WorldWideScience

Sample records for activities leading to information generation

  1. Bioactive lysophospholipids generated by hepatic lipase degradation of lipoproteins lead to complement activation via the classical pathway.

    Science.gov (United States)

    Ma, Wanchao; Paik, David C; Barile, Gaetano R

    2014-09-09

    We determined bioactivity of lysophospholipids generated by degradation of the low-density (LDL), very low-density (VLDL), and high-density (HDL) lipoproteins with hepatic lipase (HL), cholesterol esterase (CE), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The LDL, VLDL, and HDL were treated with HL, CE, and Lp-PLA2 after immobilization on plates, and complement activation studies were performed with diluted human serum. Complement component 3 (C3) fixation, a marker for complement activation, was determined with a monoclonal anti-human C3d antibody. Enzymatic properties of HL and CE were assayed with triglyceride and phosphatidylcholine substrates for triglyceride hydrolase and phospholipase A activities. The ARPE-19 cells were used for viability studies. The HL degradation of human lipoproteins LDL, VLDL, or HDL results in the formation of modified lipoproteins that can activate the complement pathway. Complement activation is dose- and time-dependent upon HL and occurs via the classical pathway. Enzymatic studies suggest that the phospholipase A1 activity of HL generates complement-activating lysophospholipids. C-reactive protein (CRP), known to simultaneously interact with complement C1 and complement factor H (CFH), further enhances HL-induced complement activation. The lysophospholipids, 1-Palmitoyl-sn-glycero-3-phosphocholine and 1-Oleoyl-sn-glycero-3-phosphocholine, can be directly cytotoxic to ARPE-19 cells. The HL degradation of lipoproteins, known to accumulate in the outer retina and in drusen, can lead to the formation of bioactive lysophospholipids that can trigger complement activation and induce RPE cellular dysfunction. Given the known risk associations for age-related macular degeneration (AMD) with HL, CRP, and CFH, this study elucidates a possible damage pathway for age-related macular degeneration (AMD) in genetically predisposed individuals, that HL activity may lead to accumulation of lysophospholipids to initiate complement

  2. Rapid degradation of an active formylglycine generating enzyme variant leads to a late infantile severe form of multiple sulfatase deficiency.

    Science.gov (United States)

    Schlotawa, Lars; Radhakrishnan, Karthikeyan; Baumgartner, Matthias; Schmid, Regula; Schmidt, Bernhard; Dierks, Thomas; Gärtner, Jutta

    2013-09-01

    Multiple sulfatase deficiency (MSD) is a rare inborn error of metabolism affecting posttranslational activation of sulfatases by the formylglycine generating enzyme (FGE). Due to mutations in the encoding SUMF1 gene, FGE's catalytic capacity is impaired resulting in reduced cellular sulfatase activities. Both, FGE protein stability and residual activity determine disease severity and have previously been correlated with the clinical MSD phenotype. Here, we report a patient with a late infantile severe course of disease. The patient is compound heterozygous for two so far undescribed SUMF1 mutations, c.156delC (p.C52fsX57) and c.390A>T (p.E130D). In patient fibroblasts, mRNA of the frameshift allele is undetectable. In contrast, the allele encoding FGE-E130D is expressed. FGE-E130D correctly localizes to the endoplasmic reticulum and has a very high residual molecular activity in vitro (55% of wildtype FGE); however, it is rapidly degraded. Thus, despite substantial residual enzyme activity, protein instability determines disease severity, which highlights that potential MSD treatment approaches should target protein folding and stabilization mechanisms.

  3. Creating novel activated factor XI inhibitors through fragment based lead generation and structure aided drug design.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Activated factor XI (FXIa inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1'-S2' FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1'-S2' binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1'-S2' binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.

  4. Next-generation science information network for leading-edge applications

    Energy Technology Data Exchange (ETDEWEB)

    Urushidani, S. [National Institute of Informatics, 2-1-2 Hitotsubashi Chiyoda-ku, Tokyo 101-8430 (Japan)], E-mail: urushi@nii.ac.jp; Matsukata, J. [National Institute of Informatics, 2-1-2 Hitotsubashi Chiyoda-ku, Tokyo 101-8430 (Japan)

    2008-04-15

    High-speed networks are definitely essential tools for leading-edge applications in many research areas, including nuclear fusion research. This paper describes a number of advanced features in the Japanese next-generation science information network, called SINET3, and gives researchers clues on the uses of advanced high-speed network for their applications. The network services have four categories, multiple layer transfer, enriched virtual private network, enhanced quality-of-service, and bandwidth on demand services, and comprise a versatile service platform. The paper also describes the network architecture and advanced networking capabilities that enable economical service accommodation and flexible network resource assignment as well as effective use of Japan's first 40-Gbps lines.

  5. Active Listening Improve Your Ability to Listen and Lead

    CERN Document Server

    (CCL), Center for Creative Leadership

    2011-01-01

    Active listening is a person's willingness and ability to hear and understand. At its core, active listening is a state of mind that involves paying full and careful attention to the other person, avoiding premature judgment, reflecting understanding, clarifying information, summarizing, and sharing. By learning and committing to the skills and behaviors of active listening, leaders can become more effective listeners and, over time, improve their ability to lead.

  6. Leading Generation Y

    National Research Council Canada - National Science Library

    Newman, Jill M

    2008-01-01

    .... Whether referred to as the Millennial Generation, Generation Y or the Next Generation, the Army needs to consider the gap between Boomers, Generation X and the Soldiers that fill our junior ranks...

  7. Stem cells from human exfoliated deciduous tooth exhibit stromal-derived inducing activity and lead to generation of neural crest cells from human embryonic stem cells.

    Science.gov (United States)

    Karbalaie, Khadijeh; Tanhaei, Somayyeh; Rabiei, Farzaneh; Kiani-Esfahani, Abbas; Masoudi, Najmeh Sadat; Nasr-Esfahani, Mohammad Hossein; Baharvand, Hossein

    2015-01-01

    The neural crest is a transient structure of early vertebrate embryos that generates neural crest cells (NCCs). These cells can migrate throughout the body and produce a diverse array of mature tissue types. Due to the ethical and technical problems surrounding the isolation of these early human embryo cells, researchers have focused on in vitro studies to produce NCCs and increase their knowledge of neural crest development. In this experimental study, we cultured human embryonic stem cells (hESCs) on stromal stem cells from human exfoliated deciduous teeth (SHED) for a two-week period. We used different approaches to characterize these differentiated cells as neural precursor cells (NPCs) and NCCs. In the first co-culture week, hESCs appeared as crater-like structures with marginal rosettes. NPCs derived from these structures expressed the early neural crest marker p75 in addition to numerous other genes associated with neural crest induction such as SNAIL, SLUG, PTX3 and SOX9. Flow cytometry analysis showed 70% of the cells were AP2/P75 positive. Moreover, the cells were able to self-renew, sustain multipotent differentiation potential, and readily form neurospheres in suspension culture. SHED, as an adult stem cell with a neural crest origin, has stromal-derived inducing activity (SDIA) and can be used as an NCC inducer from hESCs. These cells provide an invaluable resource to study neural crest differentiation in both normal and disordered human neural crest development.

  8. 75 FR 66087 - Agency Information Collection Activities; Proposed Collection; Comment Request; Residential Lead...

    Science.gov (United States)

    2010-10-27

    ... Information Collection Activities; Proposed Collection; Comment Request; Residential Lead-Based Paint Hazard... Office of Management and Budget (OMB). This ICR, entitled: ``Residential Lead-Based Paint Hazard... other technological collection techniques or other forms of information technology, e.g., permitting...

  9. 77 FR 65414 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Lead in...

    Science.gov (United States)

    2012-10-26

    ... monitor exposure to lead, provide medical surveillance, train employees about the hazards of lead, and..., mechanical, or other technological collection techniques or other forms of information technology, e.g...

  10. 77 FR 65415 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Lead in...

    Science.gov (United States)

    2012-10-26

    .... Employers must monitor exposure to lead, provide medical surveillance, train employees about the hazards of..., electronic, mechanical, or other technological collection techniques or other forms of information technology...

  11. A Simplified 3D Model of Whole Heart Electrical Activity and 12-Lead ECG Generation

    Directory of Open Access Journals (Sweden)

    Siniša Sovilj

    2013-01-01

    Full Text Available We present a computationally efficient three-dimensional bidomain model of torso-embedded whole heart electrical activity, with spontaneous initiation of activation in the sinoatrial node, incorporating a specialized conduction system with heterogeneous action potential morphologies throughout the heart. The simplified geometry incorporates the whole heart as a volume source, with heart cavities, lungs, and torso as passive volume conductors. We placed four surface electrodes at the limbs of the torso: , , and and six electrodes on the chest to simulate the Einthoven, Goldberger-augmented and precordial leads of a standard 12-lead system. By placing additional seven electrodes at the appropriate torso positions, we were also able to calculate the vectorcardiogram of the Frank lead system. Themodel was able to simulate realistic electrocardiogram (ECG morphologies for the 12 standard leads, orthogonal , , and leads, as well as the vectorcardiogram under normal and pathological heart states. Thus, simplified and easy replicable 3D cardiac bidomain model offers a compromise between computational load and model complexity and can be used as an investigative tool to adjust cell, tissue, and whole heart properties, such as setting ischemic lesions or regions of myocardial infarction, to readily investigate their effects on whole ECG morphology.

  12. Optimization of lead (ii) ions adsorption on to chemically activated ...

    African Journals Online (AJOL)

    The adsorption of Lead (II) ion on to chemically activated carbon has been studied and optimized in a batch reactor system. The zinc chloride impregnated sugarcane bagasse was thermal activated in a fixed bed reactor in the presence of argon gas. The surface morphology, surface functional group and thermal stability ...

  13. Who Avoids Cancer Information? Examining a Psychological Process Leading to Cancer Information Avoidance.

    Science.gov (United States)

    Chae, Jiyoung

    2016-07-01

    Although cancer information avoidance (CIA) is detrimental to public health, predictors of CIA have not been fully investigated. Based on uncertainty management theory, this study viewed CIA as a response to uncertainty related to the distress associated with cancer information and illustrated the psychological process leading to CIA. Given the current information context, it was hypothesized that cancer information overload (CIO), accompanied by confusion and stress about cancer information, causes CIA. As trait anxiety is a strong predictor of CIO, it was also hypothesized that trait anxiety has an indirect effect on CIA through CIO. Study 1 tested this relationship in a U.S. sample (N = 384); the results showed that CIO was positively associated with CIA and that trait anxiety indirectly influenced CIA through CIO. Whereas Study 1 tested the relationship with cross-sectional data in the general cancer context, Study 2 replicated Study 1 with 3-wave longitudinal data in the context of a specific cancer (i.e., stomach cancer) in South Korea (N = 1,130 at Wave 1, 813 at Wave 2, and 582 at Wave 3). Trait anxiety at Wave 1 predicted CIO at Wave 2, which in turn increased CIA at Wave 3, suggesting that some people are inherently inclined to avoid cancer information due to their trait anxiety, which results in confusion about cancer information.

  14. Red light generation through the lead boro-telluro-phosphate glasses activated by Eu3+ ions

    Science.gov (United States)

    Selvi, S.; Marimuthu, K.; Suriya Murthy, N.; Muralidharan, G.

    2016-09-01

    Lead boro-telluro-phosphate glasses containing 0.05 to 2.0 wt% of Eu3+ ions were prepared through melt quenching technique. Structural characteristics of title glasses were identified through XRD, FTIR and Raman studies. The optical properties of the prepared glasses were studied using UV-Vis-NIR absorption and photoluminescence spectra. From the resultant spectra, we have obtained the bonding parameters (δ), nephelauxetic ratio (β), direct and indirect band gaps and Urbach energy (ΔE) values. A deep red luminescence due to 5D0 → 7F2 transition of Eu3+ ions could be observed for the title glasses. The local site symmetry around the Eu3+ ions and the degree of Eu3+-O2- covalence were assessed from the luminescence intensity ratio of 5D0 → 7F2/5D0 → 7F1 transitions. Judd-Ofelt intensity parameters, calculated from the luminescence spectra, were used to estimate the radiative parameters like transition probability (A), branching ratio (βexp, βcal) and stimulated emission cross-section (σPE) concerning the 5D0 → 7FJ (J = 0, 1, 2, 3 and 4) transitions. The important laser parameters, gain bandwidth and optical gain are also estimated. The decay curves associated with the transition from 5D0 state was found to be single-exponential at all Eu3+ ion concentrations. CIE colour coordinates and colour purity of the prepared glasses were estimated from the CIE chromaticity diagram.

  15. Activity-based analyses lead to better decision making.

    Science.gov (United States)

    Player, S

    1998-08-01

    Activity-based costing (ABC) and activity-based management (ABM) are cost-management tools that are relatively new to the healthcare industry. ABC is used for strategic decision making. It assesses the costs associated with specific activities and resources and links those costs to specific internal and external customers of the healthcare enterprise (e.g., patients, service lines, and physician groups) to determine the costs associated with each customer. This cost information then can be adjusted to account for anticipated changes and to predict future costs. ABM, on the other hand, supports operations by focusing on the causes of costs and how costs can be reduced. It assesses cost drivers that directly affect the cost of a product or service, and uses performance measures to evaluate the financial or nonfinancial benefit an activity provides. By identifying each cost driver and assessing the value the element adds to the healthcare enterprise, ABM provides a basis for selecting areas that can be changed to reduce costs.

  16. Factors that lead Generation Y nurses to consider or reject nurse leader roles

    Directory of Open Access Journals (Sweden)

    Rose O. Sherman

    Full Text Available Objective: This study examined factors that lead Generation Y nurses to consider or reject nursing leadership roles. Background: Almost half of the current nurse leaders in the country are expected to retire by the end of the decade. Generation Y will soon comprise 50% of the nursing workforce and organizations look to them to assume leadership roles. Learning how to effectively recruit, motivate and retain Generation Y nurse leaders will be critical to the future of nursing. Methods: This was a qualitative study that used a ConCensus™ process approach to collect the themes and factors of importance to participants related to nursing leadership roles. Three focus groups were conducted during 2013 and 2014 with 32 Generation Y Registered Nurses, not currently in leadership positions and born on or after January 1st, 1981. Key findings: Feedback from current nurse leaders about their roles is primarily negative. The strongest incentive for Generation Y nurses to seek leadership roles is the potential to create meaningful change in healthcare. Fear of failure in the role and lack of work-life balance are significant deterrents to accepting a leadership role. Conclusions: Generation Y nurses do see the value and importance of nursing leadership in making a difference in patient care but have concerns about the level of support that will be available to them as they assume these roles. Attention must be directed toward providing resources and strategies to develop skilled Generation Y nurse leaders in order to promote effective succession planning. Keywords: Generation Y, Millennials, Nursing leadership, Succession planning

  17. Using a geographic information system to improve childhood lead-screening efforts.

    Science.gov (United States)

    Graff, Robert

    2013-06-13

    The Idaho Division of Public Health conducted a pilot study to produce a lead-exposure-risk map to help local and state agencies better target childhood lead-screening efforts. Priority lead-screening areas, at the block group level, were created by using county tax assessor data and geographic information system software. A series of maps were produced, indicating childhood lead-screening prevalence in areas in which there was high potential for exposure to lead. These maps could enable development of more systematically targeted and cost-effective childhood lead-screening efforts.

  18. Portals to Wonderland: health portals lead to confusing information about the effects of health care.

    Science.gov (United States)

    Glenton, Claire; Paulsen, Elizabeth J; Oxman, Andrew D

    2005-03-15

    The Internet offers a seemingly endless amount of health information of varying quality. Health portals, which provide entry points to quality-controlled collections of websites, have been hailed as a solution to this problem. The objective of this study is to assess the extent to which government-run health portals provide access to relevant, valid and understandable information about the effects of health care. We selected eight clinically relevant questions for which there was a systematic review, searched four portals for answers, and compared the answers we found to the results of the systematic reviews. Our searches resulted in 3400 hits, 155 of which mentioned both the condition and the intervention in one of the eight questions. Sixty-three of the 155 web pages did not give any information about the effect of the intervention. Seventy-seven qualitatively described the effects of the intervention. Twenty-six of these had information that was too unclear to be categorised; 15 were not consistent with the systematic review; and 36 were consistent with the review, but usually did not mention what happens without the intervention, what outcomes have been measured or when they were measured. Fifteen web pages quantitatively described effects. Four of these were abstracts from the systematic review, nine had information that was incomplete and potentially misleading because of a lack of information about people not receiving the intervention and the length of follow-up; one had information that was consistent with the review, but only referred to three trials whereas the review included six; and one was consistent with the review. Information accessible through health portals is unlikely to be based on systematic reviews and is often unclear, incomplete and misleading. Portals are only as good as the websites they lead to. Investments in national health portals are unlikely to benefit consumers without investments in the production and maintenance of relevant

  19. Portals to Wonderland: Health portals lead to confusing information about the effects of health care

    Directory of Open Access Journals (Sweden)

    Oxman Andrew D

    2005-03-01

    Full Text Available Abstract Background The Internet offers a seemingly endless amount of health information of varying quality. Health portals, which provide entry points to quality-controlled collections of websites, have been hailed as a solution to this problem. The objective of this study is to assess the extent to which government-run health portals provide access to relevant, valid and understandable information about the effects of health care. Methods We selected eight clinically relevant questions for which there was a systematic review, searched four portals for answers, and compared the answers we found to the results of the systematic reviews. Results Our searches resulted in 3400 hits, 155 of which mentioned both the condition and the intervention in one of the eight questions. Sixty-three of the 155 web pages did not give any information about the effect of the intervention. Seventy-seven qualitatively described the effects of the intervention. Twenty-six of these had information that was too unclear to be categorised; 15 were not consistent with the systematic review; and 36 were consistent with the review, but usually did not mention what happens without the intervention, what outcomes have been measured or when they were measured. Fifteen web pages quantitatively described effects. Four of these were abstracts from the systematic review, nine had information that was incomplete and potentially misleading because of a lack of information about people not receiving the intervention and the length of follow-up; one had information that was consistent with the review, but only referred to three trials whereas the review included six; and one was consistent with the review. Conclusion Information accessible through health portals is unlikely to be based on systematic reviews and is often unclear, incomplete and misleading. Portals are only as good as the websites they lead to. Investments in national health portals are unlikely to benefit consumers

  20. CONTRIBUTION OF CHLIDREN'S ACTIVITIES TO LEAD CONTAMINATION OF FOOD

    Science.gov (United States)

    This study evaluates the relationship of children's hygiene habits and food handling behaviors on lead levels on hands and handled foods for toddlers living in lead contaminated homes. Forty eight inner city toddlers who had previously been identified as having elevated blood le...

