

    Valois, Pierre; Blouin, Patrick; Ouellet, Claudine; Renaud, Jean-Sébastien; Bélanger, Diane; Gosselin, Pierre

    2016-01-01

    As the health consequences of climate change (CC) will likely become more manifest in the future, family physicians have to be knowledgeable about these impacts and the ways in which they can affect their patients. The main aim of this study was to propose a competency framework and questionnaire used to conduct a needs analysis to identify and prioritize family physicians' real educational needs regarding the health impacts of CC. A mixed method combining a qualitative interview and a quantitative online questionnaire was used (n = 24 physicians). The interview assessed key beliefs related to participating in an online continuing medical education (eCME) activity on the health impacts of climate change, and the perception of the key factors or conditions required to ensure the family physicians' satisfaction with this eCME activity. The questionnaire assessed the current and desired levels of competency on five general training themes: general knowledge about CC; heat-related illnesses; CC, extreme weather events and modification of vector-borne and zoonotic diseases; CC, extreme weather events and modification of water-borne diseases; and mental health impacts of natural disasters. Results revealed the need for improved medical education on climate change and health. Results also add to the literature by showing that a 3-hour eCME activity covering these topics would be useful and would allow family physicians to use this knowledge in their daily practice, notably through prevention and counseling. Introducing a CME needs assessment framework and a generic instrument that reflects family physicians' needs regarding the health impacts of CC has the added advantage of standardizing the assessment procedure.

  11. Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

    PubMed

    Arefin, Tanzil Mahmud; Mechling, Anna E; Meirsman, Aura Carole; Bienert, Thomas; Hübner, Neele Saskia; Lee, Hsu-Lei; Ben Hamida, Sami; Ehrlich, Aliza; Roquet, Dan; Hennig, Jürgen; von Elverfeldt, Dominik; Kieffer, Brigitte Lina; Harsan, Laura-Adela

    2017-10-01

    Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88 -/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.

  12. Modern proteomic methodologies for the characterization of lactosylation protein targets in milk.

    PubMed

    Arena, Simona; Renzone, Giovanni; Novi, Gianfranco; Paffetti, Alessandro; Bernardini, Giulia; Santucci, Annalisa; Scaloni, Andrea

    2010-10-01

    Heat treatment of milk induces the Maillard reaction between lactose and proteins; in this context, β-lactoglobulin and α-lactalbumin adducts have been used as markers to monitor milk quality. Since some milk proteins have been reported as essential for the delivery of microelements and, being resistant against proteolysis in the gastrointestinal tract, also contributing to the acquired immune response against pathogens and the stimulation of cellular proliferation, it is crucial to systematically determine the milk subproteome affected by the Maillard reaction for a careful evaluation of aliment functional properties. This is more important when milk is the unique nutritional source, as in infant diet. To this purpose, a combination of proteomic procedures based on analyte capture by combinatorial peptide ligand libraries, selective trapping of lactosylated peptides by m-aminophenylboronic acid-agarose chromatography and collision-induced dissociation and electron transfer dissociation MS was used for systematic identification of the lactosylated proteins in milk samples subjected to different thermal treatments. An exhaustive modification of proteins was observed in milk powdered preparations for infant nutrition. Globally, this approach allowed the identification of 271 non-redundant modification sites in 33 milk proteins, which also included low-abundance components involved in nutrient delivery, defence response against virus/microorganisms and cellular proliferative events. A comparison of the modified peptide identification percentages resulting from electron transfer dissociation or collision-induced dissociation fragmentation spectra confirmed the first activation mode as most advantageous for the analysis of lactosylated proteins. Nutritional, biological and toxicological consequences of these findings are discussed on the basis of the recent literature on this subject, emphasizing their impact on newborn diet.

  13. Analysis and modification of defective surface aggregates on PCDTBT:PCBM solar cell blends using combined Kelvin probe, conductive and bimodal atomic force microscopy

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

    Noh, Hanaul; Diaz, Alfredo J.; Solares, Santiago D.

    Organic photovoltaic systems comprising donor polymers and acceptor fullerene derivatives are attractive for inexpensive energy harvesting. Extensive research on polymer solar cells has provided insight into the factors governing device-level efficiency and stability. However, the detailed investigation of nanoscale structures is still challenging. Here we demonstrate the analysis and modification of unidentified surface aggregates. The aggregates are characterized electrically by Kelvin probe force microscopy and conductive atomic force microscopy (C-AFM), whereby the correlation between local electrical potential and current confirms a defective charge transport. Bimodal AFM modification confirms that the aggregates exist on top of the solar cell structure, andmore » is used to remove them and to reveal the underlying active layer. The systematic analysis of the surface aggregates suggests that the structure consists of PCBM molecules.« less

  14. Impact of ontology evolution on functional analyses.

    PubMed

    Groß, Anika; Hartung, Michael; Prüfer, Kay; Kelso, Janet; Rahm, Erhard

    2012-10-15

    Ontologies are used in the annotation and analysis of biological data. As knowledge accumulates, ontologies and annotation undergo constant modifications to reflect this new knowledge. These modifications may influence the results of statistical applications such as functional enrichment analyses that describe experimental data in terms of ontological groupings. Here, we investigate to what degree modifications of the Gene Ontology (GO) impact these statistical analyses for both experimental and simulated data. The analysis is based on new measures for the stability of result sets and considers different ontology and annotation changes. Our results show that past changes in the GO are non-uniformly distributed over different branches of the ontology. Considering the semantic relatedness of significant categories in analysis results allows a more realistic stability assessment for functional enrichment studies. We observe that the results of term-enrichment analyses tend to be surprisingly stable despite changes in ontology and annotation.

  15. Analysis and modification of defective surface aggregates on PCDTBT:PCBM solar cell blends using combined Kelvin probe, conductive and bimodal atomic force microscopy

    DOE PAGES

    Noh, Hanaul; Diaz, Alfredo J.; Solares, Santiago D.

    2017-03-08

    Organic photovoltaic systems comprising donor polymers and acceptor fullerene derivatives are attractive for inexpensive energy harvesting. Extensive research on polymer solar cells has provided insight into the factors governing device-level efficiency and stability. However, the detailed investigation of nanoscale structures is still challenging. Here we demonstrate the analysis and modification of unidentified surface aggregates. The aggregates are characterized electrically by Kelvin probe force microscopy and conductive atomic force microscopy (C-AFM), whereby the correlation between local electrical potential and current confirms a defective charge transport. Bimodal AFM modification confirms that the aggregates exist on top of the solar cell structure, andmore » is used to remove them and to reveal the underlying active layer. The systematic analysis of the surface aggregates suggests that the structure consists of PCBM molecules.« less

  16. Analysis and modification of defective surface aggregates on PCDTBT:PCBM solar cell blends using combined Kelvin probe, conductive and bimodal atomic force microscopy

    PubMed Central

    Noh, Hanaul; Diaz, Alfredo J

    2017-01-01

    Organic photovoltaic systems comprising donor polymers and acceptor fullerene derivatives are attractive for inexpensive energy harvesting. Extensive research on polymer solar cells has provided insight into the factors governing device-level efficiency and stability. However, the detailed investigation of nanoscale structures is still challenging. Here we demonstrate the analysis and modification of unidentified surface aggregates. The aggregates are characterized electrically by Kelvin probe force microscopy and conductive atomic force microscopy (C-AFM), whereby the correlation between local electrical potential and current confirms a defective charge transport. Bimodal AFM modification confirms that the aggregates exist on top of the solar cell structure, and is used to remove them and to reveal the underlying active layer. The systematic analysis of the surface aggregates suggests that the structure consists of PCBM molecules. PMID:28382247

  17. Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

    PubMed Central

    Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

    2016-01-01

    Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis. PMID:26776680

  18. RMP Guidance for Warehouses - Chapter 4: Offsite Consequence Analysis

    EPA Pesticide Factsheets

    Offsite consequence analysis (OCA) informs government and the public about potential consequences of an accidental toxic or flammable chemical release at your facility, and consists of a worst-case release scenario and alternative release scenarios.

  19. Genome-wide identification of sweet orange (Citrus sinensis) histone modification gene families and their expression analysis during the fruit development and fruit-blue mold infection process.