  1. WAX ActiveLibrary: a tool to manage information overload.

    Science.gov (United States)

    Hanka, R; O'Brien, C; Heathfield, H; Buchan, I E

    1999-11-01

    WAX Active-Library (Cambridge Centre for Clinical Informatics) is a knowledge management system that seeks to support doctors' decision making through the provision of electronic books containing a wide range of clinical knowledge and locally based information. WAX has been piloted in several regions in the United Kingdom and formally evaluated in 17 GP surgeries based in Cambridgeshire. The evaluation has provided evidence that WAX Active-Library significantly improves GPs' access to relevant information sources and by increasing appropriate patient management and referrals this might also lead to an improvement in clinical outcomes.

  2. Next generation information systems

    Energy Technology Data Exchange (ETDEWEB)

    Limback, Nathan P [Los Alamos National Laboratory; Medina, Melanie A [Los Alamos National Laboratory; Silva, Michelle E [Los Alamos National Laboratory

    2010-01-01

    The Information Systems Analysis and Development (ISAD) Team of the Safeguards Systems Group at Los Alamos National Laboratory (LANL) has been developing web based information and knowledge management systems for sixteen years. Our vision is to rapidly and cost effectively provide knowledge management solutions in the form of interactive information systems that help customers organize, archive, post and retrieve nonproliferation and safeguards knowledge and information vital to their success. The team has developed several comprehensive information systems that assist users in the betterment and growth of their organizations and programs. Through our information systems, users are able to streamline operations, increase productivity, and share and access information from diverse geographic locations. The ISAD team is also producing interactive visual models. Interactive visual models provide many benefits to customers beyond the scope of traditional full-scale modeling. We have the ability to simulate a vision that a customer may propose, without the time constraints of traditional engineering modeling tools. Our interactive visual models can be used to access specialized training areas, controlled areas, and highly radioactive areas, as well as review site-specific training for complex facilities, and asset management. Like the information systems that the ISAD team develops, these models can be shared and accessed from any location with access to the internet. The purpose of this paper is to elaborate on the capabilities of information systems and interactive visual models as well as consider the possibility of combining the two capabilities to provide the next generation of infonnation systems. The collection, processing, and integration of data in new ways can contribute to the security of the nation by providing indicators and information for timely action to decrease the traditional and new nuclear threats. Modeling and simulation tied to comprehensive

  3. Meditation leads to reduced default mode network activity beyond an active task.

    Science.gov (United States)

    Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2015-09-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.

  4. Structural distortions due to missense mutations in human formylglycine-generating enzyme leading to multiple sulfatase deficiency.

    Science.gov (United States)

    Meshach Paul, D; Chadah, Tania; Senthilkumar, B; Sethumadhavan, Rao; Rajasekaran, R

    2017-11-03

    The major candidate for multiple sulfatase deficiency is a defective formylglycine-generating enzyme (FGE). Though adequately produced, mutations in FGE stall the activation of sulfatases and prevent their activity. Missense mutations, viz. E130D, S155P, A177P, W179S, C218Y, R224W, N259I, P266L, A279V, C336R, R345C, A348P, R349Q and R349W associated with multiple sulfatase deficiency are yet to be computationally studied. Aforementioned mutants were initially screened through ws-SNPs&GO 3D program. Mutant R345C acquired the highest score, and hence was studied in detail. Discrete molecular dynamics explored structural distortions due to amino acid substitution. Therein, comparative analyses of wild type and mutant were carried out. Changes in structural contours were observed between wild type and mutant. Mutant had low conformational fluctuation, high atomic mobility and more compactness than wild type. Moreover, free energy landscape showed mutant to vary in terms of its conformational space as compared to wild type. Subsequently, wild type and mutant were subjected to single-model analyses. Mutant had lesser intra molecular interactions than wild type suggesting variations pertaining to its secondary structure. Furthermore, simulated thermal denaturation showed dissimilar pattern of hydrogen bond dilution. Effects of these variations were observed as changes in elements of secondary structure. Docking studies of mutant revealed less favourable binding energy towards its substrate as compared to wild type. Therefore, theoretical explanations for structural distortions of mutant R345C leading to multiple sulfatase deficiency were revealed. The protocol of the study could be useful to examine the effectiveness of pharmacological chaperones prior to experimental studies.

  5. Information-theoretic approach to lead-lag effect on financial markets

    Science.gov (United States)

    Fiedor, Paweł

    2014-08-01

    Recently the interest of researchers has shifted from the analysis of synchronous relationships of financial instruments to the analysis of more meaningful asynchronous relationships. Both types of analysis are concentrated mostly on Pearson's correlation coefficient and consequently intraday lead-lag relationships (where one of the variables in a pair is time-lagged) are also associated with them. Under the Efficient-Market Hypothesis such relationships are not possible as all information is embedded in the prices, but in real markets we find such dependencies. In this paper we analyse lead-lag relationships of financial instruments and extend known methodology by using mutual information instead of Pearson's correlation coefficient. Mutual information is not only a more general measure, sensitive to non-linear dependencies, but also can lead to a simpler procedure of statistical validation of links between financial instruments. We analyse lagged relationships using New York Stock Exchange 100 data not only on an intraday level, but also for daily stock returns, which have usually been ignored.

  6. Innovated application of mechanical activation to separate lead from scrap cathode ray tube funnel glass.

    Science.gov (United States)

    Yuan, Wenyi; Li, Jinhui; Zhang, Qiwu; Saito, Fumio

    2012-04-03

    The disposal of scrap cathode ray tube (CRT) funnel glass has become a global environmental problem due to the rapid shrinkage of new CRT monitor demand, which greatly reduces the reuse for remanufacturing. To detoxificate CRT funnel glass by lead recovery with traditional metallurgical methods, mechanical activation by ball milling was introduced to pretreat the funnel glass. As a result, substantial physicochemical changes have been observed after mechanical activation including chemical breakage and defects formation in glass inner structure. These changes contribute to the easy dissolution of the activated sample in solution. High yield of 92.5% of lead from activated CRT funnel glass by diluted nitric acid leaching and successful formation of lead sulfide by sulfur sulfidization in water have also been achieved. All the results indicate that the application of mechanical activation on recovering lead from CRT funnel glass is efficient and promising, which is also probably appropriate to detoxificate any other kind of leaded glass.

  7. Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

    Directory of Open Access Journals (Sweden)

    Koshiro Nishimoto

    2016-01-01

    Full Text Available Background. The immunohistochemical detection of aldosterone synthase (CYP11B2 and steroid 11β-hydroxylase (CYP11B1 has enabled the identification of aldosterone-producing cell clusters (APCCs in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, % and the number of APCCs (NOA, APCCs/mm2 were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG and zona fasciculata (ZF without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

  8. Missing information caused by death leads to bias in relative risk estimates.

    Science.gov (United States)

    Binder, Nadine; Schumacher, Martin

    2014-10-01

    In most clinical and epidemiologic studies, information on disease status is usually collected at regular follow-up visits. Often, this information can only be retrieved in individuals who are alive at follow-up, and studies frequently right censor individuals with missing information because of death in the analysis. Such ad hoc analyses can lead to seriously biased hazard ratio estimates of potential risk factors. We systematically investigate this bias. We illustrate under which conditions the bias can occur. Considering three numerical studies, we characterize the bias, its magnitude, and direction as well as its real-world relevance. Depending on the situation studied, the bias can be substantial and in both directions. It is mainly caused by differential mortality: if deaths without occurrence of the disease are more pronounced, the risk factor effect is overestimated. However, if the risk for dying after being diseased is prevailing, the effect is mostly underestimated and might even change signs. The bias is a result of both, a too coarse follow-up and an ad hoc Cox analysis in which the data sample is restricted to the observed and known event history. This is especially relevant for studies in which a considerable number of death cases are expected. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. The Agent of extracting Internet Information with Lead Order

    Science.gov (United States)

    Mo, Zan; Huang, Chuliang; Liu, Aijun

    In order to carry out e-commerce better, advanced technologies to access business information are in need urgently. An agent is described to deal with the problems of extracting internet information that caused by the non-standard and skimble-scamble structure of Chinese websites. The agent designed includes three modules which respond to the process of extracting information separately. A method of HTTP tree and a kind of Lead algorithm is proposed to generate a lead order, with which the required web can be retrieved easily. How to transform the extracted information structuralized with natural language is also discussed.

  10. Social exclusion leads to attentional bias to emotional social information: Evidence from eye movement.

    Science.gov (United States)

    Chen, Zhuohao; Du, Jinchen; Xiang, Min; Zhang, Yan; Zhang, Shuyue

    2017-01-01

    Social exclusion has many effects on individuals, including the increased need to belong and elevated sensitivity to social information. Using a self-reporting method, and an eye-tracking technique, this study explored people's need to belong and attentional bias towards the socio-emotional information (pictures of positive and negative facial expressions compared to those of emotionally-neutral expressions) after experiencing a brief episode of social exclusion. We found that: (1) socially-excluded individuals reported higher negative emotions, lower positive emotions, and stronger need to belong than those who were not socially excluded; (2) compared to a control condition, social exclusion caused a longer response time to probe dots after viewing positive or negative face images; (3) social exclusion resulted in a higher frequency ratio of first attentional fixation on both positive and negative emotional facial pictures (but not on the neutral pictures) than the control condition; (4) in the social exclusion condition, participants showed shorter first fixation latency and longer first fixation duration to positive pictures than neutral ones but this effect was not observed for negative pictures; (5) participants who experienced social exclusion also showed longer gazing duration on the positive pictures than those who did not; although group differences also existed for the negative pictures, the gaze duration bias from both groups showed no difference from chance. This study demonstrated the emotional response to social exclusion as well as characterising multiple eye-movement indicators of attentional bias after experiencing social exclusion.

  11. Active Generations: An Intergenerational Approach to Preventing Childhood Obesity

    Science.gov (United States)

    Werner, Danilea; Teufel, James; Holtgrave, Peter L.; Brown, Stephen L.

    2012-01-01

    Background: Over the last 3 decades, US obesity rates have increased dramatically as more children and more adults become obese. This study explores an innovative program, Active Generations, an intergenerational nutrition education and activity program implemented in out-of-school environments (after school and summer camps). It utilizes older…

  12. Information Technology How Leading Firms Use It to Gain an Advantage

    CERN Document Server

    Rapp, William V

    2002-01-01

    Focuses on the strategic principles fundamental to using information technology to gain market control. This book provides case examples of how to use IT. It is designed to help managers struggling with how to harness the information revolution. It describes how non-information technology companies are employing strategic principles and using it.

  13. Open Government Leads To The Abolition Of The Right To The Informational Privacy: An Invitation To Discussion

    Directory of Open Access Journals (Sweden)

    Tetiana Korshun

    2017-12-01

    Full Text Available The main thesis of the article is that informational privacy slows down the progress in many areas of science and social development. Current tendencies to open government lead us to construct a fully transparent society. And we should be ready to organize our public and private life in the absence of the informational privacy, including the most sensible areas. This transformation will influence almost every sphere of our social life. Increasing the level of tolerance, more security for private businesses, cost savings for states and individuals, the new wave in the development of the electronic services from governments and corporations, more incentives for law-changing process, the next level of social trust are the core of the transparent society after the abolition of the right to the informational privacy. But there are many more consequences that require further detailed study and research.

  14. What if ethical buying behavior leads to boycotts? : The buying behavior of Generation Z

    OpenAIRE

    Helmersson, Filip; Svensson, Amanda

    2016-01-01

    The care for the environment has been a hot topic during the last fifteen years. Ecological and Fairtrade products made from sustainable materials and methods can be found in almost every store. It seems like awareness regarding our environmental impact has increased and therefore changed our purchase behavior. The awareness has also created pressure on the companies to behave in an ethical manner, if the consumers feel that their ethical needs are not acknowledged, they will tend to stop pur...

  15. Framework for Research Leading to Improved Assessment of Dredge Generated Plumes

    Science.gov (United States)

    2004-07-01

    Borrowman ERDC WES 601-634-4048 Thomas.D.Borrowman@erdc.usace.army.mil Ray Bergeron Cable Arm 734-676-6108 info@cablearm.com David Templeton Anchor ...251-0450 mhammaker@aem- inc.com Steve Cappellino Anchor Env. LLC 949-833-7150 scappelino@anchorenv.com Ryan Barth Anchor Env. LLC 206-287-9130 rbarth...feeding epifauna, for example sponges. Coral and kelp forest communities are also susceptible to increased sedimentation rates ( Selby and Ooms, 1996

  16. Using Informational and Narrative Picture Walks to Promote Student-Generated Questions

    Science.gov (United States)

    Ness, Molly

    2017-01-01

    The purpose of this article is to explore the use of picture walks in narrative and informational text as a method to encourage question generation. This article overviews the instructional benefits of having students generate their own questions before, during, and after reading. Featured are two classrooms where students pose questions through…

  17. How Does Information Spread on Social Media Lead to Effective Change?

    Science.gov (United States)

    Varghese, Thomas K

    2017-09-01

    Social media encompasses computer-mediated technologies that facilitate the creation and sharing of information, ideas, and other forms of expression via virtual communities and networks. The key, of course, is the ability and willingness for information to be shared. But why does some information spread on social media and not others? What factors translate social media awareness to action? In this article, we explore these themes using case studies, as well as tips on how you can utilize social media to effectively champion a cause.

  18. Multiple signaling pathways leading to the activation of interferon regulatory factor 3.

    Science.gov (United States)

    Servant, Marc J; Grandvaux, Nathalie; Hiscott, John

    2002-09-01

    Virus infection of susceptible cells activates multiple signaling pathways that orchestrate the activation of genes, such as cytokines, involved in the antiviral and innate immune response. Among the kinases induced are the mitogen-activated protein (MAP) kinases, Jun-amino terminal kinases (JNK) and p38, the IkappaB kinase (IKK) and DNA-PK. In addition, virus infection also activates an uncharacterized VAK responsible for the C-terminal phosphorylation and subsequent activation of interferon regulatory factor 3 (IRF-3). Virus-mediated activation of IRF-3 through VAK is dependent on viral entry and transcription, since replication deficient virus failed to induce IRF-3 activity. The pathways leading to VAK activation are not well characterized, but IRF-3 appears to represent a novel cellular detection pathway that recognizes viral nucleocapsid (N) structure. Recently, the range of inducers responsible for IRF-3 activation has increased. In addition to virus infection, recognition of bacterial infection mediated through lipopolysaccharide by Toll-like receptor 4 has also been reported. Furthermore, MAP kinase kinase kinase (MAP KKK)-related pathways and DNA-PK induce N-terminal phosphorylation of IRF-3. This review summarizes recent observations in the identification of novel signaling pathways leading to IRF-3 activation.

  19. Variation in behavioral engagement during an active learning activity leads to differential knowledge gains in college students.

    Science.gov (United States)

    LaDage, Lara D; Tornello, Samantha L; Vallejera, Jennilyn M; Baker, Emily E; Yan, Yue; Chowdhury, Anik

    2018-03-01

    There are many pedagogical techniques used by educators in higher education; however, some techniques and activities have been shown to be more beneficial to student learning than others. Research has demonstrated that active learning and learning in which students cognitively engage with the material in a multitude of ways result in better understanding and retention. The aim of the present study was to determine which of three pedagogical techniques led to improvement in learning and retention in undergraduate college students. Subjects partook in one of three different types of pedagogical engagement: hands-on learning with a model, observing someone else manipulate the model, and traditional lecture-based presentation. Students were then asked to take an online quiz that tested their knowledge of the new material, both immediately after learning the material and 2 wk later. Students who engaged in direct manipulation of the model scored higher on the assessment immediately after learning the material compared with the other two groups. However, there were no differences among the three groups when assessed after a 2-wk retention interval. Thus active learning techniques that involve direct interaction with the material can lead to learning benefits; however, how these techniques benefit long-term retention of the information is equivocal.

  20. Leading Generative Groups: A Conceptual Model

    Science.gov (United States)

    London, Manuel; Sobel-Lojeski, Karen A.; Reilly, Richard R.