    PubMed

    Xu, Jidi; Xu, Haidan; Liu, Yuanlong; Wang, Xia; Xu, Qiang; Deng, Xiuxin

    2015-01-01

    In eukaryotes, histone acetylation and methylation have been known to be involved in regulating diverse developmental processes and plant defense. These histone modification events are controlled by a series of histone modification gene families. To date, there is no study regarding genome-wide characterization of histone modification related genes in citrus species. Based on the two recent sequenced sweet orange genome databases, a total of 136 CsHMs (Citrus sinensis histone modification genes), including 47 CsHMTs (histone methyltransferase genes), 23 CsHDMs (histone demethylase genes), 50 CsHATs (histone acetyltransferase genes), and 16 CsHDACs (histone deacetylase genes) were identified. These genes were categorized to 11 gene families. A comprehensive analysis of these 11 gene families was performed with chromosome locations, phylogenetic comparison, gene structures, and conserved domain compositions of proteins. In order to gain an insight into the potential roles of these genes in citrus fruit development, 42 CsHMs with high mRNA abundance in fruit tissues were selected to further analyze their expression profiles at six stages of fruit development. Interestingly, a numbers of genes were expressed highly in flesh of ripening fruit and some of them showed the increasing expression levels along with the fruit development. Furthermore, we analyzed the expression patterns of all 136 CsHMs response to the infection of blue mold (Penicillium digitatum), which is the most devastating pathogen in citrus post-harvest process. The results indicated that 20 of them showed the strong alterations of their expression levels during the fruit-pathogen infection. In conclusion, this study presents a comprehensive analysis of the histone modification gene families in sweet orange and further elucidates their behaviors during the fruit development and the blue mold infection responses.

  20. Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis.

    PubMed

    Xu, Shou-Ling; Chalkley, Robert J; Maynard, Jason C; Wang, Wenfei; Ni, Weimin; Jiang, Xiaoyue; Shin, Kihye; Cheng, Ling; Savage, Dasha; Hühmer, Andreas F R; Burlingame, Alma L; Wang, Zhi-Yong

    2017-02-21

    Genetic studies have shown essential functions of O-linked N -acetylglucosamine (O-GlcNAc) modification in plants. However, the proteins and sites subject to this posttranslational modification are largely unknown. Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level.

  1. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model.

    PubMed

    Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

    2016-04-30

    Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q²) value of 0.597 and correlation coefficients (r²) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q² and r² of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r²pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity.

  2. Sequence-Specific Targeting of Dosage Compensation in Drosophila Favors an Active Chromatin Context

    PubMed Central

    Gelbart, Marnie; Tolstorukov, Michael Y.; Plachetka, Annette; Kharchenko, Peter V.; Jung, Youngsook L.; Gorchakov, Andrey A.; Larschan, Erica; Gu, Tingting; Minoda, Aki; Riddle, Nicole C.; Schwartz, Yuri B.; Elgin, Sarah C. R.; Karpen, Gary H.; Pirrotta, Vincenzo; Kuroda, Mitzi I.; Park, Peter J.

    2012-01-01

    The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at “entry sites” that contain a consensus sequence motif (“MSL recognition element” or MRE). However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex) and female Kc cells (which lack the complex), we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome. PMID:22570616

  3. Domestication of the Cardiac Mitochondrion for Energy Conversion

    PubMed Central

    Balaban, Robert S.

    2009-01-01

    The control of mitochondria energy conversion by cytosolic processes is reviewed. The nature of the cytosolic and mitochondrial potential energy homeostasis over wide ranges of energy utilization is reviewed and the consequences of this homeostasis in the control network are discussed. An analysis of the major candidate cytosolic signaling molecules ADP, Pi and Ca2+ are reviewed based on the magnitude and source of the cytosolic concentration changes as well as the potential targets of action within the mitochondrial energy conversion system. Based on this analysis, Ca2+ is the best candidate as a cytosolic signaling molecule for this process based on its ability to act as both a feed-forward and feed-back indicator of ATP hydrolysis and numerous targets within the matrix to provide a balanced activation of ATP production. These targets include numerous dehydrogenases and the F1-F0-ATPase. Pi is also a good candidate since it is an early signal of a mismatch between cytosolic ATP production and ATP synthesis in the presence of creatine kinase and has multiple targets within oxidative phosphorylation including NADH generation, electron flux in the cytochrome chain and a substrate for the F1-F0-ATPase. The mechanism of the coordinated activation of oxidative phosphorylation by these signaling molecules in discussed in light of the recent discoveries of extensive protein phosphorylation sites and other post-translational modifications. From this review it is clear that the control network associated with the maintenance of the cytosolic potential energy homeostasis is extremely complex with multiple pathways orchestrated to balance the sinks and sources in this system. New tools are needed to image and monitor metabolites within subcellular compartments to resolve many of these issues as well as the functional characterization of the numerous matrix post-translational events being discovered along with the enzymatic processes generating and removing these protein modifications. PMID:19265699

  4. Speech transformations based on a sinusoidal representation

    NASA Astrophysics Data System (ADS)

    Quatieri, T. E.; McAulay, R. J.

    1986-05-01

    A new speech analysis/synthesis technique is presented which provides the basis for a general class of speech transformation including time-scale modification, frequency scaling, and pitch modification. These modifications can be performed with a time-varying change, permitting continuous adjustment of a speaker's fundamental frequency and rate of articulation. The method is based on a sinusoidal representation of the speech production mechanism that has been shown to produce synthetic speech that preserves the waveform shape and is essentially perceptually indistinguishable from the original. Although the analysis/synthesis system originally was designed for single-speaker signals, it is equally capable of recovering and modifying nonspeech signals such as music; multiple speakers, marine biologic sounds, and speakers in the presence of interferences such as noise and musical backgrounds.

  5. Implications of male circumcision for women in Papua New Guinea: a transformational grounded theory study.

    PubMed

    Redman-MacLaren, Michelle; Mills, Jane; Tommbe, Rachael; MacLaren, David; Speare, Rick; McBride, William J H

    2017-07-27

    Male circumcision reduces the risk of female-to-male transmission of human immunodeficiency virus (HIV) and is being explored for HIV prevention in Papua New Guinea (PNG). PNG has a concentrated HIV epidemic which is largely heterosexually transmitted. There are a diverse range of male circumcision and penile modification practices across PNG. Exploring the implications of male circumcision for women in PNG is important to inform evidence-based health policy that will result in positive, intended consequences. The transformational grounded theory study incorporated participatory action research and decolonizing methodologies. In Phase One, an existing data set from a male circumcision study of 861 male and 519 female participants was theoretically sampled and analyzed for women's understanding and experience of male circumcision. In Phase Two of the study, primary data were co-generated with 64 women in seven interpretive focus group discussions and 11 semi-structured interviews to develop a theoretical model of the processes used by women to manage the outcomes of male circumcision. In Phase Three participants assisted to refine the developing transformational grounded theory and identify actions required to improve health. Many women know a lot about male circumcision and penile modification and the consequences for themselves, their families and communities. Their ability to act on this knowledge is determined by numerous social, cultural and economic factors. A transformational grounded theory was developed with connecting categories of: Women Know a Lot, Increasing Knowledge; Increasing Options; and Acting on Choices. Properties and dimensions of each category are represented in the model, along with the intervening condition of Safety. The condition of Safety contextualises the overarching lived realty for women in PNG, enables the inclusion of men in the transformational grounded theory model, and helps to explain relationships between men and women. The theory presents the core category as Power of Choice. This transformational grounded theory provides a means to explore how women experience male circumcision and penile modification in PNG, including for HIV prevention. Women who have had opportunities for education have a greater range of choices and an increased opportunity to act upon these choices. However, women can only exercise their power of choice in the context of safety. The concept of Peace drawn from the Social Determinants of Health is applied in order to extend the explanatory power of the transformational grounded theory. This study shows that women's ambivalence about male circumcision is often related to lack of safety, a consequence of gender inequality in PNG.

  6. 2'-O-[2-[2-(N,N-Dimethylamino)ethoxy]ethyl] Modified Antisense Oligonucleotides: Symbiosis of Charge Interaction Factors and Stereoelectronic Effects

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

    Prhavc, M.; Prakash, T.P.; Minasov, G.

    Oligonucleotides with a novel, 2'-O-[2-[2-(N,N-dimethylamino)ethoxy]ethyl] (2'-O-DMAEOE) modification have been synthesized. This modification, a cationic analogue of the 2'-O-(2-methoxyethyl) (2'-O-MOE) modification, exhibits high binding affinity to target RNA (but not to DNA) and exceptional resistance to nuclease degradation. Analysis of the crystal structure of a self-complementary oligonucleotide containing a single 2'-O-DMAEOE modification explains the importance of charge factors and gauche effects on the observed antisense properties. 2'-O-DMAEOE modified oligonucleotides are ideal candidates for antisense drugs.

  7. 48 CFR 31.103 - Contracts with commercial organizations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contracts with commercial... with commercial organizations. This category includes all contracts and contract modifications for... modifications with commercial organizations whenever cost analysis is performed as required by 15.404-1(c). (b...

  8. A view inside the nature of protein crystals

    NASA Astrophysics Data System (ADS)

    Oswald, R.; Pietzsch, M.; Ulrich, J.

    2017-07-01

    In this work a fundamental analysis of protein crystal modifications was presented to compare and confirm the components of protein crystal modifications. The result is that a protein crystal contains besides the protein, the precipitant and water. A mass spectrometer coupled to a thermogravimetry device was used to confirm the different waters (free water -the chosen buffer- and bound water) inside the crystals. Here the biggest amount of water is the free water (the buffer) with an amount of approximately 35%. The bound water (in the sense of a hydrate) has only an amount of about 1-1.5%. Furthermore, an x-ray analysis to confirm the influence range of pH value on the stability of one crystal modification for the understanding of effects on dissolution mechanism of protein crystals was investigated. The crystals of the tetragonal modification crystallized at pH 4.7, 4.85, 5.0, 5.15 and 5.3 maintain according to the x-ray measurements the same lattice parameters. The measured data are discussed.

  9. Effects of computer-based training on procedural modifications to standard functional analyses.

    PubMed

    Schnell, Lauren K; Sidener, Tina M; DeBar, Ruth M; Vladescu, Jason C; Kahng, SungWoo

    2018-01-01

    Few studies have evaluated methods for training decision-making when functional analysis data are undifferentiated. The current study evaluated computer-based training to teach 20 graduate students to arrange functional analysis conditions, analyze functional analysis data, and implement procedural modifications. Participants were exposed to training materials using interactive software during a 1-day session. Following the training, mean scores on the posttest, novel cases probe, and maintenance probe increased for all participants. These results replicate previous findings during a 1-day session and include a measure of participant acceptability of the training. Recommendations for future research on computer-based training and functional analysis are discussed. © 2017 Society for the Experimental Analysis of Behavior.

  10. Probabilistic Structural Analysis of the Solid Rocket Booster Aft Skirt External Fitting Modification

    NASA Technical Reports Server (NTRS)

    Townsend, John S.; Peck, Jeff; Ayala, Samuel

    2000-01-01

    NASA has funded several major programs (the Probabilistic Structural Analysis Methods Project is an example) to develop probabilistic structural analysis methods and tools for engineers to apply in the design and assessment of aerospace hardware. A probabilistic finite element software code, known as Numerical Evaluation of Stochastic Structures Under Stress, is used to determine the reliability of a critical weld of the Space Shuttle solid rocket booster aft skirt. An external bracket modification to the aft skirt provides a comparison basis for examining the details of the probabilistic analysis and its contributions to the design process. Also, analysis findings are compared with measured Space Shuttle flight data.

  11. Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy

    PubMed Central

    Barhoumi, Aoune; Halas, Naomi J.

    2013-01-01

    Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics. PMID:24427449

  12. Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy.

    PubMed

    Barhoumi, Aoune; Halas, Naomi J

    2011-12-15

    Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics.

  13. Effects of wing modification on an aircraft's aerodynamic parameters as determined from flight data

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1986-01-01

    A study of the effects of four wing-leading-edge modifications on a general aviation aircraft's stability and control parameters is presented. Flight data from the basic aircraft configuration and configurations with wing modifications are analyzed to determine each wing geometry's stability and control parameters. The parameter estimates and aerodynamic model forms are obtained using the stepwise regression and maximum likelihood techniques. The resulting parameter estimates and aerodynamic models are verified using vortex-lattice theory and by analysis of each model's ability to predict aircraft behavior. Comparisons of the stability and control derivative estimates from the basic wing and the four leading-edge modifications are accomplished so that the effects of each modification on aircraft stability and control derivatives can be determined.

  14. Factors affecting caregivers' ability to make environmental modifications.

    PubMed

    Messecar, D C

    2000-12-01

    This study explored factors that family caregivers described as affecting their ability to use environmental modifications. Intensive interviews and participant observation were used to collect detailed data from 24 primary family caregivers. Several factors that affect the caregivers' ability to implement modification strategies were identified in the analysis. These factors included attributes of the elderly individual, attributes of the modification, quality of the caregiver-elderly relationship, caregivers' skills, personal resources of the caregiver, and the informal and formal supports available. Of these factors, the most important were the salient skills that caregivers need to implement environmental modifications. These findings point to the importance of caregivers receiving skills training in this important dimension of caregiving. Intervention should be based on a collaborative approach that ensures the caregiver and care receiver's needs and preferences are respected.

  15. The Effect of Land Use Change on Transformation of Relief and Modification of Soils in Undulating Loess Area of East Poland

    PubMed Central

    Rejman, Jerzy; Rafalska-Przysucha, Anna; Rodzik, Jan

    2014-01-01

    The change of primary forest areas into arable land involves the transformation of relief and modification of soils. In this study, we hypothesized that relatively flat loess area was largely transformed after the change of land use due to erosion. The modifications in soil pedons and distribution of soil properties were studied after 185 years of arable land use. Structure of pedons and solum depth were measured in 128 and soil texture and soil organic carbon in 39 points. Results showed that soils of noneroded and eroded profiles occupied 14 and 50%, respectively, and depositional soils 36% of the area. As a consequence, the clay, silt, and SOC concentration varied greatly in the plowed layer and subsoil. The reconstructed profiles of eroded soils and depositional soils without the accumulation were used to develop the map of past relief. The average inclination of slopes decreased from 4.3 to 2.2°, and slopes >5° vanished in the present topography. Total erosion was 23.8 Mg ha−1 year−1. From that amount, 88% was deposited within the study area, and 12% was removed outside. The study confirmed the hypothesis of the significant effect of the land use change on relief and soils in loess areas. PMID:25614883

  16. LFC leading edge glove flight: Aircraft modification design, test article development and systems integration

    NASA Technical Reports Server (NTRS)

    Etchberger, F. R.

    1983-01-01

    Reduction of skin friction drag by suction of boundary layer air to maintain laminar flow has been known since Prandtl's published work in 1904. The dramatic increases in fuel costs and the potential for periods of limited fuel availability provided the impetus to explore technologies to reduce transport aircraft fuel consumption. NASA sponsored the Aircraft Energy Efficiency (ACEE) program in 1976 to develop technologies to improve fuel efficiency. This report documents the Lockheed-Georgia Company accomplishments in designing and fabricating a leading-edge flight test article incorporating boundary layer suction slots to be flown by NASA on their modified JetStar aircraft. Lockheed-Georgia Company performed as the integration contractor to design the JetStar aircraft modification to accept both a Lockheed and a McDonnell Douglas flight test article. McDonnell Douglas uses a porous skin concept. The report describes aerodynamic analyses, fabrication techniques, JetStar modifications, instrumentation requirements, and structural analyses and testing for the Lockheed test article. NASA will flight test the two LFC leading-edge test articles in a simulated commercial environment over a 6 to 8 month period in 1984. The objective of the flight test program is to evaluate the effectiveness of LFC leading-edge systems in reducing skin friction drag and consequently improving fuel efficiency.

  17. Toward the rational design of macrolide antibiotics to combat resistance

    DOE PAGES

    Pavlova, Anna; Parks, Jerry M.; Oyelere, Adegboyega K.; ...