    2012-01-01

    This article presents a conceptual model of leadership in generative groups. Generative groups have diverse team members who are expected to develop innovative solutions to complex, unstructured problems. The challenge for leaders of generative groups is to balance (a) establishing shared goals with recognizing members' vested interests, (b)…

  1. Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation

    NARCIS (Netherlands)

    Maas, Coen; Govers-Riemslag, Jos W. P.; Bouma, Barend; Schiks, Bettina; Hazenberg, Bouke P. C.; Lokhorst, Henk M.; Hammarstrom, Per; ten Cate, Hugo; de Groot, Philip G.; Bouma, Bonno N.; Gebbink, Martijn F. B. G.

    When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the

  2. Generating Embodied Information Presentations

    NARCIS (Netherlands)

    Theune, Mariet; Heylen, Dirk K.J.; Nijholt, Antinus; Stock, O.; Zancanaro, M

    2005-01-01

    The output modalities available for information presentation by embodied, human-like agents include both language and various nonverbal cues such as pointing and gesturing. These human, nonverbal modalities can be used to emphasize, extend or even replace the language output produced by the agent.

  3. Health Information Preference among Youth and Caregivers related to Second-Generation Antipsychotic Treatment.

    Science.gov (United States)

    Xu, Yan; Nguyen, Duc; Davidson, Jana; Panagiotopoulos, Constadina

    2012-11-01

    To determine the health information-seeking preferences of youth with mental health challenges and their caregivers, focusing on health literacy needs related to second-generation antipsychotics (SGAs). One hundred fifty two youth and 158 caregivers attending outpatient psychiatry clinics at BC Children's Hospital between February 2009 and December 2010 completed a SGA health literacy survey. Youth and caregivers placed emphasis on understanding the benefits and side effects of SGA-treatment, along with strategies to prevent potential side effects. While psychiatrists were viewed as a crucial source of information by both groups, pharmacists were an under-utilized resource by youth. Both youth and caregivers preferred brochures from healthcare providers, websites, and support groups to access health information; however, preferences diverged among other activities. Specifically, youth favoured practical, "hands-on" programs such as cooking and exercise classes, whereas caregivers showed greater interest in didactic presentations and conferences. Sex differences were observed in receptiveness towards certain programs and resources. The findings from this study support the inclusion of caregivers and youth of both sexes with mental health conditions in the future development of educational resources related to medications such as SGAs. Health literacy strategies need to be multi-faceted, and utilize mixed methods to ensure broad reach and applicability.

  4. Microbial electrolysis contribution to anaerobic digestion of waste activated sludge, leading to accelerated methane production

    DEFF Research Database (Denmark)

    Liu, Wenzong; Cai, Weiwei; Guo, Zechong

    2016-01-01

    Methane production rate (MPR) in waste activated sludge (WAS) digestion processes is typically limitedby the initial steps of complex organic matter degradation, leading to a limited MPR due to sludgefermentation speed of solid particles. In this study, a novel microbial electrolysis AD reactor (ME......-AD) wasused to accelerate methane production for energy recovery from WAS. Carbon bioconversion wasaccelerated by ME producing H2 at the cathode. MPR was enhanced to 91.8 gCH4/m3 reactor/d in themicrobial electrolysis ME-AD reactor, thus improving the rate by 3 times compared to control conditions (30.6 gCH4......-AD reactor allowed to significantly enhance carbon degradation and methaneproduction from WAS....

  5. Microbial electrolysis contribution to anaerobic digestion of waste activated sludge, leading to accelerated methane production

    DEFF Research Database (Denmark)

    Liu, Wenzong; Cai, Weiwei; Guo, Zechong

    2016-01-01

    Methane production rate (MPR) in waste activated sludge (WAS) digestion processes is typically limitedby the initial steps of complex organic matter degradation, leading to a limited MPR due to sludgefermentation speed of solid particles. In this study, a novel microbial electrolysis AD reactor (ME......-AD) wasused to accelerate methane production for energy recovery from WAS. Carbon bioconversion wasaccelerated by ME producing H2 at the cathode. MPR was enhanced to 91.8 gCH4/m3 reactor/d in themicrobial electrolysis ME-AD reactor, thus improving the rate by 3 times compared to control conditions (30.6 gCH4....../m3 reactor/d in AD). The methane production yield reached 116.2 mg/g VSS in the ME-ADreactor. According to balance calculation on electron transfer and methane yield, the increasedmethane production was mostly dependent on electron contribution through the ME system. Thus, theuse of the novel ME...

  6. Can pluralistic approaches based upon unknown languages enhance learner engagement and lead to active social inclusion?

    Science.gov (United States)

    Dahm, Rebecca

    2017-08-01

    One way to foster active social inclusion is to enable students to develop a positive attitude to "foreignness". Creating a situation where mainstream students are less wary of foreign languages and cultures, and where newcomers feel their linguistic background is being valued, provides favourable conditions for the inclusion of these newcomers in the classroom and in society. However, language classrooms in French schools rarely take any previously acquired linguistic knowledge into account, thus unconsciously contributing to the rift between multilingual learners (e.g. 1st- and 2nd-generation immigrant children, refugees, children of parents with different mother tongues) and French learners. Native French learners' first experience of learning another language is usually when English is added as a subject to their curriculum in primary school. In some schools in France, English lessons now include the simulation of multilingual situations, designed in particular for the French "quasi-monolingual" students to lose their fear of unknown languages and "foreignness" in general. But the overall aim is to help both groups of learners become aware of the positive impact of multilingualism on cognitive abilities. However, to achieve long-term effects, this awareness-raising needs to be accompanied by maximum engagement on the part of the students. This article explores an instructional strategy termed Pluralistic Approaches based upon Unknown Languages (PAUL), which was designed to develop learning strategies of quasi-monolingual students in particular and to increase learner engagement more generally. The results of a small-scale PAUL study discussed by the author seem to confirm an increase in learner engagement leading to an enhancement of learning outcomes. Moreover, PAUL seems indeed suitable for helping to prepare the ground for social inclusion.

  7. Introduction to the Symposium "Leading Students and Faculty to Quantitative Biology through Active Learning".

    Science.gov (United States)

    Waldrop, Lindsay D; Miller, Laura A

    2015-11-01

    The broad aim of this symposium and set of associated papers is to motivate the use of inquiry-based, active-learning teaching techniques in undergraduate quantitative biology courses. Practical information, resources, and ready-to-use classroom exercises relevant to physicists, mathematicians, biologists, and engineers are presented. These resources can be used to address the lack of preparation of college students in STEM fields entering the workforce by providing experience working on interdisciplinary and multidisciplinary problems in mathematical biology in a group setting. Such approaches can also indirectly help attract and retain under-represented students who benefit the most from "non-traditional" learning styles and strategies, including inquiry-based, collaborative, and active learning. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  8. Generating Embodied Information Presentations

    OpenAIRE

    Theune, Mariet; Heylen, Dirk K. J.; Nijholt, Antinus; Stock, O.; Zancanaro, M

    2005-01-01

    The output modalities available for information presentation by embodied, human-like agents include both language and various nonverbal cues such as pointing and gesturing. These human, nonverbal modalities can be used to emphasize, extend or even replace the language output produced by the agent. To deal with the interdependence between language and nonverbal signals, their production processes should be integrated. In this chapter, we discuss the issues involved in extending a natural langu...

  9. Simulated evolution of three-dimensional magnetic nulls leading to generation of cylindrically-shaped current sheets

    Science.gov (United States)

    Kumar, Sanjay; Bhattacharyya, R.

    2017-06-01

    The performed magnetohydrodynamic simulation examines the importance of magnetofluid evolution, which naturally leads to current sheets in the presence of three-dimensional (3D) magnetic nulls. The initial magnetic field is constructed by superposing a 3D force-free field on a constant axial magnetic field. The initial field supports 3D magnetic nulls having the classical spine axis and the dome-shaped fan surface and exerts non-zero Lorentz force on the magnetofluid. Importantly, the simulation identifies the development of current sheets near the 3D magnetic nulls. The morphology of the current sheets is similar to a cylindrical surface where the surface encloses the spine axis. The development is because of favorable deformation of magnetic field lines constituting the dome-shaped fan surface. The deformation of field lines is found to be caused by the flow generated by magnetic reconnections at current sheets which are located away from the cylindrically shaped current sheets.

  10. Information Behavior and Japanese Students: How Can an Understanding of the Research Process Lead to Better Information Literacy?

    Science.gov (United States)

    Ishimura, Yusuke

    2013-01-01

    Academic librarians are striving to better serve international students as this emerging population grows on university campuses. Past studies of international students generally focus on linguistic and cultural differences in relation to information literacy skills development. However, it is necessary to go beyond these factors to better serve…

  11. β-lactam antibiotic-induced release of lipoteichoic acid from Staphylococcus aureus leads to activation of neutrophil granulocytes

    Directory of Open Access Journals (Sweden)

    Hartung Thomas

    2006-06-01

    Full Text Available Abstract Background Polymorphonuclear neutrophil granulocytes (PMN are phagocytes of the first line of antimicrobial defense. Previously we demonstrated that lipoteichoic acid (LTA from Staphylococcus aureus (S. aureus directly activates neutrophil granulocytes. Others have reported that exposure of S. aureus to β-lactam antibiotics leads to LTA release. In the present study we addressed the question whether exposure of S. aureus to β-lactam antibiotics or antibiotics of other groups results in the generation of PMN-stimulating activity and whether this activity can be attributed to LTA. Methods S. aureus were exposed to flucloxacillin, a β-lactam antibiotic or to the protein synthesis-inhibitors erythromycin and gentamicin, or to ciprofloxacin, a gyrase inhibitor. Supernatants of the antibiotic-treated bacteria were assayed for their LTA content and for their effect on PMN functions. Results We observed that exposure of S. aureus to flucloxacillin and, to a lesser degree to ciprofloxacin, but not to erythromycin or gentamicin led to LTA release. Co-incubation of neutrophil granulocytes with LTA-containing supernatants led to PMN activation as assed by morphological changes, release of IL-8, delay of spontaneous apoptosis and enhanced phagocytic activity. Depletion of LTA from the supernatants markedly reduced their PMN-activating capacity. Conclusion The findings suggest that, via the activation of PMN, antibiotic-induced LTA release from S. aureus leads to enhanced antimicrobial activity of the innate immune defense mechanisms.

  12. Contribution of generative leisure activities to cognitive function in elderly Sri Lankan adults.

    Science.gov (United States)

    Maselko, Joanna; Sebranek, Matthew; Mun, Mirna H; Perera, Bilesha; Ahs, Jill; Ostbye, Truls

    2014-09-01

    To examine the unique contribution of generative leisure activities, defined as activities motivated by a concern for others and a need to contribute something to the next generation. Cross-sectional survey. Peri-urban and rural area in southern Sri Lanka. Community-dwelling adults aged 60 and older (N = 252). The main predictors were leisure activities, grouped into generative, social, or solitary. The main outcome was cognitive function, assessed using the Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). More-frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the effect of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured using the MoCA (β = 0.47, 95% confidence interval (CI) = 0.11-0.83) and the IQCODE (β = -0.81, 95% CI = -1.54 to -0.09). In this combined model, solitary activities were also independently associated with slower cognitive decline using the MoCA (β = 0.40, 95% CI = 0.16-0.64) but not the IQCODE (β = -0.38, 95% CI = -0.88-0.12); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully according to sex. Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline in elderly adults. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  13. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

  14. The Contribution of Generative Leisure Activities to Cognitive Function among Sri Lankan Elderly

    Science.gov (United States)

    Maselko, Joanna; Sebranek, Matthew; Mun, Mirna Hodzic; Perera, Bilesha; Ahs, Jill; Østbye, Truls

    2014-01-01

    OBJECTIVES Although a substantive body of research has shown a protective association between leisure activities and cognitive function, consistent evidence is lacking about which specific types of activities should be promoted. The objective of this analysis was to examine the unique contribution of generative leisure activities, defined as activities motivated by “a concern for others and a need to contribute something to the next generation” (Erikson). DESIGN Cross-sectional survey. SETTING Peri-urban and rural area in southern Sri Lanka. PARTICIPANTS Community dwelling adults aged 60+ (n=252). MEASUREMENTS Main predictors were leisure activities grouped into generative, social, or solitary. Main outcome was cognitive function assessed with Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS We found that more frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the impact of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured with the MoCA (β =0.47 (0.11 to 0.83) and the IQCODE (β = -0.81 (-1.54 to -0.09)). In this combined model, solitary activities were also independently associated with slower cognitive decline with the MoCA (β =0.40 (0.16, 0.64), but not with IQCODE (β =-0.38 (-0.88, 0.12)); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully by gender. CONCLUSION Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline among the elderly. PMID:25139145

  15. Generation of monoclonal antibodies to native active human glycosyltransferases

    DEFF Research Database (Denmark)

    Vester-Christensen, Malene Bech; Bennett, Eric Paul; Clausen, Henrik

    2013-01-01

    using monoclonal antibodies therefore provides an excellent strategy to analyze the glycosylation process in cells. A major drawback has been difficulties in generating antibodies to glycosyltransferases and validating their specificities. Here we describe a simple strategy for generating...... and characterizing monoclonal antibodies to human glycosyltransferases. This strategy includes a process for recombinant production and purification of enzymes for immunization, a simple selection strategy for isolation of antibodies with optimal properties for in situ detection of enzyme expression......, and a comprehensive strategy for characterizing the fine specificity of such antibodies....

  16. Reactions Between Vapor Phase Lead Compounds and In Situ Generated Silica Particles at Various Lead-Silicon Feed Ratios: Applications to Toxic Metal Capture in Combustors.

    Science.gov (United States)

    Owens, Timothy M; Biswas, Pratim

    1996-06-01

    A detailed characterization was performed of the particles produced under various Pb:Si molar feed ratios for a maximum flow reactor temperature of 1000 °C. The silica particles formed in the high temperature region coagulated and only partially coalesced to form large agglomerate structures of high specific surface area. For a lead-only feed, the resulting particles were hydrocerussite with small but detectable amounts of massicot. As the silica precursor was inlet in excess amounts (Pb:Si crystalline lead compounds disappeared and amorphous lead-silica complexes dominated. The particle morphology also changed from cylindrical, polygonal, and spherical shapes to large agglomerate structures composed of several size modes of primary particles. At Pb:Si molar feed ratios of 1:12 and 1:29, the particles making up the chainlike agglomerate structure were primarily spherical, with larger lead silicate spherical particles (=0.5 |im) attached to the agglomerate. The lead was found to be distributed throughout the large agglomerate structures, implying easier capture of lead emissions in particulate control devices.

  17. What Leads Students to Adopt Information from Wikipedia? An Empirical Investigation into the Role of Trust and Information Usefulness

    Science.gov (United States)

    Shen, Xiao-Liang; Cheung, Christy M. K.; Lee, Matthew K. O.

    2013-01-01

    With the prevalence of the Internet, it has become increasingly easy and common for students to seek information from various online sources. Wikipedia is one of the largest and most popular reference websites that university students may heavily rely on in completing their assignments and other course-related projects. Based on the information…

  18. Using the Fish Larvae and Egg Exposure System (FLEES) to Generate Effects Data for Informing Environmental Windows

    Science.gov (United States)

    2017-03-01

    Generate Effects Data for Informing Environmental Windows by Justin L. Wilkens and Burton C. Suedel PURPOSE: The Fish Larvae and Egg Exposure...response data for dredging projects where environmental windows (EW) severely restrict dredging operations (Lutz et al. 2012). This technical note...sediments from dredging activities on aquatic resources (Suedel et al. 2008). Environmental windows are most commonly established to protect

  19. Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research

    OpenAIRE

    Facio Flavia M; Sapp Julie C; Linn Amy; Biesecker Leslie G

    2012-01-01

    Abstract Background Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results. Discussion We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of...

  20. Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation

    Directory of Open Access Journals (Sweden)

    Anja B. Geldhof

    2003-01-01

    Full Text Available Several reports describe regulatory interactions between NK cells and CTLs. We addressed the issue of NK participation in the early anti-tumor defense by inoculating α-ASGM-1 treated mice with BW-Sp3 T lymphoma. Rejection of BW-Sp3 depends on strong CTL responses. Our results demonstrated that (i NK cells are a prerequisite for efficient CTL generation and (ii the absence of NK cells favors the outgrowth of alternatively activated macrophages that can suppress CTL restimulation. In vitro studies demonstrate that in splenic cultures from NK-deficient, tumor-bearing mice, the presence of alternatively activated macrophages correlates with a lack of Type 1 cytokines, while the production of Type 2 cytokines is promoted. Provision of the Type 1 cytokine, IFN-γ can boost overall CTL activity but does not revert the dominance of arginase producing adherent cells in the NK-deficient CTL cultures. The role of NK effector functions in the efficient switch of the immune system towards Type 1 activation was evaluated in cytotoxicity assays. The results indicate that the accessory function of NK can depend at least partially on their ability to preferentially engage arginase-producing cells, suggesting that NK/macrophage lytic interactions might be involved in the switch from Type 2 to Type 1-dependent immune responses.

  1. Multiple nucleophilic elbows leading to multiple active sites in a single module esterase from Sorangium cellulosum

    DEFF Research Database (Denmark)

    Udatha, D.B.R.K. Gupta; Madsen, Karina Marie; Panagiotou, Gianni

    2015-01-01

    was used to generate variants with deactivated nucleophilic elbows and the functional promiscuity was analyzed. In silico analysis together with enzymological characterization interestingly showed that each nucleophilic elbow formed a local active site with varied substrate specificities and affinities....... To our knowledge, this is the first report presenting the role of multiple nucleophilic elbows in the catalytic promiscuity of an esterase. Further structural analysis at protein unit level indicates the new evolutionary trajectories in emerging promiscuous esterases....