    2017-04-17

    Here, macrolides, one of the most prescribed classes of antibiotics, bind in the bacterial ribosome's polypeptide exit tunnel and inhibit translation. However, mutations and other ribosomal modifications, especially to the base A2058 of the 23S rRNA, have led to a growing resistance problem. Here, we have used molecular dynamics simulations to study the macrolides erythromycin and azithromycin in wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli ribosomes. We find that the ribosomal modifications result in less favorable interactions between the base 2058 and the desosamine sugar of the macrolides, as well as greater displacement of the macrolides from theirmore » crystal structure position, illuminating the causes of resistance. We have also examined four azithromycin derivatives containing aromatic indole-analog moieties, which were previously designed based on simulations of the stalling peptide SecM in the ribosome. Surprisingly, we found that the studied moieties could adopt very different geometries when interacting with a key base in the tunnel, A751, possibly explaining their distinct activities. Based on our simulations, we propose modifications to the indole-analog moieties that should increase their interactions with A751 and, consequently, enhance the potency of future azithromycin derivatives.« less

  18. Do pH and flavonoids influence hypochlorous acid-induced catalase inhibition and heme modification?

    PubMed

    Krych-Madej, Justyna; Gebicka, Lidia

    2015-09-01

    Hypochlorous acid (HOCl), highly reactive oxidizing and chlorinating species, is formed in the immune response to invading pathogens by the reaction of hydrogen peroxide with chloride catalyzed by the enzyme myeloperoxidase. Catalase, an important antioxidant enzyme, catalyzing decomposition of hydrogen peroxide to water and molecular oxygen, hampers in vitro HOCl formation, but is also one of the main targets for HOCl. In this work we have investigated HOCl-induced catalase inhibition at different pH, and the influence of flavonoids (catechin, epigallocatechin gallate and quercetin) on this process. It has been shown that HOCl-induced catalase inhibition is independent on pH in the range 6.0-7.4. Preincubation of catalase with epigallocatechin gallate and quercetin before HOCl treatment enhances the degree of catalase inhibition, whereas catechin does not affect this process. Our rapid kinetic measurements of absorption changes around the heme group have revealed that heme modification by HOCl is mainly due to secondary, intramolecular processes. The presence of flavonoids, which reduce active catalase intermediate, Compound I to inactive Compound II have not influenced the kinetics of HOCl-induced heme modification. Possible mechanisms of the reaction of hypochlorous acid with catalase are proposed and the biological consequences are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Epigenetic Mechanisms in Developmental Alcohol-Induced Neurobehavioral Deficits

    PubMed Central

    Basavarajappa, Balapal S.; Subbanna, Shivakumar

    2016-01-01

    Alcohol consumption during pregnancy and its damaging consequences on the developing infant brain are significant public health, social, and economic issues. The major distinctive features of prenatal alcohol exposure in humans are cognitive and behavioral dysfunction due to damage to the central nervous system (CNS), which results in a continuum of disarray that is collectively called fetal alcohol spectrum disorder (FASD). Many rodent models have been developed to understand the mechanisms of and to reproduce the human FASD phenotypes. These animal FASD studies have provided several molecular pathways that are likely responsible for the neurobehavioral abnormalities that are associated with prenatal alcohol exposure of the developing CNS. Recently, many laboratories have identified several immediate, as well as long-lasting, epigenetic modifications of DNA methylation, DNA-associated histone proteins and microRNA (miRNA) biogenesis by using a variety of epigenetic approaches in rodent FASD models. Because DNA methylation patterns, DNA-associated histone protein modifications and miRNA-regulated gene expression are crucial for synaptic plasticity and learning and memory, they can therefore offer an answer to many of the neurobehavioral abnormalities that are found in FASD. In this review, we briefly discuss the current literature of DNA methylation, DNA-associated histone proteins modification and miRNA and review recent developments concerning epigenetic changes in FASD. PMID:27070644

  20. Effect of high pressure homogenization on the structure and the interfacial and emulsifying properties of β-lactoglobulin.

    PubMed

    Ali, Ali; Le Potier, Isabelle; Huang, Nicolas; Rosilio, Véronique; Cheron, Monique; Faivre, Vincent; Turbica, Isabelle; Agnely, Florence; Mekhloufi, Ghozlene

    2018-02-15

    The effect of high pressure homogenization (HPH) on the structure of β-lactoglobulin (β-lg) was studied by combining spectroscopic, chromatographic, and electrophoretic methods. The consequences of the resulting structure modifications on oil/water (O/W) interfacial properties were also assessed. Moderated HPH treatment (100 MPa/4 cycles) showed no significant modification of protein structure and interfacial properties. However, a harsher HPH treatment (300 MPa/5 cycles) induced structural transformation, mainly from β-sheets to random coils, wide loss in lipocalin core, and protein aggregation via intermolecular disulfide bridges. HPH-modified β-lg displayed higher surface hydrophobicity leading to a faster adsorption rate at the interface and an earlier formation of an elastic interfacial film at C β-lg  = 0.1 wt%. However, no modification of the interfacial properties was observed at C β-lg  = 1 wt%. At this protein concentration, the prior denaturation of β-lg by HPH did not modify the droplet size of nanoemulsions prepared with these β-lg solutions as the aqueous phases. A slightly increased creaming rate was however observed. The effects of HPH and heat denaturations appeared qualitatively similar, but with differences in their extent. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners

    PubMed Central

    Yu, Seok-Ho; Boyce, Michael; Wands, Amberlyn M.; Bond, Michelle R.; Bertozzi, Carolyn R.; Kohler, Jennifer J.

    2012-01-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modification remain poorly defined. Here we develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification in cells. We engineered mammalian cells to produce diazirine-modified O-GlcNAc by expressing a mutant form of UDP-GlcNAc pyrophosphorylase and subsequently culturing these cells with a cell-permeable, diazirine-modified form of GlcNAc-1-phosphate. Irradiation of cells with UV light activated the crosslinker, resulting in formation of covalent bonds between O-GlcNAc-modified proteins and neighboring molecules, which could be identified by mass spectrometry. We used this method to identify interaction partners for the O-GlcNAc-modified FG-repeat nucleoporins. We observed crosslinking between FG-repeat nucleoporins and nuclear transport factors, suggesting that O-GlcNAc residues are intimately associated with essential recognition events in nuclear transport. Further, we propose that the method reported here could find widespread use in investigating the functional consequences of O-GlcNAcylation. PMID:22411826

  2. Structural and functional consequences of antigenic modulation of red blood cells with methoxypoly(ethylene glycol).

    PubMed

    Murad, K L; Mahany, K L; Brugnara, C; Kuypers, F A; Eaton, J W; Scott, M D

    1999-03-15

    We previously showed that the covalent modification of the red blood cell (RBC) surface with methoxypoly(ethylene glycol) [mPEG; MW approximately 5 kD] could significantly attenuate the immunologic recognition of surface antigens. However, to make these antigenically silent RBC a clinically viable option, the mPEG-modified RBC must maintain normal cellular structure and functions. To this end, mPEG-derivatization was found to have no significant detrimental effects on RBC structure or function at concentrations that effectively blocked antigenic recognition of a variety of RBC antigens. Importantly, RBC lysis, morphology, and hemoglobin oxidation state were unaffected by mPEG-modification. Furthermore, as shown by functional studies of Band 3, a major site of modification, PEG-binding does not affect protein function, as evidenced by normal SO4- flux. Similarly, Na+ and K+ homeostasis were unaffected. The functional aspects of the mPEG-modified RBC were also maintained, as evidenced by normal oxygen binding and cellular deformability. Perhaps most importantly, mPEG-derivatized mouse RBC showed normal in vivo survival ( approximately 50 days) with no sensitization after repeated transfusions. These data further support the hypothesis that the covalent attachment of nonimmunogenic materials (eg, mPEG) to intact RBC may have significant application in transfusion medicine, especially for the chronically transfused and/or allosensitized patient.

  3. Toward the rational design of macrolide antibiotics to combat resistance

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

    Pavlova, Anna; Parks, Jerry M.; Oyelere, Adegboyega K.