  2. Mixed-source reintroductions lead to outbreeding depression in second-generation descendents of a native North American fish

    Science.gov (United States)

    Huff, D.D.; Miller, L.M.; Chizinski, C.J.; Vondracek, B.

    2011-01-01

    Reintroductions are commonly employed to preserve intraspecific biodiversity in fragmented landscapes. However, reintroduced populations are frequently smaller and more geographically isolated than native populations. Mixing genetically, divergent sources are often proposed to attenuate potentially low genetic diversity in reintroduced populations that may result from small effective population sizes. However, a possible negative tradeoff for mixing sources is outbreeding depression in hybrid offspring. We examined the consequences of mixed-source reintroductions on several fitness surrogates at nine slimy sculpin (Cottus cognatus) reintroduction sites in south-east Minnesota. We inferred the relative fitness of each crosstype in the reintroduced populations by comparing their growth rate, length, weight, body condition and persistence in reintroduced populations. Pure strain descendents from a single source population persisted in a greater proportion than expected in the reintroduced populations, whereas all other crosstypes occurred in a lesser proportion. Length, weight and growth rate were lower for second-generation intra-population hybrid descendents than for pure strain and first-generation hybrids. In the predominant pure strain, young-of the-year size was significantly greater than any other crosstype. Our results suggested that differences in fitness surrogates among crosstypes were consistent with disrupted co-adapted gene complexes associated with beneficial adaptations in these reintroduced populations. Future reintroductions may be improved by evaluating the potential for local adaptation in source populations or by avoiding the use of mixed sources by default when information on local adaptations or other genetic characteristics is lacking. ?? 2011 Blackwell Publishing Ltd.

  3. A Study of Personality Traits to Explain Employees' Information Security Behavior among Generational Cohorts

    Science.gov (United States)

    Warrington, Cartmell

    2017-01-01

    In this study, the Big Five factor model of personality traits theory was tested for its ability to predict or explain Employee Information Security Behavior (EISB), when Generational Cohort (GCOHORT) moderated the relationship between the five factors of personality and EISB. The independent variables (IVs) Extraversion, Agreeableness,…

  4. 24 CFR 1000.40 - Do lead-based paint poisoning prevention requirements apply to affordable housing activities...

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Do lead-based paint poisoning... AMERICAN HOUSING ACTIVITIES General § 1000.40 Do lead-based paint poisoning prevention requirements apply to affordable housing activities under NAHASDA? Yes, lead-based paint requirements apply to housing...

  5. What circumstances lead to non-disclosure of cancer-related information in China? A qualitative study.

    Science.gov (United States)

    Ni, Yi Hu; Alræk, Terje

    2017-03-01

    Withholding information from cancer patients is a common practice in many Asian countries, including China, Japan, and Singapore, as well as in some Western countries, such as Spain, Greece, and Italy. Much research has investigated why doctors withhold information from cancer patients generally, both in the West and the East, but little research has been done on specifically why Chinese doctors withhold such information. Three focus group interviews were conducted with a total of 16 oncologists in China. The interviews were recorded, transcribed, and translated. Qualitative data were analyzed using systematic text condensation. The result of this study revealed numerous circumstances that can lead to non-disclosure of cancer-related information. Many of these circumstances have been described in previous studies about non-disclosure in other countries. We found two additional circumstances that have not been described in previous literature and might therefore expand our current knowledge about this phenomenon; they are contradiction between laws and fear for personal safety. Numerous circumstances can lead to non-disclosure of cancer-related information. This study found two additional circumstances that might lead to non-disclosure. The findings of this study suggest further assessment and clarification about the laws that govern doctor-patient communication and that action should be taken to ensure safe working environments for Chinese oncologists.

  6. 75 FR 14179 - Agency Information Collection Activities: Form I-9 CNMI; Revision to an Existing Information...

    Science.gov (United States)

    2010-03-24

    ... SECURITY U.S. Citizenship and Immigration Services Agency Information Collection Activities: Form I-9 CNMI; Revision to an Existing Information Collection; Comment Request ACTION: 30-Day Notice of Information Collection under Review: Form I-9 CNMI, CNMI Employment Eligibility Verification; OMB Control No. 1615- 0112...

  7. Events that lead university students to change their major to Information Systems: A retroductive South African case

    Directory of Open Access Journals (Sweden)

    Lisa Florence Seymour

    2016-07-01

    Full Text Available Shortage of computing skills is a global concern as it affects national development and business success. Yet, despite high job availability and high salaries in computing professions, insufficient numbers of students are choosing to study the various computing disciplines. This South African study looks at the Information Systems (IS major which is misunderstood by high school students. This retroductive case study identifies the events which lead students to change their major to IS. The study confirms the importance of interest in a major as well as the perceived high value of a major, which feature as dominant factors in the literature. Yet these are not the initial events that lead to students changing their major to IS. Events that initiate the process include losing passion for a previous major, experiencing difficulty in a previous major as well as enjoying the introductory IS course. The paper has practical advice for IS Departments and argues for a generic first year for students as well as a focus on enjoyment and skills aligned to IS professional practice in introductory IS courses. These findings can be generalised to other majors and, hence, the theoretical contribution adds to the literature on career choice in general.

  8. Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research

    Directory of Open Access Journals (Sweden)

    Facio Flavia M

    2012-10-01

    Full Text Available Abstract Background Massively-parallel sequencing (MPS technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results. Discussion We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality. Summary The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.

  9. Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research.

    Science.gov (United States)

    Facio, Flavia M; Sapp, Julie C; Linn, Amy; Biesecker, Leslie G

    2012-10-10

    Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results. We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality. The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.

  10. Stress Leads to Aberrant Hippocampal Involvement When Processing Schema-Related Information

    Science.gov (United States)

    Vogel, Susanne; Kluen, Lisa Marieke; Fernández, Guillén; Schwabe, Lars

    2018-01-01

    Prior knowledge, represented as a mental schema, has critical impact on how we organize, interpret, and process incoming information. Recent findings indicate that the use of an existing schema is coordinated by the medial prefrontal cortex (mPFC), communicating with parietal areas. The hippocampus, however, is crucial for encoding…

  11. Sorption of lead from aqueous solution by modified activated carbon ...

    African Journals Online (AJOL)

    The present study aims to develop a simple and rapid procedure for lead (II) removal. Laboratory-scale adsorption experiments were conducted aiming to remove lead from water samples. They were based on using powdered activated carbon (PACI), which was prepared from olive stones generated, as plant wastes, and ...

  12. Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death

    Science.gov (United States)

    Graham, Nicholas A; Tahmasian, Martik; Kohli, Bitika; Komisopoulou, Evangelia; Zhu, Maggie; Vivanco, Igor; Teitell, Michael A; Wu, Hong; Ribas, Antoni; Lo, Roger S; Mellinghoff, Ingo K; Mischel, Paul S; Graeber, Thomas G

    2012-01-01

    The altered metabolism of cancer can render cells dependent on the availability of metabolic substrates for viability. Investigating the signaling mechanisms underlying cell death in cells dependent upon glucose for survival, we demonstrate that glucose withdrawal rapidly induces supra-physiological levels of phospho-tyrosine signaling, even in cells expressing constitutively active tyrosine kinases. Using unbiased mass spectrometry-based phospho-proteomics, we show that glucose withdrawal initiates a unique signature of phospho-tyrosine activation that is associated with focal adhesions. Building upon this observation, we demonstrate that glucose withdrawal activates a positive feedback loop involving generation of reactive oxygen species (ROS) by NADPH oxidase and mitochondria, inhibition of protein tyrosine phosphatases by oxidation, and increased tyrosine kinase signaling. In cells dependent on glucose for survival, glucose withdrawal-induced ROS generation and tyrosine kinase signaling synergize to amplify ROS levels, ultimately resulting in ROS-mediated cell death. Taken together, these findings illustrate the systems-level cross-talk between metabolism and signaling in the maintenance of cancer cell homeostasis. PMID:22735335

  13. 77 FR 16222 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generator...

    Science.gov (United States)

    2012-03-20

    ... Standards Applicable to Laboratories Owned by Eligible Academic Entities AGENCY: Environmental Protection... seq.), this document announces that EPA is planning to submit a request to the Office of Management... standards for laboratories owned by eligible academic entities. This ICR is scheduled to expire on July 31...

  14. Basic Information about Lead in Drinking Water

    Science.gov (United States)

    ... Health) Lead can also be transmitted through breast milk. Read more on lead exposure in pregnancy and lactating women (PDF) (302 pp, 4.3 MB, About PDF ) . Adults Lead is also harmful to adults. Adults exposed ...

  15. EPA Reaches Settlement with Two N.H. Companies for Failure to Disclose Lead Paint Information or Follow Lead-Safe Work Practices at Residential Property in Manchester

    Science.gov (United States)

    The U.S. EPA finalized a settlement agreement with two N.H. companies for their alleged failure to follow lead-safe work practices and provide proper lead paint disclosure to tenants at a residential property in Manchester, N.H.

  16. Brand Coopetition with Geographical Indications: Which Information Does Lead to Brand Differentiation?

    NARCIS (Netherlands)

    Dentoni, D.; Tonsor, G.; Calantone, R.; Peterson, C.

    2013-01-01

    Farmers and managers marketing food products with Geographical Indications (GIs) have to play a brand coopetition game: they cooperate with each other to develop a collective GI equity, yet they compete to build their individual brand and to establish market channels. Based on an online experiment

  17. 78 FR 38060 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-06-25

    ... Title XXVI of the Public Health Service (PHS) Act, as amended, supports a network of regional and... individuals with HIV infection, and to help prevent high-risk behaviors that lead to HIV transmission. As part... expansion. Trainees are asked to complete the Participant Information Form (PIF) for each activity they...

  18. Identification of suitable income generating activities to reduce ...

    African Journals Online (AJOL)

    Primary data were collected through Focus Group Discussions (FGDs), structured questionnaire, key informant interviews, direct/participant observations and secondary data through literature review. Quantitative data ... It was concluded that IGAs can make a big change in economic status of households around RNFR.

  19. Cybersecurity Activities Support to DoD Information Network Operations

    Science.gov (United States)

    2016-03-07

    Component training or certification requirements. DoDI 8530.01, March 7, 2016 ENCLOSURE 4 33 ENCLOSURE 4 CYBERSECURITY INTEGRATION INTO DoDIN...Department of Defense INSTRUCTION NUMBER 8530.01 March 7, 2016 DoD CIO SUBJECT: Cybersecurity Activities Support to DoD Information...organizational entities within the DoD (referred to collectively in this instruction as the “DoD Components”). DoDI 8530.01, March 7, 2016 2 b

  20. How to change GEBCO outreach activities with Information technologies?

    Science.gov (United States)

    Chang, E.; Park, K.

    2014-12-01

    Since 1995, when National Geographic Information Project began, we have great advance in mapping itself and information service on the earth surface in Korea whether paper maps or online service map. By reviewing geological and mine-related information service in current and comparisons of demands, GEBCO outreach master plan has been prepared. Information service cannot be separated from data production and on dissemination policies. We suggest the potential impact of the changes in information technologies such as mobile service and data fusion, and big data on GEBCO maps based. Less cost and high performance in data service will stimulate more information service; therefore it is necessary to have more customer-oriented manipulation on the data. By inquiring questionnaire, we can draw the potential needs on GEBCO products in various aspects: such as education, accessibility. The gap between experts and non-experts will decrease by digital service from the private and public organizations such as international academic societies since research funds and policies tend to pursue "openness" and "interoperability" among the domains. Some background why and how to prepare outreach activities in GEBCO will be shown.

  1. Informal Peer-Assisted Learning Groups Did Not Lead to Better Performance of Saudi Dental Students.

    Science.gov (United States)

    AbdelSalam, Maha; El Tantawi, Maha; Al-Ansari, Asim; AlAgl, Adel; Al-Harbi, Fahad

    2017-01-01

    To describe peer-assisted learning (PAL) groups formed by dental undergraduate students in a biomedical course and to investigate the association of individual and group characteristics with academic performance. In 2015, 92 fourth-year students (43 males and 49 females) in the College of Dentistry, University of Dammam, Saudi Arabia, were invited to form PAL groups to study a unit of a biomedical course. An examination was used to assess their knowledge after 2 weeks. In addition, a questionnaire and social network analysis were used to investigate (1) individual student attributes: gender, role, subject matter knowledge, grade in previous year, teaming with friends, previous communication with teammates, and content discussion, and (2) group attributes: group teacher's previous grade, number of colleagues with whom a student connected, teaming with friends, similarity of teammates' previous grades, and teacher having higher previous grades than other teammates. Regression analysis was used to assess the association of examination scores with individual and group attributes. The response rate was 80.4% (74 students: 36 males and 38 females). Students who previously scored grades A and B had higher examination scores than students with grades C/less (regression coefficient = 18.50 and 13.39) within the groups. Higher scores were not associated with working in groups including friends only (regression coefficient = 1.17) or when all students had similar previous grades (regression coefficient = 0.85). Students with previous high grades benefited to a greater extent from working in PAL groups. Similarity of teammates in PAL groups was not associated with better scores. © 2017 S. Karger AG, Basel.

  2. Activated Met signalling in the developing mouse heart leads to cardiac disease.

    Directory of Open Access Journals (Sweden)

    Christian Leo

    Full Text Available BACKGROUND: The Hepatocyte Growth Factor (HGF is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF or the constitutively activated Tpr-Met kinase to explore: i the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43 in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease.

  3. Local active information storage as a tool to understand distributed neural information processing

    Science.gov (United States)

    Wibral, Michael; Lizier, Joseph T.; Vögler, Sebastian; Priesemann, Viola; Galuske, Ralf

    2013-01-01

    Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for today's digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, definitions were given for the dynamics of these information processing operations on a local scale in space and time in a distributed system, and the specific concept of local active information storage was successfully applied to the analysis and optimization of artificial neural systems. However, no attempt to measure the space-time dynamics of local active information storage in neural data has been made to date. Here we measure local active information storage on a local scale in time and space in voltage sensitive dye imaging data from area 18 of the cat. We show that storage reflects neural properties such as stimulus preferences and surprise upon unexpected stimulus change, and in area 18 reflects the abstract concept of an ongoing stimulus despite the locally random nature of this stimulus. We suggest that LAIS will be a useful quantity to test theories of cortical function, such as predictive coding. PMID:24501593

  4. Systemic Immune Activation Leads to Neuroinflammation and Sickness Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Steven Biesmans

    2013-01-01

    Full Text Available Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.

  5. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  6. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters

    Directory of Open Access Journals (Sweden)

    Tina eNetzker

    2015-04-01

    Full Text Available Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs, which are also called natural products. Recently, it was shown that interspecies ‘talk’ between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

  7. Spatio-temporal regulation of Hsp90-ligand complex leads to immune activation.

    Directory of Open Access Journals (Sweden)

    Yasuaki eTamura

    2016-05-01

    Full Text Available Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We found that an Hsp90-cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived dendritic cells and induced peptide-specific cytotoxic T lymphocytes. Furthermore, we observed that the internalized Hsp90-peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through a endosome-recycling pathway. We also found that extracellular Hsp90 complexed with CpG-A or self-DNA stimulates production of a large amount of IFN-α from pDCs via static early endosome targeting. Thus, extracellular Hsp90 can target the antigen or nucleic acid to a static early endosome by spatio-temporal regulation. Moreover, we showed that Hsp90 associates with and delivers TLR7/9 from the ER to early endosomes for ligand recognition. Hsp90 inhibitor, geldanamycin derivative inhibited the Hsp90 association with TLR7/9, resulting in inhibition IFN-α production, leading to improvement of SLE symptoms. Interstingly, we observed that serum Hsp90 is clearly increased in patients with active SLE compared with that in patients with inactive disease. Serum Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading to stimulation of pDCs to produce IFN-α. Thus, Hsp90 plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will therefore provide a new therapeutic approach to SLE and other nucleic acid-related autoimmune diseases. We will discuss how spatio-temporal regulation of Hsp90-ligand complexes within antigen-presenting cells affects the innate immunity and adaptive immunity.

  8. A practical object-oriented approach to a development of a next generation hospital information system.

    Science.gov (United States)

    Sakamoto, N

    1998-01-01

    KIND (stands for Kyushu university hospital Information Network Database) is a five years project, which aims to provide integrated services for patients, physicians, researchers and other hospital staffs. The final product of KIND is a next generation hospital information system. A physicians' clinical workstation, for example, integrated into a secured medical information network, can electronically develop a longitudinal medical record and interface with pharmacies, laboratories, medical specialists, and radiologists, as well as develop patient census and demographic profiles, in addition to doing electronic claims. Since clinical requirements on those medical records may vary for each case, we would like to have an essential data model under the hood. We decided to introduce domain analysis method to produce a relevant domain model. A domain analysis method captures the nature of business and helps us have an essential and extensible data model. Although there are several ways to describe a domain model, we chose an object-oriented description and consequently implementation using an object-oriented database system. Once we could have a decent domain model and implemented it as an object-oriented data model, application programs can utilize those data very easy without worrying extra efforts like finding complex queries including multiple joins. More over, if an application uses decent object-oriented technologies, it allows a user to access whole aspects of data transparently. This paper describes the architecture of KIND (the system) and outlines our domain model. In this paper, we also describe a practical application of several object-oriented technologies to develop a next generation hospital information system.