    Here, macrolides, one of the most prescribed classes of antibiotics, bind in the bacterial ribosome's polypeptide exit tunnel and inhibit translation. However, mutations and other ribosomal modifications, especially to the base A2058 of the 23S rRNA, have led to a growing resistance problem. Here, we have used molecular dynamics simulations to study the macrolides erythromycin and azithromycin in wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli ribosomes. We find that the ribosomal modifications result in less favorable interactions between the base 2058 and the desosamine sugar of the macrolides, as well as greater displacement of the macrolides from theirmore » crystal structure position, illuminating the causes of resistance. We have also examined four azithromycin derivatives containing aromatic indole-analog moieties, which were previously designed based on simulations of the stalling peptide SecM in the ribosome. Surprisingly, we found that the studied moieties could adopt very different geometries when interacting with a key base in the tunnel, A751, possibly explaining their distinct activities. Based on our simulations, we propose modifications to the indole-analog moieties that should increase their interactions with A751 and, consequently, enhance the potency of future azithromycin derivatives.« less

  4. Understanding context in knowledge translation: a concept analysis study protocol.

    PubMed

    Squires, Janet E; Graham, Ian D; Hutchinson, Alison M; Linklater, Stefanie; Brehaut, Jamie C; Curran, Janet; Ivers, Noah; Lavis, John N; Michie, Susan; Sales, Anne E; Fiander, Michelle; Fenton, Shannon; Noseworthy, Thomas; Vine, Jocelyn; Grimshaw, Jeremy M

    2015-05-01

    To conduct a concept analysis of clinical practice contexts (work environments) that facilitate or militate against the uptake of research evidence by healthcare professionals in clinical practice. This will involve developing a clear definition of context by describing its features, domains and defining characteristics. The context where clinical care is delivered influences that care. While research shows that context is important to knowledge translation (implementation), we lack conceptual clarity on what is context, which contextual factors probably modify the effect of knowledge translation interventions (and hence should be considered when designing interventions) and which contextual factors themselves could be targeted as part of a knowledge translation intervention (context modification). Concept analysis. The Walker and Avant concept analysis method, comprised of eight systematic steps, will be used: (1) concept selection; (2) determination of aims; (3) identification of uses of context; (4) determination of defining attributes of context; (5) identification/construction of a model case of context; (6) identification/construction of additional cases of context; (7) identification/construction of antecedents and consequences of context; and (8) definition of empirical referents of context. This study is funded by the Canadian Institutes of Health Research (January 2014). This study will result in a much needed framework of context for knowledge translation, which identifies specific elements that, if assessed and used to tailor knowledge translation activities, will result in increased research use by nurses and other healthcare professionals in clinical practice, ultimately leading to better patient care. © 2014 John Wiley & Sons Ltd.

  5. Genetic analysis of the heparan modification network in Caenorhabditis elegans.

    PubMed

    Townley, Robert A; Bülow, Hannes E

    2011-05-13

    Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans.

  6. Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients.

    PubMed

    Zelber-Sagi, Shira; Bord, Shiran; Dror-Lavi, Gali; Smith, Matthew Lee; Towne, Samuel D; Buch, Assaf; Webb, Muriel; Yeshua, Hanny; Nimer, Assy; Shibolet, Oren

    2017-03-14

    To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient's disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients' illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits. The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants (57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding (β = 0.26; P = 0.002) and self-efficacy (β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation (β = 0.55; P < 0.001), which was related with lower self-efficacy (β = -0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy (β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat (percent of saturated fat calories from total calories) (r = -0.28, P = 0.010) and positively with fiber (r = 0.22, P = 0.047) and vitamin C intake (r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level (r = 0.34, P = 0.046). Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients.

  7. Handling Qualities Flight Testing of the Stratospheric Observatory for Infrared Astronomy (SOFIA)

    NASA Technical Reports Server (NTRS)

    Glaser, Scott T.; Strovers, Brian K.

    2011-01-01

    Airborne infrared astronomy has a long successful history, albeit relatively unknown outside of the astronomy community. A major problem with ground based infrared astronomy is the absorption and scatter of infrared energy by water in the atmosphere. Observing the universe from above 40,000 ft puts the observation platform above 99% of the water vapor in the atmosphere, thereby addressing this problem at a fraction of the cost of space based systems. The Stratospheric Observatory For Infrared Astronomy (SOFIA) aircraft is the most ambitious foray into the field of airborne infrared astronomy in history. Using a 747SP (The Boeing Company, Chicago, Illinois) aircraft modified with a 2.5m telescope located in the aft section of the fuselage, the SOFIA endeavors to provide views of the universe never before possible and at a fraction of the cost of space based systems. The modification to the airplane includes moveable doors and aperture that expose the telescope assembly. The telescope assembly is aimed and stabilized using a multitude of on board systems. This modification has the potential to cause aerodynamic anomalies that could induce undesired forces either at the cavity itself or indirectly due to interference with the empennage, both of which could cause handling qualities issues. As a result, an extensive analysis and flight test program was conducted from December 2009 through March 2011. Several methods, including a Lower Order Equivalent Systems analysis and pilot assessment, were used to ascertain the effects of the modification. The SOFIA modification was found to cause no adverse handling qualities effects and the aircraft was cleared for operational use. This paper discusses the history and modification to the aircraft, development of test procedures and analysis, results of testing and analysis, lessons learned for future projects and justification for operational certification.

  8. Epigenetics and child abuse: Modern-day Darwinism--The miraculous ability of the human genome to adapt, and then adapt again.

    PubMed

    Gershon, Naomi B; High, Pamela C

    2015-12-01

    It has long been recognized that early adversity can have life-long consequences, and the extent to which this is true is gaining increasing attention. A growing body of literature implicates Adverse Childhood Experiences, including physical, sexual, and emotional abuse, in a broad range of negative health consequences including adult psychopathology, cardiovascular, and immune disease. Increasing evidence from animal, clinical, and epidemiological studies highlight the critical role of epigenetic programing, such as DNA methylation and histone modification, in altering gene expression, brain structure and function, and ultimately life-course trajectories. This review outlines our developing insight into the interplay between our human biology and our changing environment, and explores the growing evidence base for how interventions may prevent and ameliorate damage inflicted by toxic stress in early life. © 2015 Wiley Periodicals, Inc.

  9. Neuroendocrine Consequences of Androgen Excess in Female Rodents

    PubMed Central

    Foecking, Eileen M.; McDevitt, Melissa A.; Acosta-Martínez, Maricedes; Horton, Teresa H.; Levine, Jon E.

    2008-01-01

    Androgens exert significant organizational and activational effects on the nervous system and behavior. Despite the fact that female mammals generally produce low levels of androgens, relative to the male of the same species, increasing evidence suggests that androgens can exert profound effects on the normal physiology and behavior of females during fetal, neonatal, and adult stages of life. This review examines the effects of exposure to androgens at three stages of development – as an adult, during early postnatal life and as a fetus, on reproductive hormone secretions in female rats. We examine the effects of androgen exposure both as a model of neuroendocrine sexual differentiation and with respect to the role androgens play in the normal female. We then discuss the hypothesis that androgens may cause epigenetic modification of estrogen target genes in the brain. Finally we consider the clinical consequences of excess androgen exposure in women. PMID:18374922

  10. Introduction: Obesity and reproduction.

    PubMed

    Meldrum, David R

    2017-04-01

    Women bear the predominant burden of our obesogenic environment, with a higher incidence of obesity than men, more impact on their fertility and success with treatment, and significant maternal and perinatal morbidity and mortality. In this series, the causes, consequences, and solutions regarding the obesity pandemic, the mechanisms of the effect of obesity on the female and male, the epigenetic consequences of male obesity, the marked effects on perinatal outcomes, and the effects of weight loss before conception and during pregnancy are explored. Lifestyle modifications, in particular a healthy diet and exercise during the 3-6 months before conception and during treatment, should result in better outcomes than requiring weight loss before fertility treatments. Such fundamental changes toward a healthier lifestyle will achieve steady and sustainable weight loss and long-term benefits for general health. The role of bariatric surgery before pregnancy requires careful consideration. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Instability in interacting dark sector: an appropriate holographic Ricci dark energy model

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

    Herrera, Ramón; Hipólito-Ricaldi, W.S.; Videla, Nelson, E-mail: ramon.herrera@pucv.cl, E-mail: wiliam.ricaldi@ufes.br, E-mail: nelson.videla@ing.uchile.cl

    In this paper we investigate the consequences of phantom crossing considering the perturbative dynamics in models with interaction in their dark sector. By mean of a general study of gauge-invariant variables in comoving gauge, we relate the sources of instabilities in the structure formation process with the phantom crossing. In order to illustrate these relations and its consequences in more detail, we consider a specific case of an holographic dark energy interacting with dark matter. We find that in spite of the model is in excellent agreement with observational data at background level, however it is plagued of instabilities inmore » its perturbative dynamics. We reconstruct the model in order to avoid these undesirable instabilities, and we show that this implies a modification of the concordance model at background. Also we find drastic changes on the parameters space in our model when instabilities are avoided.« less

  12. Impact of methamphetamine on infection and immunity

    PubMed Central

    Salamanca, Sergio A.; Sorrentino, Edra E.; Nosanchuk, Joshua D.; Martinez, Luis R.