  9. Three N.H. Companies Face EPA Penalties for Failing to Disclose Lead Paint Information or Follow Lead-Safe Work Practices at a Residential Property in Manchester

    Science.gov (United States)

    Three N.H. companies face significant penalties from EPA under two civil complaints filed by EPA alleging that the companies failed to follow federal lead paint regulations at a commercial and residential property in Manchester.

  10. Local active information storage as a tool to understand distributed neural information processing

    Directory of Open Access Journals (Sweden)

    Michael eWibral

    2014-01-01

    Full Text Available Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for today’s digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, such definitions were given and the specific concept of local active information storage was successfully applied to the analysis and optimization of artificial neural systems. However, no attempt to measure local active information storage in neural data has been made to date. Here we measure local active information storage on a local scale in time and space in voltage sensitive dye imaging data from area 18 of the cat. We show that storage reflects neural properties such as stimulus preferences and surprise upon unexpected stimulus change, and in area 18 reflects the abstract concept of an ongoing stimulus despite the locally random nature of this stimulus. We suggest that LAIS will be a useful quantity to test theories of cortical function, such as predictive coding.

  11. 78 FR 8550 - Notice of Submission of Proposed Information Collection to OMB HUD Lead Hazard Control Grantees...

    Science.gov (United States)

    2013-02-06

    ... notification of lead based paint hazard in federally-owned residential properties and housing receiving Federal... through the use of appropriate automated collection techniques or other forms of information technology, e... of the need for the information and proposed use: Requirements for notification of leadbased paint...

  12. Using Route and Survey Information to Generate Cognitive Maps : Differences Between Normally Sighted and Visually Impaired Individuals

    NARCIS (Netherlands)

    Steyvers, Frank J. J. M.; Kooijman, Aart C.

    Visually impaired people (VIP) have to rely on different information to generate a cognitive map of their environment than normally sighted people. This study explored the extent to which a cognitive map could be generated by auditory information of route-type and survey-type descriptions of a

  13. Activation of asparaginyl endopeptidase leads to Tau hyperphosphorylation in Alzheimer disease.

    Science.gov (United States)

    Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Tung, Yunn Chyn; Liu, Fei; Iqbal, Khalid

    2013-06-14

    Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2(PP2A). In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.

  14. Collector attachment to lead-activated sphalerite – Experiments and DFT study on pH and solvent effects

    Energy Technology Data Exchange (ETDEWEB)

    Sarvaramini, A. [Department of Chemical Engineering, Université Laval, 1065 Avenue de la médecine, Québec, Québec G1V 0A6 (Canada); Larachi, F., E-mail: faical.larachi@gch.ulaval.ca [Department of Chemical Engineering, Université Laval, 1065 Avenue de la médecine, Québec, Québec G1V 0A6 (Canada); Hart, B. [Department of Earth Sciences, Surface Science Western, The University of Western Ontario, 999 Collip Circle, P.O. Box 12, London, Ontario N6G 0J3 (Canada)

    2016-03-30

    Graphical abstract: - Highlights: • DFT and experimental study of collector interactions with Pb-activated sphalerite. • Sphalerite activation in acidic media due to surface adsorption of Pb cations. • Substitution of surface zinc atoms by Pb not supported from experiments and DFT. • Collector adsorption on activated sphalerite hindered in solvated aqueous media. • Collector adsorption on surface deposited Pb(OH){sub 2} energetically favorable. - Abstract: The interactions of diisobutyl dithiophosphinate with bare (un-activated) and lead-activated sphalerite were studied both experimentally and through DFT simulations. Sphalerite activated by lead in acidic and alkaline conditions showed considerably greater affinity for diisobutyl dithiophosphinate adsorption than bare sphalerite. Experimental observations supported by DFT simulations concur in that attachment of the solvated collector to the activated sphalerite surface is through adsorbed lead cations or lead hydroxides where as for the bare sphalerite, the collector was most stable in its solvated state and not as an adsorbed specie. Accounting for solvation effects by including a swarm of water molecules in DFT simulations was necessary to infer plausible surface interactions between collector, solvent, and bare or lead-activated sphalerite. The experimental data and DFT simulations indicate, affinity of the collector toward surface-adsorbed lead species was predicted to form stable covalent bonds between collector sulfur atoms and lead.

  15. Lead Generation and Optimization Based on Protein-Ligand Complementarity

    Directory of Open Access Journals (Sweden)

    Koji Ogata

    2010-06-01

    Full Text Available This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the protein binding site it designs structurally similar compounds considering all possible combinations of atomic species (N, C, O, CH3, NH,etc. Compounds are ranked based on a score which incorporates energetic contributions evaluated using molecular mechanics force fields. This procedure was used to design new inhibitor molecules for three serine/threonine protein kinases (p38 MAP kinase, p42 MAP kinase (ERK2, and c-Jun N-terminal kinase 3 (JNK3. For each enzyme, the calculations produce a set of potential inhibitors whose scores are in agreement with IC50 data and Ki values. Furthermore, the native ligands for each protein target, scored within the five top-ranking compounds predicted by our method, one of the top-ranking compounds predicted to inhibit JNK3 was synthesized and his inhibitory activity confirmed against ATP hydrolysis. Our computational procedure is therefore deemed to be a useful tool for generating chemically diverse molecules active against known target proteins.

  16. Lead Toxicity to the Performance, Viability, And Community Composition of Activated Sludge Microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, L; Zhi, W; Liu, YS; Karyala, S; Vikesland, PJ; Chen, X; Zhang, HS

    2015-01-20

    Lead (Pb) is a prominent toxic metal in natural and engineered systems. Current knowledge on Pb toxicity to the activated sludge has been limited to short-term (<= 24 h) toxicity. The effect of extended Pb exposure on process performance, bacterial viability, and community compositions remains unknown. We quantified the 24-h and 7-day Pb toxicity to chemical oxygen demand (COD) and NH3-N removal, bacterial viability, and community compositions using lab-scale experiments. Our results showed that 7-day toxicity was significantly higher than the short-term 24-h toxicity. Ammonia-oxidizing bacteria were more susceptible than the heterotrophs to Pb toxicity. The specific oxygen uptake rate responded quickly to Pb addition and could serve as a rapid indicator for detecting Pb pollutions. Microbial viability decreased linearly with the amount of added Pb at extended exposure. The bacterial community diversity was markedly reduced with elevated Pb concentrations. Surface analysis suggested that the adsorbed form of Pb could have contributed to its toxicity along with the dissolved form. Our study provides for the first time a systematic investigation of the effect of extended exposure of Pb on the performance and microbiology of aerobic treatment processes, and it indicates that long-term Pb toxicity has been underappreciated by previous studies.

  17. Shiga Toxins: Intracellular Trafficking to the ER Leading to Activation of Host Cell Stress Responses

    Directory of Open Access Journals (Sweden)

    Moo-Seung Lee

    2010-06-01

    Full Text Available Despite efforts to improve hygenic conditions and regulate food and drinking water safety, the enteric pathogens, Shiga toxin-producing Escherichia coli (STEC and Shigella dysenteriae serotype 1 remain major public health concerns due to widespread outbreaks and the severity of extra-intestinal diseases they cause, including acute renal failure and central nervous system complications. Shiga toxins are the key virulence factors expressed by these pathogens mediating extra-intestinal disease. Delivery of the toxins to the endoplasmic reticulum (ER results in host cell protein synthesis inhibition, activation of the ribotoxic stress response, the ER stress response, and in some cases, the induction of apoptosis. Intrinsic and/or extrinsic apoptosis inducing pathways are involved in executing cell death following intoxication. In this review we provide an overview of the current understanding Shiga toxin intracellular trafficking, host cellular responses to the toxin and ER stress-induced apoptosis with an emphasis on recent findings.

  18. GPCR Homology Model Generation for Lead Optimization.

    Science.gov (United States)

    Tautermann, Christofer S

    2018-01-01

    The vast increase of recently solved GPCR X-ray structures forms the basis for GPCR homology modeling to atomistic accuracy. Nowadays, homology models can be employed for GPCR-ligand optimization and have been reported as invaluable tools for drug design in the last few years. Elucidation of the complex GPCR pharmacology and the associated GPCR conformations made clear that different homology models have to be constructed for different activation states of the GPCRs. Therefore, templates have to be chosen accordingly to their sequence homology as well as to their activation state. The subsequent ligand placement is nontrivial, as some recent X-ray structures show very unusual ligand binding sites and solvent involvement, expanding the space of the putative ligand binding site from the generic retinal binding pocket to the whole receptor. In the present study, a workflow is presented starting from the selection of the target sequence, guiding through the GPCR modeling process, and finishing with ligand placement and pose validation.

  19. Differential Reovirus-Specific and Herpesvirus-Specific Activator Protein 1 Activation of Secretogranin II Leads to Altered Virus Secretion.

    Science.gov (United States)

    Berard, Alicia R; Severini, Alberto; Coombs, Kevin M

    2015-12-01

    Viruses utilize host cell machinery for propagation and manage to evade cellular host defense mechanisms in the process. Much remains unknown regarding how the host responds to viral infection. We recently performed global proteomic screens of mammalian reovirus TIL- and T3D-infected and herpesvirus (herpes simplex virus 1 [HSV-1])-infected HEK293 cells. The nonenveloped RNA reoviruses caused an upregulation, whereas the enveloped DNA HSV-1 caused a downregulation, of cellular secretogranin II (SCG2). SCG2, a member of the granin family that functions in hormonal peptide sorting into secretory vesicles, has not been linked to virus infections previously. We confirmed SCG2 upregulation and found SCG2 phosphorylation by 18 h postinfection (hpi) in reovirus-infected cells. We also found a decrease in the amount of reovirus secretion from SCG2 knockdown cells. Similar analyses of cells infected with HSV-1 showed an increase in the amount of secreted virus. Analysis of the stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) pathway indicated that each virus activates different pathways leading to activator protein 1 (AP-1) activation, which is the known SCG2 transcription activator. We conclude from these experiments that the negative correlation between SCG2 quantity and virus secretion for both viruses indicates a virus-specific role for SCG2 during infection. Mammalian reoviruses affect the gastrointestinal system or cause respiratory infections in humans. Recent work has shown that all mammalian reovirus strains (most specifically T3D) may be useful oncolytic agents. The ubiquitous herpes simplex viruses cause common sores in mucosal areas of their host and have coevolved with hosts over many years. Both of these virus species are prototypical representatives of their viral families, and investigation of these viruses can lead to further knowledge of how they and the other more pathogenic members of their respective families interact with the

  20. Genetics of autism spectrum disorder: an update on copy number variations leading to autism in the next generation sequencing era.

    Science.gov (United States)

    AlSagob, Maysoon; Colak, Dilek; Kaya, Namik

    2015-05-01

    Autism spectrum disorder (ASD) is a large group of neurodevelopmental conditions that share common characteristics such as social and language impairment and repetitive and stereotypic behaviors. It is reported that ASD is on increase in recent years reaching ratios up to 1 in 68 children. The disease is seen four times more frequently in males than females. ASD is heritable with complex inheritance and genetic heterogeneity, and frequently coexists with other diseases such as intellectual disability, seizure disorders, and fragile-x. Recent advances in genomic technologies have led to a greater understanding of genetic mechanisms in ASD, discovery of novel genetic loci and risk factors, as well as submicroscopic chromosomal changes also known as copy number variations (CNVs). Here we review recent developments in the genetics field and hereditary and sporadic CNVs leading to ASD.

  1. Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates, from Which Bacteria Subsequently Escape

    Science.gov (United States)

    Svensson, Lisbeth; Baumgarten, Maria; Mörgelin, Matthias

    2014-01-01

    Platelet activation and aggregation have been reported to occur in response to a number of Gram-positive pathogens. Here, we show that platelet aggregates induced by Streptococcus pyogenes were unstable and that viable bacteria escaped from the aggregates over time. This was not due to differential activation in response to the bacteria compared with physiological activators. All the bacterial isolates induced significant platelet activation, including integrin activation and alpha and dense-granule release, at levels equivalent to those induced by potent physiological platelet activators that induced stable aggregates. The ability to escape the aggregates and to resist the antibacterial effects of platelets was dependent on active protein synthesis by the bacteria within the aggregate. We conclude that S. pyogenes bacteria can temporarily cover themselves with activated platelets, and we propose that this may facilitate survival of the bacteria in the presence of platelets. PMID:25069984

  2. {delta}-ALAD activity variations in red blood cells in response to lead accumulation in rock doves (Columba livia)

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.; Tejedor, M.C. [Universidad de Alcala de Henares (Spain)

    1992-10-01

    The enzyme {delta}-aminolevulinic acid dehydratase ({delta}-ALAD, E.C. 4.2.1.24), catalyses the second step of the haeme biosynthetic pathway and is required to maintain the haemoglobin and cytochrome content in red cells. {delta}-ALAD is not only found in bone marrow cells, the major site of haeme synthesis, but also in circulating erythrocytes and other tissues. An inverse correlation was found between {delta}-ALAD activity in red blood cells and lead concentration in the blood. The degree of {delta}-ALAD inhibition in erythrocytes has been widely accepted as a standard bioassay to detect acute and chronic lead exposure in humans and in avians. The value of this parameter as an indicator for environmental lead has been often reported in doves and Scanlon. In lead-treated rats, an increase in {delta}-ALAD activity in bone marrow cells and in blood samples was shown by radioimmunoassay at 5 and 9 days after the treatment. Similarly, the amount of {delta}-ALAD seems to be more sensitive to lead in avian species than in mammals, the usefulness of blood {delta}-ALAD activity as an index of lead exposure has already been questioned by Hutton in the pigeon and by Jaffe et al. in humans. The present investigation studied the toxic effects of lead on rock dove red blood cell {delta}-ALAD activity in two situations: in doves treated with lead acetate in the laboratory and in doves exposed to the environment of Alcala de Henares. The final lead blood concentrations were lower in the environmental than in the laboratory doves. {delta}-ALAD activity in bone marrow cells and the relationships between lead accumulation and enzyme activity in red cells, are examined. 20 refs., 5 figs., 1 tab.

  3. Feed-forward loops and diamond motifs lead to tunable transmission of information in the frequency domain.

    Science.gov (United States)

    de Ronde, W H; Tostevin, F; Ten Wolde, P R

    2012-08-01

    Using a Gaussian model, we study the transmission of time-varying biochemical signals through feed-forward motifs and diamond motifs. To this end, we compute the frequency dependence of the gain, the noise, as well as their ratio, the gain-to-noise ratio, which measures how reliably a network transmits signals at different frequencies. We find that both coherent and incoherent feed-forward motifs can either act as low-pass or high-pass filters for information: The frequency dependence of the gain-to-noise ratio increases or decreases with increasing frequency, respectively. Our analysis of diamond motifs reveals that cooperative activation of the output component can increase the gain-to-noise ratio. This means that from the perspective of information transmission, it can be beneficial to split the input signal in two and recombine the two propagated signals at the output. Cooperative activation can be implemented via the formation of homo- or heteromultimers that then bind and activate the output component or via the binding of individual molecules of the intermediate species to the output component.

  4. Activation analysis of targets and lead in a lead slowing down spectrometer system

    Directory of Open Access Journals (Sweden)

    Yongdeok Lee

    2018-02-01

    Full Text Available A neutron generation system was developed to induce fissile fission in a lead slowing down spectrometer (LSDS system. The source neutron is one of the key factors for LSDS system work. The LSDS was developed to quantify the isotopic contents of fissile materials in spent nuclear fuel and recycled fuel. The source neutron is produced at a multilayered target by the (e,γ(γ,n reaction and slowed down at the lead medium. Activation analysis of the target materials is necessary to estimate the lifetime, durability, and safety of the target system. The CINDER90 code was used for the activation analysis, and it can involve three-dimensional geometry, position dependent neutron flux, and multigroup cross-section libraries. Several sensitivity calculations for a metal target with different geometries, materials, and coolants were done to achieve a high neutron generation rate and a low activation characteristic. Based on the results of the activation analysis, tantalum was chosen as a target material due to its better activation characteristics, and helium gas was suggested as a coolant. In addition, activation in a lead medium was performed. After a distance of 55 cm from the lead surface to the neutron incidence, the neutron intensity dramatically decreased; this result indicates very low activation.

  5. 77 FR 66502 - Agency Information Collection Activity; Notice of Request for Approval to Collect New Information...

    Science.gov (United States)

    2012-11-05

    ... Research and Innovative Technology Administration Agency Information Collection Activity; Notice of Request... AGENCY: Bureau of Transportation Statistics (BTS), Research and Innovative Technology Administration... Bureau of Transportation Statistics (BTS), U.S. Department of Transportation. This information collection...