    2015-01-01

    The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation. PMID:25628526

  13. 40 CFR 68.165 - Offsite consequence analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Offsite consequence analysis. 68.165 Section 68.165 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.165 Offsite consequence...

  14. 40 CFR 68.165 - Offsite consequence analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Offsite consequence analysis. 68.165 Section 68.165 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.165 Offsite consequence...

  15. 40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

  16. 40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

  17. 40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

  18. 40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

  19. 40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

  20. POLLUTION BALANCE METHOD AND THE DEMONSTRATION OF ITS APPLICATION TO MINIMIZING WASTE IN A BIOCHEMICAL PROCESS

    EPA Science Inventory

    In this study, we introduced several modifications to the WAR (waste reduction) algorithm developed earlier. These modifications were made for systematically handling sensitivity analysis and various tasks of waste minimization. A design hierarchy was formulated to promote appro...

  1. Public perceptions of hurricane modification.

    PubMed

    Klima, Kelly; Bruine de Bruin, Wändi; Morgan, M Granger; Grossmann, Iris

    2012-07-01

    If hurricane modification were to become a feasible strategy for potentially reducing hurricane damages, it would likely generate public discourse about whether to support its implementation. To facilitate an informed and constructive discourse, policymakers need to understand how people perceive hurricane modification. Here, we examine Florida residents' perceptions of hurricane modification techniques that aim to alter path and wind speed. Following the mental models approach, we conducted a survey study about public perceptions of hurricane modification that was guided by formative interviews on the topic. We report a set of four primary findings. First, hurricane modification was perceived as a relatively ineffective strategy for damage reduction, compared to other strategies for damage reduction. Second, hurricane modification was expected to lead to changes in projected hurricane path, but not necessarily to the successful reduction of projected hurricane strength. Third, more anger was evoked when a hurricane was described as having changed from the initially forecasted path or strength after an attempted modification. Fourth, unlike what we expected, participants who more strongly agreed with statements that recognized the uncertainty inherent in forecasts reported more rather than less anger at scientists across hurricane modification scenarios. If the efficacy of intensity-reduction techniques can be increased, people may be willing to support hurricane modification. However, such an effort would need to be combined with open and honest communications to members of the general public. © 2011 Society for Risk Analysis.

  2. Understanding and changing human behaviour--antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour.

    PubMed

    Stålsby Lundborg, Cecilia; Tamhankar, Ashok J

    2014-05-01

    This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the 'stages of change model', including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to 'global good', so-called 'social marketing', to improve 'welfare of the individual and society' is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement 'antibiotic mainstreaming' as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society.

  3. Potential Air Pollutant Emissions and Permitting Classifications for Two Biorefinery Process Designs in the United States

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

    Eberle, Annika; Bhatt, Arpit; Zhang, Yimin

    Advanced biofuel production facilities (biorefineries), such as those envisioned by the United States (U.S.) Renewable Fuel Standard and U.S. Department of Energy's research and development programs, often lack historical air pollutant emissions data, which can pose challenges for obtaining air emission permits that are required for construction and operation. To help fill this knowledge gap, we perform a thorough regulatory analysis and use engineering process designs to assess the applicability of federal air regulations and quantify air pollutant emissions for two feasibility-level biorefinery designs. We find that without additional emission-control technologies both biorefineries would likely be required to obtain majormore » source permits under the Clean Air Act's New Source Review program. The permitting classification (so-called 'major' or 'minor') has implications for the time and effort required for permitting and therefore affects the cost of capital and the fuel selling price. Consequently, we explore additional technically feasible emission-control technologies and process modifications that have the potential to reduce emissions to achieve a minor source permitting classification. Finally, our analysis of air pollutant emissions and controls can assist biorefinery developers with the air permitting process and inform regulatory agencies about potential permitting pathways for novel biorefinery designs.« less

  4. Educational interventions in childhood obesity: a systematic review with meta-analysis of randomized clinical trials.

    PubMed

    Sbruzzi, Graciele; Eibel, Bruna; Barbiero, Sandra M; Petkowicz, Rosemary O; Ribeiro, Rodrigo A; Cesa, Claudia C; Martins, Carla C; Marobin, Roberta; Schaan, Camila W; Souza, Willian B; Schaan, Beatriz D; Pellanda, Lucia C

    2013-05-01

    To assess the effectiveness of educational interventions including behavioral modification, nutrition and physical activity to prevent or treat childhood obesity through a systematic review and meta-analysis of randomized trials. A search of databases (PubMed, EMBASE and Cochrane CENTRAL) and references of published studies (from inception until May 2012) was conducted. Eligible studies were randomized trials enrolling children 6 to 12 years old and assessing the impact of educational interventions during 6 months or longer on waist circumference, body mass index (BMI), blood pressure and lipid profile to prevent or treat childhood obesity. Calculations were performed using a random effects method and pooled-effect estimates were obtained using the final values. Of 22.852 articles retrieved, 26 trials (23.617 participants) were included. There were no differences in outcomes assessed in prevention studies. However, in treatment studies, educational interventions were associated with a significant reduction in waist circumference [-3.21 cm (95%CI -6.34, -0.07)], BMI [-0.86 kg/m(2) (95%CI -1.59, -0.14)] and diastolic blood pressure [-3.68 mmHg (95%CI -5.48, -1.88)]. Educational interventions are effective in treatment, but not prevention, of childhood obesity and its consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. A Comparison of Descriptive and Functional Analyses of Inappropriate Mealtime Behavior.

    PubMed

    Borrero, Carrie S W; England, Jennie D; Sarcia, Ben; Woods, Julia N

    2016-12-01

    In recent years, rather than being used to assess the potential function of a response, descriptive assessment methods have been applied to evaluate potential consequences or contingencies for problem behavior (Borrero, Woods, Borrero, Masler, & Lesser in Journal of Applied Behavior Analysis, 43 , 71-88. doi: 10.1901/jaba.2010.43-71, 2010) or to assist with designing baseline conditions to approximate caregiver behavior (Casey et al. in Behavior Modification, 33 , 537-558. doi: 10.1177/0145445509341457, 2009). It has been shown that descriptive assessments of some forms of problem behavior (e.g., self-injury, aggression) are not good indicators of behavioral function and should not be used exclusively when conducting functional behavior assessments (Thompson & Iwata in Journal of Applied Behavior Analysis, 40 , 333-338. doi: 10.1901/jaba.2007.56.06/epdf, 2007). However, the extent to which descriptive assessments of inappropriate mealtime behavior can predict behavioral function is not yet clear. We conducted descriptive assessments of inappropriate mealtime behavior and compared the results to functional analyses for ten children with severe food refusal. Results showed that, for 71 % of participants, the descriptive and functional analyses matched. These results suggest that the correspondence between descriptive and functional analyses, at least for inappropriate mealtime behavior, may be higher than that for other forms of problem behavior.

  6. Potential Air Pollutant Emissions and Permitting Classifications for Two Biorefinery Process Designs in the United States

    DOE PAGES

    Eberle, Annika; Bhatt, Arpit; Zhang, Yimin; ...