  6. Efficient methylammonium lead iodide perovskite solar cells with active layers from 300 to 900 nm

    Energy Technology Data Exchange (ETDEWEB)

    Momblona, C.; Malinkiewicz, O.; Soriano, A.; Gil-Escrig, L.; Bandiello, E.; Scheepers, M.; Bolink, H. J., E-mail: henk.bolink@uv.es [Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático J. Beltrán 2, 46980 Paterna, Valencia (Spain); Roldán-Carmona, C. [Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático J. Beltrán 2, 46980 Paterna, Valencia (Spain); Department of Physical Chemistry and Applied Thermodynamics, University of Córdoba, Campus Rabanales, Ed. C3, 14014, Córdoba (Spain); Edri, E. [Department of Materials and Interfaces, Weizmann Institute of Science, Herzl St. 34, Rehovot 76100 (Israel)

    2014-08-01

    Efficient methylammonium lead iodide perovskite-based solar cells have been prepared in which the perovskite layer is sandwiched in between two organic charge transporting layers that block holes and electrons, respectively. This configuration leads to stable and reproducible devices that do not suffer from strong hysteresis effects and when optimized lead to efficiencies close to 15%. The perovskite layer is formed by using a dual-source thermal evaporation method, whereas the organic layers are processed from solution. The dual-source thermal evaporation method leads to smooth films and allows for high precision thickness variations. Devices were prepared with perovskite layer thicknesses ranging from 160 to 900 nm. The short-circuit current observed for these devices increased with increasing perovskite layer thickness. The main parameter that decreases with increasing perovskite layer thickness is the fill factor and as a result optimum device performance is obtained for perovskite layer thickness around 300 nm. However, here we demonstrate that with a slightly oxidized electron blocking layer the fill factor for the solar cells with a perovskite layer thickness of 900 nm increases to the same values as for the devices with thin perovskite layers. As a result the power conversion efficiencies for the cells with 300 and 900 nm are very similar, 12.7% and 12%, respectively.

  7. A single tri-axial accelerometer-based real-time personal life log system capable of activity classification and exercise information generation.

    Science.gov (United States)

    Lee, Myong-Woo; Khan, Adil Mehmood; Kim, Ji-Hwan; Cho, Young-Sun; Kim, Tae-Seong

    2010-01-01

    Recording a personal life log (PLL) of daily activities is an emerging technology for u-lifecare and e-health services. In this paper, we present an accelerometer-based personal life log system capable of human activity classification and exercise information generation. In our system, we use a tri-axial accelerometer and a real-time activity recognition scheme in which a set of augmented features of accelerometer signals, processed with Linear Discriminant Analysis (LDA), is classified by our hierarchical artificial neural network classifier: in the lower level of the classifier, a state of an activity is recognized based on the statistical and spectral features; in the upper level, an activity is recognized with a set of augmented features including autoregressive (AR) coefficients, signal magnitude area (SMA), and tilt angles (TA). Upon the recognition of each activity, we further estimate exercise information such as energy expenditure based on Metabolic Equivalents (METS), step count, walking distance, walking speed, activity duration, etc. Our PLL system functions in real-time and all information generated from our system is archived in a daily-log database. By testing our system on seven different daily activities, we have obtained an average accuracy of 84.8% in activity recognition and generated their relative exercise information.

  8. The Influence of Lead on Generation of Signalling Molecules and Accumulation of Flavonoids in Pea Seedlings in Response to Pea Aphid Infestation

    Directory of Open Access Journals (Sweden)

    Agnieszka Woźniak

    2017-08-01

    Full Text Available The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects, on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski seedlings and then during infestation by the pea aphid (Acyrthosiphon pisum Harris. The second objective was to verify whether the presence of lead in pea seedling organs and induction of signalling pathways dependent on the concentration of this metal trigger defense responses to A. pisum. Therefore, the profile of flavonoids and expression levels of genes encoding enzymes of the flavonoid biosynthesis pathway (phenylalanine ammonialyase and chalcone synthase were determined. A significant accumulation of total salicylic acid (TSA and abscisic acid (ABA was recorded in the roots and leaves of pea seedlings growing on lead-supplemented medium and next during infestation by aphids. Increased generation of these phytohormones strongly enhanced the biosynthesis of flavonoids, including a phytoalexin, pisatin. This research provides insights into the cross-talk between the abiotic (lead and biotic factor (aphid infestation on the level of the generation of signalling molecules and their role in the induction of flavonoid biosynthesis.

  9. Instructional leadership in elementary science: How are school leaders positioned to lead in a next generation science standards era?

    Science.gov (United States)

    Winn, Kathleen Mary

    The Next Generation Science Standards (NGSS) are the newest K-12 science content standards created by a coalition of educators, scientists, and researchers available for adoption by states and schools. Principals are important actors during policy implementation especially since principals are charged with assuming the role of an instructional leader for their teachers in all subject areas. Science poses a unique challenge to the elementary curricular landscape because traditionally, elementary teachers report low levels of self-efficacy in the subject. Support in this area therefore becomes important for a successful integration of a new science education agenda. This study analyzed self-reported survey data from public elementary principals (N=667) to address the following three research questions: (1) What type of science backgrounds do elementary principals have? (2) What indicators predict if elementary principals will engage in instructional leadership behaviors in science? (3) Does self-efficacy mediate the relationship between science background and a capacity for instructional leadership in science? The survey data were analyzed quantitatively. Descriptive statistics address the first research question and inferential statistics (hierarchal regression analysis and a mediation analysis) answer the second and third research questions.The sample data show that about 21% of elementary principals have a formal science degree and 26% have a degree in a STEM field. Most principals have not had recent experience teaching science, nor were they every exclusively a science teacher. The analyses suggests that demographic, experiential, and self-efficacy variables predict instructional leadership practices in science.

  10. to generation

    Directory of Open Access Journals (Sweden)

    Michał Otręba

    2014-09-01

    Full Text Available Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. This article presents selected hypopigmentary disorders, which can be divided into hypomelanocytoses and hypomelanoses. Hereditary hypomelanoses are caused by abnormal melanin biosynthesis as well as by abnormal transfer of mature melanosomes to melanocyte dendrites and to neighboring cells. These disorders are represented by oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, Menkes syndrome and phenylketonuria, and are caused by different mutations of the following genes: TYR, P, TRP1, MATP, HPS, CHS, MYO5A, RAB27A, MLPH, ATP7A and PAH. Oculocutaneous albinism is caused by a deficiency of melanin pigment in the skin, hair, and eye and results from mutations in the TYR, P, TRP1 and MATP genes involved in the biosynthesis of melanin pigment. Mutations in the HPS, CHS, MYO5A, RAB27A and MLPH genes, which regulate the biogenesis, maturation and transfer of me-lanosomes to neighboring cells, are responsible for such disorders as Hermansky-Pudlak, Chediak-Higashi and Griscelli syndromes. In turn, mutations of the ATP7A and PAH genes, regulating intracellular copper concentration and activity of phenylalanine hydroxylase, lead to Menkes syndrome and phenylketonuria.

  11. Spanish Young Generation (JJNN) Activities

    Energy Technology Data Exchange (ETDEWEB)

    Millan, Miguel [INITEC Nuclear- Westinghouse, Padilla 17, 28006 Madrid (Spain)

    2008-07-01

    Spanish Young Generation has been very active during 2006-2008. JJNN have mainly focused on communication activities, as conferences at universities, schools and nuclear companies. Lately, becoming in referent of the young politics, journalist and the young people in Nuclear Subjects is the new and most challenging target of the Spanish Young Generation. In order to accomplish with their objects and commitments with their members, JJNN are developing all kinds of activities focused in the young people and the JJNN members. (authors)

  12. Passive Reactive Berm (PRBerm) to Provide Low Maintenance Lead Containment at Active Small Arms Firing Ranges

    Science.gov (United States)

    2012-01-01

    A nonwoven geomembrane fabric is a barrier between native soils and the ballistic impact media. Amended sand is placed on top of the newly...store bullets. Earthen backstops require immediate care to revegetate, to prevent potential ongoing erosion problems. Use of fiber mulch, filter fabric...different ballistic sand and amendments*. Lysimeter study and amendments Lead b (µg/L) DOC (mg/L) pH Filtered Total Study Goals 150 50 6 to 9

  13. From generative fit to generative capacity: exploring an emerging dimension of information systems design and task performance

    NARCIS (Netherlands)

    Avital, M.; Te'eni, D.

    2009-01-01

    Information systems (IS) research has been long concerned with improving task-related performance. The concept of fit is often used to explain how system design can improve performance and overall value. So far, the literature has focused mainly on performance evaluation criteria that are based on

  14. Experimental pain leads to reorganisation of trapezius electromyography during computer work with active and passive pauses

    DEFF Research Database (Denmark)

    Samani, Afshin; Holtermann, Andreas; Søgaard, Karen

    2009-01-01

    in one day, with passive (relax) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 40 s without and with presence of experimental pain. Surface EMG signals were recorded from four parts of the trapezius. The centroid of exposure variation analysis along the time axis...... was lower during computer work with active pauses when compared with passive one in all muscle parts (P rest time decreased in ascending part. The results of this study showed a more variable...... trapezius activity pattern and increased activity with active compared with passive pauses, a lowered trapezius rest with presence of experimental pain, and increased activity in the transverse and ascending parts of trapezius due to experimental pain during computer work. Acute pain led to muscle...

  15. Mobilization of copper ions in human peripheral lymphocytes by catechins leading to oxidative DNA breakage: A structure activity study.

    Science.gov (United States)

    Farhan, Mohd; Zafar, Atif; Chibber, Sandesh; Khan, Husain Yar; Arif, Hussain; Hadi, S M

    2015-08-15

    Epidemiological studies suggest that dietary consumption of plant polyphenols is related to a lower incidence of various cancers. Among these compounds catechins (present in green tea and other beverages) are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. Thus these compounds can be used as leads to synthesize novel anticancer drugs with greater bioavailability. In view of this in this paper we have examined the chemical basis of cytotoxicity of catechins by studying the structure-activity relationship between catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG). Using single cell alkaline gel electrophoresis (comet assay) we have established the relative efficiency of cellular DNA breakage as EGCG>EGC>EC>C. We also show that cellular DNA breakage is the result of mobilization of copper ions bound to chromatin and the generation of reactive oxygen species. Further the relative DNA binding affinity order was confirmed using molecular docking and thermodynamic studies by studying the interaction of catechins with calf thymus DNA. The results suggest that the synthesis of any novel anti cancer molecule based on the structure of catechins should have as many galloyl moieties as possible resulting in an increased number of hydroxyl groups that may facilitate the binding of the molecule to cellular DNA. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. A Bio-inspired Collision Avoidance Model Based on Spatial Information Derived from Motion Detectors Leads to Common Routes.

    Science.gov (United States)

    Bertrand, Olivier J N; Lindemann, Jens P; Egelhaaf, Martin

    2015-11-01

    Avoiding collisions is one of the most basic needs of any mobile agent, both biological and technical, when searching around or aiming toward a goal. We propose a model of collision avoidance inspired by behavioral experiments on insects and by properties of optic flow on a spherical eye experienced during translation, and test the interaction of this model with goal-driven behavior. Insects, such as flies and bees, actively separate the rotational and translational optic flow components via behavior, i.e. by employing a saccadic strategy of flight and gaze control. Optic flow experienced during translation, i.e. during intersaccadic phases, contains information on the depth-structure of the environment, but this information is entangled with that on self-motion. Here, we propose a simple model to extract the depth structure from translational optic flow by using local properties of a spherical eye. On this basis, a motion direction of the agent is computed that ensures collision avoidance. Flying insects are thought to measure optic flow by correlation-type elementary motion detectors. Their responses depend, in addition to velocity, on the texture and contrast of objects and, thus, do not measure the velocity of objects veridically. Therefore, we initially used geometrically determined optic flow as input to a collision avoidance algorithm to show that depth information inferred from optic flow is sufficient to account for collision avoidance under closed-loop conditions. Then, the collision avoidance algorithm was tested with bio-inspired correlation-type elementary motion detectors in its input. Even then, the algorithm led successfully to collision avoidance and, in addition, replicated the characteristics of collision avoidance behavior of insects. Finally, the collision avoidance algorithm was combined with a goal direction and tested in cluttered environments. The simulated agent then showed goal-directed behavior reminiscent of components of the navigation

  17. Can Pluralistic Approaches Based upon Unknown Languages Enhance Learner Engagement and Lead to Active Social Inclusion?

    Science.gov (United States)

    Dahm, Rebecca

    2017-01-01

    One way to foster active social inclusion is to enable students to develop a positive attitude to "foreignness". Creating a situation where mainstream students are less wary of foreign languages and cultures, and where newcomers feel their linguistic background is being valued, provides favourable conditions for the inclusion of these…

  18. Transcriptome profiling of radish (Raphanus sativus L.) root and identification of genes involved in response to Lead (Pb) stress with next generation sequencing.

    Science.gov (United States)

    Wang, Yan; Xu, Liang; Chen, Yinglong; Shen, Hong; Gong, Yiqin; Limera, Cecilia; Liu, Liwang

    2013-01-01

    Lead (Pb), one of the most toxic heavy metals, can be absorbed and accumulated by plant roots and then enter the food chain resulting in potential health risks for human beings. The radish (Raphanus sativus L.) is an important root vegetable crop with fleshy taproots as the edible parts. Little is known about the mechanism by which radishes respond to Pb stress at the molecular level. In this study, Next Generation Sequencing (NGS)-based RNA-seq technology was employed to characterize the de novo transcriptome of radish roots and identify differentially expressed genes (DEGs) during Pb stress. A total of 68,940 assembled unique transcripts including 33,337 unigenes were obtained from radish root cDNA samples. Based on the assembled de novo transcriptome, 4,614 DEGs were detected between the two libraries of untreated (CK) and Pb-treated (Pb1000) roots. Gene Ontology (GO) and pathway enrichment analysis revealed that upregulated DEGs under Pb stress are predominately involved in defense responses in cell walls and glutathione metabolism-related processes, while downregulated DEGs were mainly involved in carbohydrate metabolism-related pathways. The expression patterns of 22 selected genes were validated by quantitative real-time PCR, and the results were highly accordant with the Solexa analysis. Furthermore, many candidate genes, which were involved in defense and detoxification mechanisms including signaling protein kinases, transcription factors, metal transporters and chelate compound biosynthesis related enzymes, were successfully identified in response to heavy metal Pb. Identification of potential DEGs involved in responses to Pb stress significantly reflected alterations in major biological processes and metabolic pathways. The molecular basis of the response to Pb stress in radishes was comprehensively characterized. Useful information and new insights were provided for investigating the molecular regulation mechanism of heavy metal Pb accumulation and

  19. Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B

    2017-01-01

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Lead from hunting activities and its potential environmental threat to wildlife in a protected wetland in Yucatan, Mexico.

    Science.gov (United States)

    Arcega-Cabrera, Flor; Noreña-Barroso, Elsa; Oceguera-Vargas, Ismael

    2014-02-01

    This study provides insights into the status of lead in the protected wetland of El Palmar, located on the northwestern littoral of the Yucatan Peninsula. This reserve is ecologically and economically important because it provides feeding and breeding habitats for many species, as well as being an ecotourism destination (especially for bird watching). Although it is a protected area, duck species are heavily hunted within the reserve during the winter. As a result, animals feeding or living in sediments could be exposed to anthropogenic lead. Total lead and its geochemical fractionated forms were measured in sediment cores from six selected sites in "El Palmar" wetland, during pre- and post-hunting seasons, to approximate the potential environmental threat (especially for benthonic living/feeding organisms). Anthropogenic lead concentrations detected in soil cores ranged from below the minimum infaunal community effect level (30.24 μg g(-1)) during the pre-hunting season, to bordering the probable infaunal community effect level (112.18 μg g(-1)) during the post-hunting season, according to SquiiRTs NOAA guidelines. Yet, these results were lower than expected based on the intensity of hunting. Consequently, this article explores the possibility that the lower than expected lead concentration in sediments results from (1) degradation of shot and transformation to soluble or particulate forms; or (2) ingestion of lead shot by benthic and other lacustrine species living in the protected area. Geochemical fractionation of lead demonstrated that in the top 6 cm of the soil column at heavily active hunting sites (EP5 and EP6), lead was associated with the lithogenic fraction (average 45 percent) and with the organic fraction (average 20 percent). Bioavailable lead (sum of lead adsorbed to the carbonates, Fe/Mn oxyhydroxides and organic fractions) in sediments was lower than 50 percent for the heavily active hunting areas and higher for the rest of the sites

  1. 78 FR 16509 - Amendment to Information Collection Activity; Comment Request

    Science.gov (United States)

    2013-03-15

    ... data and information on the subject's work and education history. 2--Follow-Up Surveys. There are three... important predictors of later performance in the labor market, education, etc. Respondents: Respondents to...

  2. Psychological determinants of information searching activity.

    Science.gov (United States)

    Gorunova, L

    2012-01-01

    The paper deals with the application of the activity theory in describing psychological determinants of the information searching activity. The notions of information behavior, information retrieval, information competence, information retrieval activity given in Russian and English scientific literature are compared. The research approach to the information retrieval activity based on the principles developed in the Russian theory of activity is described; and the fundamentals of G. Sukhodolsky's generalized conception of activity are presented for the first time. Analysis of empirical researches showed that specific features of information search depend on how the user evaluates information resources, information, conditions and results of search. Psychological determiners of information search may be detected as the system of evaluative alternatives, which is generated by the user during the process of his experience growth. We discovered that user's evaluation system is also related to his individual typological and personal regulative features and determines the choice of the search strategy.