    2017-04-26

    Advanced biofuel production facilities (biorefineries), such as those envisioned by the United States (U.S.) Renewable Fuel Standard and U.S. Department of Energy's research and development programs, often lack historical air pollutant emissions data, which can pose challenges for obtaining air emission permits that are required for construction and operation. To help fill this knowledge gap, we perform a thorough regulatory analysis and use engineering process designs to assess the applicability of federal air regulations and quantify air pollutant emissions for two feasibility-level biorefinery designs. We find that without additional emission-control technologies both biorefineries would likely be required to obtain majormore » source permits under the Clean Air Act's New Source Review program. The permitting classification (so-called 'major' or 'minor') has implications for the time and effort required for permitting and therefore affects the cost of capital and the fuel selling price. Consequently, we explore additional technically feasible emission-control technologies and process modifications that have the potential to reduce emissions to achieve a minor source permitting classification. Finally, our analysis of air pollutant emissions and controls can assist biorefinery developers with the air permitting process and inform regulatory agencies about potential permitting pathways for novel biorefinery designs.« less

  7. Potential Air Pollutant Emissions and Permitting Classifications for Two Biorefinery Process Designs in the United States.

    PubMed

    Eberle, Annika; Bhatt, Arpit; Zhang, Yimin; Heath, Garvin

    2017-06-06

    Advanced biofuel production facilities (biorefineries), such as those envisioned by the United States (U.S.) Renewable Fuel Standard and U.S. Department of Energy's research and development programs, often lack historical air pollutant emissions data, which can pose challenges for obtaining air emission permits that are required for construction and operation. To help fill this knowledge gap, we perform a thorough regulatory analysis and use engineering process designs to assess the applicability of federal air regulations and quantify air pollutant emissions for two feasibility-level biorefinery designs. We find that without additional emission-control technologies both biorefineries would likely be required to obtain major source permits under the Clean Air Act's New Source Review program. The permitting classification (so-called "major" or "minor") has implications for the time and effort required for permitting and therefore affects the cost of capital and the fuel selling price. Consequently, we explore additional technically feasible emission-control technologies and process modifications that have the potential to reduce emissions to achieve a minor source permitting classification. Our analysis of air pollutant emissions and controls can assist biorefinery developers with the air permitting process and inform regulatory agencies about potential permitting pathways for novel biorefinery designs.

  8. Analysis of good practices, barriers and drivers for ELTs pyrolysis industrial application.

    PubMed

    Zabaniotou, A; Antoniou, N; Bruton, G

    2014-11-01

    Boosting of eco-innovative solutions for End of Life Tyres (ELTs) management, under the principles of the EU Resource Efficiency Roadmap and the Waste Framework Directive, can not only diminish the environmental hazards and the consequent societal cost, but also result to the establishment of a novel perception regarding ELTs; thus, a valuable stock of resources that can be exploited. Despite the extensive scientific research of the previous years on ELTs depolymerisation via pyrolysis highlighting its eco-innovative characteristics, the use of pyrolysis to process scrap tyres has not yet achieved a broad commercial success, with economic viability and product standardization to constitute the primary impediments. More specifically, pyrolysis was not applied to an extensive industrial scale so far, due to deficient market analysis, legislative barriers, economic instability and sometimes public acceptance. All the above issues are addressed by the present study. Modifications on current EU legislation can prevent or reduce delays or derailment of efforts on pyrolysis, through its differentiation from incineration. The attainment of economic viability could be realized through the valorization of the pyrolytic char towards activated carbon production for environmental depollution applications; needless to say, the penetration on niche and well-organised markets is more than essential. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Neutron observables from inclusive lepton scattering on nuclei

    NASA Astrophysics Data System (ADS)

    Rinat, A. S.; Taragin, M. F.

    2010-07-01

    We analyze new data from Thomas Jefferson National Accelerator Facility (JLab) for inclusive electron scattering on various targets. Computed and measured total inclusive cross sections in the range 0.3≲x≲0.95 show reasonable agreement on a logarithmic scale for all targets. However, closer inspection of the quasielastic components reveals serious discrepancies. European Muon Collaboration (EMC) ratios with conceivably smaller systematic errors fare the same. As a consequence, the new data do not enable the extraction of the magnetic form factor GMn and the structure function F2n of the neutron, although the application of exactly the same analysis to older data had been successful. We incorporate in the above analysis older CLAS Collaboration data on F22H. Removal of some scattered points from those makes it appear possible to obtain the desired neutron information. We compare our results with others from alternative sources. Special attention is paid to the A=3 isodoublet cross sections and EMC ratios. Present data exist only for He3, but the available input in combination with charge symmetry enables computations for H3. Their average is the computed isoscalar part and is compared with the empirical modification of He3 EMC ratios toward a fictitious A=3 isosinglet.

  10. A proposal for the experimental detection of CSL induced random walk

    PubMed Central

    Bera, Sayantani; Motwani, Bhawna; Singh, Tejinder P.; Ulbricht, Hendrik

    2015-01-01

    Continuous Spontaneous Localization (CSL) is one possible explanation for dynamically induced collapse of the wave-function during a quantum measurement. The collapse is mediated by a stochastic non-linear modification of the Schrödinger equation. A consequence of the CSL mechanism is an extremely tiny violation of energy-momentum conservation, which can, in principle, be detected in the laboratory via the random diffusion of a particle induced by the stochastic collapse mechanism. In a paper in 2003, Collett and Pearle investigated the translational CSL diffusion of a sphere, and the rotational CSL diffusion of a disc, and showed that this effect dominates over the ambient environmental noise at low temperatures and extremely low pressures (about ten-thousandth of a pico-Torr). In the present paper, we revisit their analysis and argue that this stringent condition on pressure can be relaxed, and that the CSL effect can be seen at the pressure of about a pico-Torr. A similar analysis is provided for diffusion produced by gravity-induced decoherence, where the effect is typically much weaker than CSL. We also discuss the CSL induced random displacement of a quantum oscillator. Lastly, we propose possible experimental set-ups justifying that CSL diffusion is indeed measurable with the current technology. PMID:25563619

  11. Black string corrections in variable tension braneworld scenarios

    NASA Astrophysics Data System (ADS)

    Da Rocha, Roldão; Hoff da Silva, J. M.

    2012-02-01

    Braneworld models with variable tension are investigated, and the corrections on the black string horizon along the extra dimension are provided. Such corrections are encrypted in additional terms involving the covariant derivatives of the variable tension on the brane, providing profound consequences concerning the black string horizon variation along the extra dimension, near the brane. The black string horizon behavior is shown to be drastically modified by the terms corrected by the brane variable tension. In particular, a model motivated by the phenomenological interesting case regarding Eötvös branes is investigated. It forthwith provides further physical features regarding variable tension braneworld scenarios, heretofore concealed in all previous analysis in the literature. All precedent analysis considered uniquely the expansion of the metric up to the second order along the extra dimension, which is able to evince solely the brane variable tension absolute value. Notwithstanding, the expansion terms aftermath, further accomplished in this paper from the third order on, elicits the successive covariant derivatives of the brane variable tension, and their respective coupling with the extrinsic curvature, the Weyl tensor, and the Riemann and Ricci tensors, as well as the scalar curvature. Such additional terms are shown to provide sudden modifications in the black string horizon in a variable tension braneworld scenario.

  12. Detection of ground motions using high-rate GPS time-series

    NASA Astrophysics Data System (ADS)

    Psimoulis, Panos A.; Houlié, Nicolas; Habboub, Mohammed; Michel, Clotaire; Rothacher, Markus

    2018-05-01

    Monitoring surface deformation in real-time help at planning and protecting infrastructures and populations, manage sensitive production (i.e. SEVESO-type) and mitigate long-term consequences of modifications implemented. We present RT-SHAKE, an algorithm developed to detect ground motions associated with landslides, sub-surface collapses, subsidences, earthquakes or rock falls. RT-SHAKE detects first transient changes in individual GPS time series before investigating for spatial correlation(s) of observations made at neighbouring GPS sites and eventually issue a motion warning. In order to assess our algorithm on fast (seconds to minute), large (from 1 cm to meters) and spatially consistent surface motions, we use the 1 Hz GEONET GNSS network data of the Tohoku-Oki MW9.0 2011 as a test scenario. We show the delay of detection of seismic wave arrival by GPS records is of ˜10 seconds with respect to an identical analysis based on strong-motion data and this time delay depends on the level of the time-variable noise. Nevertheless, based on the analysis of the GPS network noise level and ground motion stochastic model, we show that RT-SHAKE can narrow the range of earthquake magnitude, by setting a lower threshold of detected earthquakes to MW6.5-7, if associated with a real-time automatic earthquake location system.

  13. Beyond 'knock-out' mice: new perspectives for the programmed modification of the mammalian genome.

    PubMed

    Cohen-Tannoudji, M; Babinet, C

    1998-10-01

    The emergence of gene inactivation by homologous recombination methodology in embryonic stem cells has revolutionized the field of mouse genetics. Indeed, the availability of a rapidly growing number of mouse null mutants has represented an invaluable source of knowledge on mammalian development, cellular biology and physiology and has provided many models for human inherited diseases. In recent years, improvements of the original 'knock-out' strategy, as well as the exploitation of exogenous enzymatic systems that are active in the recombination process, have considerably extended the range of genetic manipulations that can be produced. For example, it is now possible to create a mouse bearing a targeted point mutation as the unique change in its entire genome therefore allowing very fine dissection of gene function in vivo. Chromosome alterations such as large deletions, inversions or translocations can also be designed and will facilitate the global functional analysis of the mouse genome. This will extend the possibilities of creating models of human pathologies that frequently originate from various chromosomal disorders. Finally, the advent of methods allowing conditional gene targeting will open the way for the analysis of the consequence of a particular mutation in a defined organ and at a specific time during the life of a mouse.

  14. Influence of linear profile modification and loading conditions on the dynamic tooth load and stress of high contact ratio gears

    NASA Technical Reports Server (NTRS)

    Lee, Chinwai; Lin, Hsiang Hsi; Oswald, Fred B.; Townsend, Dennis P.

    1990-01-01

    A computer simulation for the dynamic response of high-contact-ratio spur gear transmissions is presented. High contact ratio gears have the potential to produce lower dynamic tooth loads and minimum root stress but they can be sensitive to tooth profile errors. The analysis presented examines various profile modifications under realistic loading conditions. The effect of these modifications on the dynamic load (force) between mating gear teeth and the dynamic root stress is presented. Since the contact stress is dependent on the dynamic load, minimizing dynamic loads will also minimize contact stresses. It is shown that the combination of profile modification and the applied load (torque) carried by a gear system has a significant influence on gear dynamics. The ideal modification at one value of applied load will not be the best solution for a different load. High-contact-ratio gears were found to require less modification than standard low-contact-ratio gears. High-contact-ratio gears are more adversely affected by excess modification than by under modification. In addition, the optimal profile modification required to minimize the dynamic load (hence the contact stress) on a gear tooth differs from the optimal modification required to minimize the dynamic root (bending) stress. Computer simulation can help find the design tradeoffs to determine the best profile modification to satisfy the conflicting constraints of minimizing both the load and root stress in gears which must operate over a range of applied loads.

  15. Detecting peroxiredoxin hyperoxidation by one-dimensional isoelectric focusing.

    PubMed

    Cao, Zhenbo; Bulleid, Neil J

    The activity of typical 2-cys peroxiredoxin (Prxs) can be regulated by hyperoxidation with a consequent loss of redox activity. Here we developed a simple assay to monitor the level of hyperoxidation of different typical 2-cys prxs simultaneously. This assay only requires standard equipment and can compare different samples on the same gel. It requires much less time than conventional 2D gels and gives more information than Western blotting with an antibody specific for hyperoxidized peroxiredoxin. This method could also be used to monitor protein modification with a charge difference such as phosphorylation.

  16. Landforms and Landform Evolution in West Germany: International Conference on Geomorphology (2nd) Held in Frankfurt am Main on 3-9 September 1989. CATENA Supplement 15

    DTIC Science & Technology

    1989-01-01

    and their subsequent modification by non -glacial processes. In the Central Uplands north of the rivers Main and Nahe’ W Andres directs attention to the...terraces. In the South German Scarplands,A+i: Bremer focuses on the role of structural and climatic controls in the long-term evolution of cuestas and...eastwards rainfall. The natural or quasi -natural to the Frankenwald in the northeast of vegetation is dense. Consequently, Bavaria. present-day

  17. Further Examination of the Thermodynamic Modification of the Inflow Layer of Tropical Cyclones by Vertical Wind Shear

    DTIC Science & Technology

    2013-01-11

    Q. J. Roy. Meteor. Soc., in review, 2012. Srivastava , R . C.: A model of intense downdrafts driven by the melt- ing and evaporation of precipitation, J...formation and intensity of downdrafts ( Srivastava , 1987). 5A brief discussion of the potential consequences of the envi- ronmental wind profile can be found...the time series is shown. (b) As in (a) but for RMN68 (da k r d), 10RMN68 (light red), ICE68 (dark grey), and 10ICE68 (light grey). Note that the tilt

  18. A user interface for a knowledge-based planning and scheduling system

    NASA Technical Reports Server (NTRS)

    Mulvehill, Alice M.

    1988-01-01

    The objective of EMPRESS (Expert Mission Planning and Replanning Scheduling System) is to support the planning and scheduling required to prepare science and application payloads for flight aboard the US Space Shuttle. EMPRESS was designed and implemented in Zetalisp on a 3600 series Symbolics Lisp machine. Initially, EMPRESS was built as a concept demonstration system. The system has since been modified and expanded to ensure that the data have integrity. Issues underlying the design and development of the EMPRESS-I interface, results from a system usability assessment, and consequent modifications are described.

  19. Labrets in Africa and Amazonia: medical implications and cultural determinants.

    PubMed

    Garve, Roland; Garve, Miriam; Türp, Jens C; Meyer, Christian G

    2017-02-01

    The custom of wearing labrets has a long tradition. Labrets appeared independently several thousand years ago in various culture groups in Asia, Europe, Africa and the Americas. Today, apart from diverse body modifications as increasingly practiced in western civilisations, lip plates and plugs are found among a small number of tribal groups only in Africa and Amazonia. We summarise the history of labrets in different societies, describe medical consequences of wearing lip plates and plugs for jaws and teeth and address relevant cultural issues. © 2016 John Wiley & Sons Ltd.

  20. Transcript Isoform Variation Associated with Cytosine Modification in Human Lymphoblastoid Cell Lines.

    PubMed

    Zhang, Xu; Zhang, Wei

    2016-06-01

    Cytosine modification on DNA is variable among individuals, which could correlate with gene expression variation. The effect of cytosine modification on interindividual transcript isoform variation (TIV), however, remains unclear. In this study, we assessed the extent of cytosine modification-specific TIV in lymphoblastoid cell lines (LCLs) derived from unrelated individuals of European and African descent. Our study detected cytosine modification-specific TIVs for 17% of the analyzed genes at a 5% false discovery rate. Forty-five percent of the TIV-associated cytosine modifications correlated with the overall gene expression levels as well, with the corresponding CpG sites overrepresented in transcript initiation sites, transcription factor binding sites, and distinct histone modification peaks, suggesting that alternative isoform transcription underlies the TIVs. Our analysis also revealed 33% of the TIV-associated cytosine modifications that affected specific exons, with the corresponding CpG sites overrepresented in exon/intron junctions, splicing branching points, and transcript termination sites, implying that the TIVs are attributable to alternative splicing or transcription termination. Genetic and epigenetic regulation of TIV shared target preference but exerted independent effects on 61% of the common exon targets. Cytosine modification-specific TIVs detected from LCLs were differentially enriched in those detected from various tissues in The Cancer Genome Atlas, indicating their developmental dependency. Genes containing cytosine modification-specific TIVs were enriched in pathways of cancers and metabolic disorders. Our study demonstrated a prominent effect of cytosine modification variation on the transcript isoform spectrum over gross transcript abundance and revealed epigenetic contributions to diseases that were mediated through cytosine modification-specific TIV. Copyright © 2016 by the Genetics Society of America.

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