  3. Ethanol increases p190RhoGAP activity, leading to actin cytoskeleton rearrangements.

    Science.gov (United States)

    Selva, Javier; Egea, Gustavo

    2011-12-01

    We previously reported that cells chronically exposed to ethanol show alterations in actin cytoskeleton organization and dynamics in primary cultures of newborn rat astrocytes, a well-established in vitro model for foetal alcohol spectrum disorders. These alterations were attributed to a decrease in the cellular levels of active RhoA (RhoA-GTP), which in turn was produced by an increase in the total RhoGAP activity. We here provide evidence that p190RhoGAPs are the main factors responsible for such increase. Thus, in astrocytes chronically exposed to ethanol we observe: (i) an increase in p190A- and p190B-associated RhoGAP activity; (ii) a higher binding of p190A and p190B to RhoA-GTP; (iii) a higher p120RasGAP-p190A RhoGAP complex formation; and (iv) the recruitment of both p190RhoGAPs to the plasma membrane. The simultaneous silencing of both p190 isoforms prevents the actin rearrangements and the total RhoGAP activity increase triggered both by ethanol. Therefore, our data directly points p190RhoGAPs as ethanol-exposure molecular targets on glial cells of the CNS. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  4. Design of a leading indicator for Costa Rican economic activity

    Directory of Open Access Journals (Sweden)

    Carlos Chaverri Morales

    2014-08-01

    Full Text Available This paper presents the results of estimating three leading indicators for the turning points of the economic activity in Costa Rica. This was done following the methodology proposed by the Organization for Economic Cooperation and Development (OECD. The Monthly Economic Activity Index (IMAE in Spanish was selected as the reference variable.  A total of 270 data series were analyzed including monetary, real and job market variables, as well as price indices, external sector indicators and fiscal sector variables. The real sector information was disaggregated into three levels, which included the classification of data at an industrial level using the International Standard Industrial Classification (ISIC with two digits, information from the agricultural sector based on the Central Product Classification (CPC and information from the manufacturing sector.  A leading indicator was developed for each level of aggregation, resulting in average leads of 7 to 12 months compared to the reference variable.

  5. AMPK over-activation leads to accumulation of α-synuclein oligomers and decrease of neurites

    Science.gov (United States)

    Jiang, Peizhou; Gan, Ming; Ebrahim, Abdul Shukkur; Castanedes-Casey, Monica; Dickson, Dennis W.; Yen, Shu-Hui C.

    2012-01-01

    Neuronal inclusions of α-synuclein (α-syn), termed Lewy bodies, are a hallmark of Parkinson disease (PD). Increased α-syn levels can occur in brains of aging human and neurotoxin treated mice. Since previous studies have shown increased brain lactate levels in aging brains, in PD affected subjects when compared to age-matched controls, and in mice treated with MPTP, we tested the effects of lactate exposure on α-syn in a cell based-study. We demonstrated that (i) lactate treatment led to α-syn accumulation and oligomerization in a time- and concentration-dependent manner, (ii) such alterations were mediated via adenosine-monophosphate activated protein kinase (AMPK) and associated with increasing cytoplasmic phosphorylated AMPK levels, (iii) AMPK activation facilitated α-syn accumulation and phosphorylation, (iv) lactate treatment or overexpression of active form of AMPK decreased α-syn turnover and neurite outgrowth and (v) Lewy body-bearing neurons displayed abnormal cytoplasmic distribution of phosphorylated AMPK, which normally is located in nuclei. Together, our results suggest that chronic neuronal accumulation of α-syn induced by lactate-triggered AMPK activation in aging brains may be a novel mechanism underlying α-synucleionpathies in PD and related disorders. PMID:23200460

  6. Digital imaging information technology for biospeckle activity assessment relative to bacteria and parasites.

    Science.gov (United States)

    Ramírez-Miquet, Evelio E; Cabrera, Humberto; Grassi, Hilda C; de J Andrades, Efrén; Otero, Isabel; Rodríguez, Dania; Darias, Juan G

    2017-08-01

    This paper reports on the biospeckle processing of biological activity using a visualization scheme based upon the digital imaging information technology. Activity relative to bacterial growth in agar plates and to parasites affected by a drug is monitored via the speckle patterns generated by a coherent source incident on the microorganisms. We present experimental results to demonstrate the potential application of this methodology for following the activity in time. The digital imaging information technology is an alternative visualization enabling the study of speckle dynamics, which is correlated to the activity of bacteria and parasites. In this method, the changes in Red-Green-Blue (RGB) color component density are considered as markers of the growth of bacteria and parasites motility in presence of a drug. The RGB data was used to generate a two-dimensional surface plot allowing an analysis of color distribution on the speckle images. The proposed visualization is compared to the outcomes of the generalized differences and the temporal difference. A quantification of the activity is performed using a parameterization of the temporal difference method. The adopted digital image processing technique has been found suitable to monitor motility and morphological changes in the bacterial population over time and to detect and distinguish a short term drug action on parasites.

  7. GABAergic striatal neurons project dendrites and axons into the postnatal subventricular zone leading to calcium activity

    Directory of Open Access Journals (Sweden)

    Stephanie Z Young

    2014-01-01

    Full Text Available GABA regulates the behavior of neuroblasts and neural progenitor cells in the postnatal neurogenic subventricular zone (SVZ through GABAA receptor (GABAAR-mediated calcium increases. However, the source of GABA necessary for sufficient GABAAR-mediated depolarization and calcium increase has remained speculative. Here, we explored whether GABAergic striatal neurons functionally connect with SVZ cells. Using patch clamp recordings or single cell electroporation, striatal neurons along the SVZ were filled with a fluorescent dye revealing that they send both dendrites and axons into the SVZ. About 93% of the recorded neurons were medium spiny or aspiny GABAergic neurons and each neuron sent 3-4 processes into the SVZ covering ~56 µm. Using calcium imaging, we found that depolarization of striatal neurons led to increased calcium activity in SVZ cells that were mediated by GABAAR activation. Collectively, these findings undercover a novel mode of signaling in the SVZ providing a mechanism of brain activity-mediated regulation of postnatal neurogenesis through GABAergic striatal activity.

  8. Active Referral Intervention following Fragility Fractures Leads to Enhanced Osteoporosis Follow-Up Care

    Directory of Open Access Journals (Sweden)

    Michelle T. Sugi

    2012-01-01

    Full Text Available At one major urban academic medical center, patients aged 50 years and older with fragility fractures were identified and scheduled or assisted in referral into osteoporosis medical management appointments. We evaluated the efficacy of an active intervention program at overcoming the logistical barriers and improving proper osteoporosis follow-up for persons who have sustained a fragility fracture. Of 681 patients treated for defined fractures, 168 were eligible and consented for the study of fragility fractures. Of those enrolled, 91 (54.2% had appropriate osteoporosis follow-up on initial interview, and overall 120 (71.4% had successful osteoporosis follow-up following our active intervention. Seventy patients (41.7% were deemed to have no osteoporosis follow-up, and, of these, 48 were successfully referred to a scheduling coordinator. The scheduling coordinator was able to contact 37 (77% patients to schedule proper follow-up, and, of these, 29 (78.4% confirmed receiving an appropriate follow-up appointment. Active intervention and assisted scheduling for patients with recent fragility fractures improved the self-reported rate of osteoporosis follow-up from 54.2% to 71.4%.

  9. Music training leads to the development of timbre-specific gamma band activity.

    Science.gov (United States)

    Shahin, Antoine J; Roberts, Larry E; Chau, Wilkin; Trainor, Laurel J; Miller, Lee M

    2008-05-15

    Oscillatory gamma band activity (GBA, 30-100 Hz) has been shown to correlate with perceptual and cognitive phenomena including feature binding, template matching, and learning and memory formation. We hypothesized that if GBA reflects highly learned perceptual template matching, we should observe its development in musicians specific to the timbre of their instrument of practice. EEG was recorded in adult professional violinists and amateur pianists as well as in 4- and 5-year-old children studying piano in the Suzuki method before they commenced music lessons and 1 year later. The adult musicians showed robust enhancement of induced (non-time-locked) GBA, specifically to their instrument of practice, with the strongest effect in professional violinists. Consistent with this result, the children receiving piano lessons exhibited increased power of induced GBA for piano tones with 1 year of training, while children not taking lessons showed no effect. In comparison to induced GBA, evoked (time-locked) gamma band activity (30-90 Hz, approximately 80 ms latency) was present only in adult groups. Evoked GBA was more pronounced in musicians than non-musicians, with synchronization equally exhibited for violin and piano tones but enhanced for these tones compared to pure tones. Evoked gamma activity may index the physical properties of a sound and is modulated by acoustical training, while induced GBA may reflect higher perceptual learning and is shaped by specific auditory experiences.

  10. Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion.

    Science.gov (United States)

    Luethi, Matthias S; Friese, Malte; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

    2016-10-01

    Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. Local active information storage as a tool to understand distributed neural information processing

    OpenAIRE

    Michael eWibral; Joseph eLizier; Sebastian eVögler; Viola ePriesemann; Ralf eGaluske

    2014-01-01

    Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for today's digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, definitions were given for the dynamics of these information processing operations on a local scale in space and ...

  12. Do all sedentary activities lead to weight gain: sleep does not.

    Science.gov (United States)

    Chaput, Jean-Philippe; Klingenberg, Lars; Sjödin, Anders

    2010-11-01

    To discuss the benefits of having a good night's sleep for body weight stability. Experimental studies have shown that short-term partial sleep restriction decreases glucose tolerance, increases sympathetic tone, elevates cortisol concentrations, decreases the satiety hormone leptin, increases the appetite-stimulating hormone ghrelin, and increases hunger and appetite. Short sleep duration might increase the risk of becoming obese, because it does not allow the recovery of a hormonal profile facilitating appetite control. Lack of sleep could also lead to weight gain and obesity by increasing the time available for eating and by making the maintenance of a healthy lifestyle more difficult. Furthermore, the increased fatigue and tiredness associated with sleeping too little could lessen one's resolve to follow exercise regimens. Short sleep duration appears to be a novel and independent risk factor for obesity. With the growing prevalence of chronic sleep restriction, any causal association between reduced sleep and obesity would have substantial importance from a public health standpoint. Future research is needed to determine whether sleep extension in sleep-deprived obese individuals will influence appetite control and/or reduce the amount of body fat.

  13. Uptake of Optional Activities Leads to Improved Performance in a Biomedical Sciences Class

    Science.gov (United States)

    Verkade, Heather; Lim, Saw Hoon

    2015-01-01

    Optional (non-assessed) learning activities are a learning tool that may help students achieve their desired grade, or help students with lower levels of previous experience in the topic. This study examines the implementation of, and outcomes from, two optional activities, one online and one paper-based. The activities complemented the lectures…

  14. The TECS model leads to active use of technology in home care

    DEFF Research Database (Denmark)

    Jensen, Ulla Gars; Skov, Hanne

    2017-01-01

    language to exchange experiences and share knowledge about the iPad as a work tool. Use of the iPad in patients’ homes led to new habits and routines. Nurses acquired relational expertise, implying active use of technology. The results show the importance of focusing on and funding reflection......Digitization in healthcare is accelerating worldwide. This article focuses on the X-Changery development project involving home-care nurses and their use of the iPad as a new tool in patients’ homes. The goal of the project was to bring knowledge from recent research on technological literacy...... in working life back to a work setting, thus giving nurses new technology competencies with the aim of enhancing their professionalism through the use of the iPad as a work tool. Through field observations, learning labs and focus-group interviews we can see that X-Changery gave home-care nurses a common...

  15. Rhabdomyolysis-Associated Mutations in Human LPIN1 Lead to Loss of Phosphatidic Acid Phosphohydrolase Activity.

    Science.gov (United States)

    Schweitzer, George G; Collier, Sara L; Chen, Zhouji; Eaton, James M; Connolly, Anne M; Bucelli, Robert C; Pestronk, Alan; Harris, Thurl E; Finck, Brian N

    2015-01-01

    Rhabdomyolysis is an acute syndrome due to extensive injury of skeletal muscle. Recurrent rhabdomyolysis is often caused by inborn errors in intermediary metabolism, and recent work has suggested that mutations in the human gene encoding lipin 1 (LPIN1) may be a common cause of recurrent rhabdomyolysis in children. Lipin 1 dephosphorylates phosphatidic acid to form diacylglycerol (phosphatidic acid phosphohydrolase; PAP) and acts as a transcriptional regulatory protein to control metabolic gene expression. Herein, a 3-year-old boy with severe recurrent rhabdomyolysis was determined to be a compound heterozygote for a novel c.1904T>C (p.Leu635Pro) substitution and a previously reported genomic deletion of exons 18-19 (E766-S838_del) in LPIN1. Western blotting with patient muscle biopsy lysates demonstrated a marked reduction in lipin 1 protein, while immunohistochemical staining for lipin 1 showed abnormal subcellular localization. We cloned cDNAs to express recombinant lipin 1 proteins harboring pathogenic mutations and showed that the E766-S838_del allele was not expressed at the RNA or protein level. Lipin 1 p.Leu635Pro was expressed, but the protein was less stable, was aggregated in the cytosol, and was targeted for proteosomal degradation. Another pathogenic single amino acid substitution, lipin 1 p.Arg725His, was well expressed and retained its transcriptional regulatory function. However, both p.Leu635Pro and p.Arg725His proteins were found to be deficient in PAP activity. Kinetic analyses demonstrated a loss of catalysis rather than diminished substrate binding. These data suggest that loss of lipin 1-mediated PAP activity may be involved in the pathogenesis of rhabdomyolysis in lipin 1 deficiency.

  16. Atypical presentation of a hormonally active adrenocortical tumor in an adolescent leading to delayed diagnosis.

    Science.gov (United States)

    Hagemann, Kerstin; Zanolari Calderari, Maura; Perren, Aurel; Cree, Ian; Mullis, Primus E; Flück, Christa E

    2011-01-01

    Adrenocortical tumors are rare in children and present with variable signs depending on the type of hormone excess. We herein describe the unusual presentation of a child with adrenocortical tumor and introduce the concept of in vitro chemosensitivity testing. A 10.5-year-old girl presented with hypertrichosis/hirsutism and weight loss. The weight loss and behavioral problems, associated with halted puberty and growth, led to the initial diagnosis of anorexia nervosa. However, subsequent weight gain but persisting arrest in growth and puberty and the appearance of central fat distribution prompted further evaluation. RESULTS AND FOLLOW-UP: 24h-urine free cortisol was elevated. Morning plasma ACTH was undetectable, while cortisol was elevated and circadian rhythmicity was absent. Thus a hormonally active adrenal cortical tumor (ACT) was suspected. On magnetic resonance imaging (MRI) a unilateral, encapsulated tumor was found which was subsequently removed surgically. Tissue was investigated histologically and for chemosensitivity in primary cell cultures. Although there were some risk factors for malignancy, the tumor was found to be a typical adenoma. Despite this histology, tumor cells survived in culture and were sensitive to cisplatin in combination with gemcitabine or paclitaxel. At surgery, the patient was started on hydrocortisone replacement which was unsuccessfully tapered over 3 months. Full recovery of the hypothalamus-pituitary-adrenal axis occurred only after 3 years. The diagnosis of a hormonally active adrenocortical tumor is often delayed because of atypical presentation. Cortisol replacement following unilateral tumor excision is mandatory and may be required for months or years. Individualized chemosensitivity studies carried out on primary cultures established from the tumor tissue itself may provide a tool in evaluating the effectiveness of chemotherapeutic drugs in the event that the adrenocortical tumor may prove to be carcinoma.

  17. To Lead or Not to Lead?

    Science.gov (United States)

    Bertenshaw, Maria; Bradford, Katie; Burns, Natalie; Flux, Rachel; Horan, Danielle

    2013-01-01

    The authors of this article, as student teachers, explored becoming facilitators in lessons focusing on micro-organisms. They elicited ideas from their students and found that even the brightest children held some misconceptions about micro-organisms. The students had some knowledge, but they had not learned how to apply this to investigations…

  18. 75 FR 78264 - Agency Information Collection Activities: Form N-336, Revision to an Existing Information...

    Science.gov (United States)

    2010-12-15

    ... SECURITY U.S. Citizenship and Immigration Services Agency Information Collection Activities: Form N-336... collection under review: Form N- 336, Request for Hearing on a Decision in Naturalization Proceedings Under Section 336; OMB Control No. 1615-0050. On August 18, 2010, USCIS published a 60-day notice in the Federal...

  19. A control architecture to coordinate distributed generators and active power filters coexisting in a microgrid

    DEFF Research Database (Denmark)

    Hashempour, Mohammad M.; Savaghebi, Mehdi; Quintero, Juan Carlos Vasquez

    2016-01-01

    This paper proposes a control architecture of distributed generators (DGs) inverters and shunt active power filters (APFs) in microgrids to compensate voltage harmonics in a coordinated way. For this, a hierarchical control structure is proposed that includes two control levels. The primary (local...

  20. A Control Architecture to Coordinate Distributed Generators and Active Power Filters Coexisting in a Microgrid

    DEFF Research Database (Denmark)

    Hashempour, Mohammad M.; Firoozabadi, Mehdi Savaghebi; Quintero, Juan Carlos Vasquez

    2016-01-01

    This paper proposes a control architecture of distributed generators (DGs) inverters and shunt active power filters (APFs) in microgrids to compensate voltage harmonics in a coordinated way. For this, a hierarchical control structure is proposed that includes two control levels. The primary (local...

  1. Early resumption of physical activities leads to inferior clinical outcomes after matrix-based autologous chondrocyte implantation in the knee.

    Science.gov (United States)

    Niethammer, Thomas R; Müller, Peter E; Safi, Elem; Ficklscherer, Andreas; Roßbach, Björn P; Jansson, Volkmar; Pietschmann, Matthias F

    2014-06-01

    Matrix-based autologous chondrocyte implantation is a well-established operation procedure for full cartilage defects. When to resume physical activity after matrix-based autologous chondrocyte implantation is controversial. Our hypothesis was that early resumption of physical activity leads to a worse clinical outcome after matrix-based autologous chondrocyte implantation in the knee two years post-operatively. Physical activity is defined as any kind of impact sport. Forty-four patients with cartilage defects of the knee were treated with matrix-based autologous chondrocyte implantation (Novocart3D). All patients were assessed preoperatively and after a period of 24 months with the University of California Los Angeles (UCLA) Activity score. The return to physical activities or sports after matrix-based autologous chondrocyte implantation was documented. Patients were evaluated using the International Knee Documentation Committee Knee Examination Form and visual analogue scale for pain after 6, 12 and 24 months. Fifty-five percent showed an unchanged level of physical activity in the UCLA Activity score post-operatively. About 35% showed a lower level and 10% a higher level of physical activity. The average return to physical activities or sports after matrix-based autologous chondrocyte implantation procedure was 10.2 months. Patients with a later return of sports after 12 months showed significantly better clinical results after two years. In particular, patients who started practicing impact sport after 12 months post-operatively showed significantly better results. Resuming physical activity including impact sports without waiting at least 12 months after the operation leads to inferior outcomes up to 24 months after matrix-based autologous chondrocyte implantation. Level IV.

  2. Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism

    DEFF Research Database (Denmark)

    Södersten, Erik; Feyder, Michael; Lerdrup, Mads

    2014-01-01

    Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2....... Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation....... The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p...

  3. An Activity Theory Approach to Analyze Barriers to a Virtual Management Information Systems (MIS) Curriculum

    Science.gov (United States)

    Jaradat, Suhair; Qablan, Ahmad; Barham, Areej

    2011-01-01

    This paper explains how the activity theory is used as a framework to analyze the barriers to a virtual Management Information Stream (MIS) Curriculum in Jordanian schools, from both the sociocultural and pedagogical perspectives. Taking the activity system as a unit of analysis, this study documents the processes by which activities shape and are…

  4. Does Seeking e-Cigarette Information Lead to Vaping? Evidence from a National Longitudinal Survey of Youth and Young Adults.

    Science.gov (United States)

    Yang, Qinghua; Liu, Jiaying; Lochbuehler, Kirsten; Hornik, Robert

    2017-12-13

    Youth and young adults (YYAs) are vulnerable populations for e-cigarette use or vaping. This study examined the effect of YYAs' health information seeking behavior (HISB) around e-cigarette use and vaping on their subsequent vaping behavior. We conducted a nationally representative longitudinal phone survey of 13-25 year olds from June 2014 to September 2016, with 2,413 respondents who completed a baseline and follow-up survey six months later. The results from lagged logistic regressions and mediation analyses showed a) that information seeking predicted higher likelihood of vaping six months later even after controlling for baseline smoking and vaping status, intention to vape, and demographics, and b) that information seeking partially mediated the relationship between intention to vape and subsequent vaping behavior. Theoretical and regulatory implications are discussed.

  5. THE RELEVANCE OF ACCOUNTING INFORMATION GENERATED BY THE APPLICATION OF IAS 29 RELATED TO SHAREHOLDERS CAPITAL

    Directory of Open Access Journals (Sweden)

    Bunget Ovidiu Constantin

    2013-07-01

    The objective of IAS 29 is to establish specific standards for entities reporting in the currency of a hyperinflationary economy, so that the financial information provided is meaningful. Our empirical analysis encompasses a hyperinflationary economy covering a wide variety of hyperinflationary conditions.

  6. When 'fit' leads to fit, and when 'fit' leads to fat: how message framing and intrinsic vs. extrinsic exercise outcomes interact in promoting physical activity.

    Science.gov (United States)

    Gallagher, Kristel M; Updegraff, John A

    2011-07-01

    A unique aspect of exercise is that people may choose to engage in it to achieve a variety of outcomes, ranging from extrinsic (appearance, health) to intrinsic (satisfaction, enjoyment). We examined how the impact of gain- vs. loss-framed messages depends on the type of outcome emphasised. Drawing from regulatory focus theory (Higgins, E.T. (1997). Beyond pleasure and pain. American Psychologist, 52, 1280-1300; Higgins, E.T. (2000). Making a good decision: Value from fit. American Psychologist, 55, 1217-1230), we predicted that gain-framed messages would 'fit' with intrinsic outcomes and loss-framed messages would 'fit' with extrinsic outcomes, but the effect of such fit on physical activity would depend on the participants' need for cognition (NC). We tested these hypotheses with a sample of 176 sedentary young adults who read an exercise message with randomly assigned frame (gain/loss) and outcome (intrinsic/extrinsic). Participants provided daily reports of exercise over the following week. The predicted interaction between frame, outcome and NC was found (p=0.001) such that a 'fit' message promoted somewhat, but not significantly, greater exercise for those with high NC, but a 'non-fit' message promoted significantly greater exercise for those with low NC. Furthermore, differences in physical activity were partially mediated by attitudes towards exercise. Findings shed light on how the outcomes and motivations associated with physical activity shape people's behavioural responses to framed health communications. © 2011 Taylor & Francis

  7. Fabrication Processes to Generate Concentration Gradients in Polymer Solar Cell Active Layers

    Science.gov (United States)

    Inaba, Shusei; Vohra, Varun

    2017-01-01

    Polymer solar cells (PSCs) are considered as one of the most promising low-cost alternatives for renewable energy production with devices now reaching power conversion efficiencies (PCEs) above the milestone value of 10%. These enhanced performances were achieved by developing new electron-donor (ED) and electron-acceptor (EA) materials as well as finding the adequate morphologies in either bulk heterojunction or sequentially deposited active layers. In particular, producing adequate vertical concentration gradients with higher concentrations of ED and EA close to the anode and cathode, respectively, results in an improved charge collection and consequently higher photovoltaic parameters such as the fill factor. In this review, we relate processes to generate active layers with ED–EA vertical concentration gradients. After summarizing the formation of such concentration gradients in single layer active layers through processes such as annealing or additives, we will verify that sequential deposition of multilayered active layers can be an efficient approach to remarkably increase the fill factor and PCE of PSCs. In fact, applying this challenging approach to fabricate inverted architecture PSCs has the potential to generate low-cost, high efficiency and stable devices, which may revolutionize worldwide energy demand and/or help develop next generation devices such as semi-transparent photovoltaic windows. PMID:28772878

  8. Hierarchical Coordinated Control of Distributed Generators and Active Power Filters to Enhance Power Quality of Microgrids

    DEFF Research Database (Denmark)

    Savaghebi, Mehdi; Hashempour, Mohammad M.; Guerrero, Josep M.

    2014-01-01

    This paper addresses the coordinated control of distributed generators (DGs) inverters and active power filters (APFs) to compensate voltage harmonics in microgrids. For this, a hierarchical control system is proposed to mitigate voltage harmonic distortion. The hierarchical control structure...... includes two control levels: primary control and secondary control. Primary control consists of power controllers, selective virtual impedance loops and proportional-resonant (PR) voltage/current controllers. Secondary control manages the compensation of voltage harmonic distortion of sensitive load bus...

  9. Picornavirus infection leading to immunosuppression

    OpenAIRE

    Cusick, Matthew F; Libbey, Jane E.; Fujinami, Robert S.

    2014-01-01

    Viruses, such as HIV, hepatitis A, poliovirus, coxsackievirus B3 and foot-and-mouth disease virus, use a variety of mechanisms to suppress the human immune system in order to evade clearance by the host. Therefore, investigating how a few changes in the viral genome of a nonlethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. In addition, we propose that gaining a better insight into how ...

  10. An Ethanol Extract of Artemisia iwayomogi Activates PPARδ Leading to Activation of Fatty Acid Oxidation in Skeletal Muscle

    Science.gov (United States)

    Cho, Si Young; Jeong, Hyun Woo; Sohn, Jong Hee; Seo, Dae-Bang; Kim, Wan Gi; Lee, Sang-Jun

    2012-01-01

    Although Artemisia iwayomogi (AI) has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI) was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ) using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1) and pyruvate dehydrogenase kinase isozyme 4 (PDK4), and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity. PMID:22479450

  11. An ethanol extract of Artemisia iwayomogi activates PPARδ leading to activation of fatty acid oxidation in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Si Young Cho

    Full Text Available Although Artemisia iwayomogi (AI has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1 and pyruvate dehydrogenase kinase isozyme 4 (PDK4, and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity.

  12. Activity based protein profiling leads to identification of novel protein targets for nerve agent VX

    NARCIS (Netherlands)

    Carmany, D.; Walz, A.J.; Hsu, F.L.; Benton, B.; Burnett, D.; Gibbons, J.; Noort, D.; Glaros, T.; Sekowski, J.W.

    2017-01-01

    Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and

  13. Generation of active protein phosphatase 2A is coupled to holoenzyme assembly.

    Directory of Open Access Journals (Sweden)

    Hans Hombauer

    2007-06-01

    Full Text Available Protein phosphatase 2A (PP2A is a prime example of the multisubunit architecture of protein serine/threonine phosphatases. Until substrate-specific PP2A holoenzymes assemble, a constitutively active, but nonspecific, catalytic C subunit would constitute a risk to the cell. While it has been assumed that the severe proliferation impairment of yeast lacking the structural PP2A subunit, TPD3, is due to the unrestricted activity of the C subunit, we recently obtained evidence for the existence of the C subunit in a low-activity conformation that requires the RRD/PTPA proteins for the switch into the active conformation. To study whether and how maturation of the C subunit is coupled with holoenzyme assembly, we analyzed PP2A biogenesis in yeast. Here we show that the generation of the catalytically active C subunit depends on the physical and functional interaction between RRD2 and the structural subunit, TPD3. The phenotype of the tpd3Delta strain is therefore caused by impaired, rather than increased, PP2A activity. TPD3/RRD2-dependent C subunit maturation is under the surveillance of the PP2A methylesterase, PPE1, which upon malfunction of PP2A biogenesis, prevents premature generation of the active C subunit and holoenzyme assembly by counteracting the untimely methylation of the C subunit. We propose a novel model of PP2A biogenesis in which a tightly controlled activation cascade protects cells from untargeted activity of the free catalytic PP2A subunit.

  14. Identification of intrinsic catalytic activity for electrochemical reduction of water molecules to generate hydrogen

    KAUST Repository

    Shinagawa, Tatsuya

    2015-01-01

    Insufficient hydronium ion activities at near-neutral pH and under unbuffered conditions induce diffusion-limited currents for hydrogen evolution, followed by a reaction with water molecules to generate hydrogen at elevated potentials. The observed constant current behaviors at near neutral pH reflect the intrinsic electrocatalytic reactivity of the metal electrodes for water reduction. This journal is © the Owner Societies.

  15. Partnership with informal education learning centers to develop hands-on activities for research outreach efforts

    Science.gov (United States)

    Courville, Z.; Haynes, R.; DeFrancis, G.; Koh, S.; Ringelberg, D.

    2012-12-01

    Outreach informed by scientific research plays an important role in fostering interest in science by making science and scientists accessible, fun, and interesting. Developing an interest in science in young, elementary-aged students through outreach is a rewarding endeavor for researchers, in that audiences are usually receptive, requirements for broader impacts are met, and bonds are formed between researchers and members of their local and surrounding communities. Promoting such interest among young students is imperative not only for an individual researcher's own self interest, but also for the strength of American science and innovation moving forward, and is the responsibility of the current generation of scientists. Developing genuine and successful inquiry-based, hands-on activities for elementary-aged students is outside the expertise of many researchers. Partnering with an informal education learning center (i.e. science museum or after-school program) provides researchers with the expertise they might be lacking in such endeavors. Here, we present a series of polar-, engineering- and microbiology-themed hands-on activities that have been developed by researchers at a government lab in partnership with a local science museum. Through a series of workshops, the science education staff at the museum provided researchers with background and instruction on inquiry and hands-on activities, and then collaborated with the researchers to develop activities which were later demonstrated at the museum to museum-goers. Education staff provided feedback about the presentation of the activities for further refinement. The program provided an opportunity for researchers to develop fun, on-target and age-appropriate science activities for elementary-aged students, an audience for outreach, and enabled general public audiences the chance to interact with researchers and scientists in an informal setting.

  16. Active Cascade Screening in Primary Inherited Arrhythmia Syndromes : Does It Lead to Prophylactic Treatment?

    NARCIS (Netherlands)

    Hofman, Nynke; Tan, Hanno L.; Alders, Marielle; van Langen, Irene M.; Wilde, Arthur A.M.

    2010-01-01

    Objectives: The purpose of this study was to investigate the follow-up and treatment of the mutation-carrying relatives of a proband with an inherited arrhythmia syndrome. Background: The congenital long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada

  17. Loss of ATM kinase activity leads to embryonic lethality in mice

    DEFF Research Database (Denmark)

    Daniel, J.A.; Pellegrini, M.; Filsuf, D.

    2012-01-01

    Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine wh...

  18. PileLine: a toolbox to handle genome position information in next-generation sequencing studies

    Directory of Open Access Journals (Sweden)

    Fdez-Riverola Florentino

    2011-01-01

    Full Text Available Abstract Background Genomic position (GP files currently used in next-generation sequencing (NGS studies are always difficult to manipulate due to their huge size and the lack of appropriate tools to properly manage them. The structure of these flat files is based on representing one line per position that has been covered by at least one aligned read, imposing significant restrictions from a computational performance perspective. Results PileLine implements a flexible command-line toolkit providing specific support to the management, filtering, comparison and annotation of GP files produced by NGS experiments. PileLine tools are coded in Java and run on both UNIX (Linux, Mac OS and Windows platforms. The set of tools comprising PileLine are designed to be memory efficient by performing fast seek on-disk operations over sorted GP files. Conclusions Our novel toolbox has been extensively tested taking into consideration performance issues. It is publicly available at http://sourceforge.net/projects/pilelinetools under the GNU LGPL license. Full documentation including common use cases and guided analysis workflows is available at http://sing.ei.uvigo.es/pileline.

  19. Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina

    Directory of Open Access Journals (Sweden)

    Sandra M. Cardona

    2015-10-01

    Full Text Available Fractalkine (CX3CL1 or FKN is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor CX3CR1 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of CX3CR1 in inflammatory-mediated damage to retinal neurons using a model of diabetic retinopathy. For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and diabetic (Ins2Akita CX3CR1-wild-type and CX3CR1-deficient mice at 10 and 20 weeks of age. Our results show that Ins2Akita CX3CR1-knockout mice exhibited (a decreased neuronal cell counts in the retinal ganglion cell layer, (b increased microglial cell numbers, and (c decreased astrocyte responses comparable with Ins2Akita CX3CR1-Wild-type mice at 20 weeks of age. Analyses of the inflammatory response using PCR arrays showed several inflammatory genes differentially regulated in diabetic tissues. From those, the response in Ins2Akita CX3CR1-deficient mice at 10 weeks of age revealed a significant upregulation of IL-1β at the transcript level that was confirmed by enzyme-linked immunosorbent assay in soluble retinal extracts. Overall, IL-1β, VEGF, and nitrite levels as a read out of nitric oxide production were abundant in Ins2Akita CX3CR1-deficient retina. Notably, double immunofluorescence staining shows that astrocytes act as a source of IL-1β in the Ins2Akita retina, and CX3CR1-deficient microglia potentiate the inflammatory response via IL-1β release. Collectively, these data demonstrate that dysregulated microglial responses in absence of CX3CR1 contribute to inflammatory-mediated damage of neurons in the diabetic retina.

  20. Evaluation of combined toxicity of phenols and lead to Photobacterium phosphoreum and quantitative structure-activity relationships.

    Science.gov (United States)

    Su, L M; Zhao, Y H; Yuan, X; Mu, C F; Wang, N; Yan, J C

    2010-03-01

    The combined toxicity of lead (Pb) and nine phenols were measured. The result indicated that the combined toxicity is not only dependent on the Pb concentrations but also on the positions of substituted groups of phenols. Quantitative structure-activity relationship equations were built from the combined toxicity and physico-chemical descriptors of phenols in the different Pb concentrations. The combined toxicity was related to water solubility and the third order molecular connectivity index ((3)X) in low Pb concentration, to solute excess molar refractivity (E) and ionization constant (pKa) in medium Pb concentration and to dipolarity/polarizability (S) in high Pb concentration.

  1. Dye surface coating enables visible light activation of TiO2 nanoparticles leading to degradation of neighboring biological structures.

    Science.gov (United States)

    Blatnik, Jay; Luebke, Lanette; Simonet, Stephanie; Nelson, Megan; Price, Race; Leek, Rachael; Zeng, Leyong; Wu, Aiguo; Brown, Eric

    2012-02-01

    Biologically and chemically modified nanoparticles are gaining much attention as a new tool in cancer detection and treatment. Herein, we demonstrate that an alizarin red S (ARS) dye coating on TiO2 nanoparticles enables visible light activation of the nanoparticles leading to degradation of neighboring biological structures through localized production of reactive oxygen species. Successful coating of nanoparticles with dye is demonstrated through sedimentation, spectrophotometry, and gel electrophoresis techniques. Using gel electrophoresis, we demonstrate that visible light activation of dye-TiO2 nanoparticles leads to degradation of plasmid DNA in vitro. Alterations in integrity and distribution of nuclear membrane associated proteins were detected via fluorescence confocal microscopy in HeLa cells exposed to perinuclear localized ARS-TiO2 nanoparticles that were photoactivated with visible light. This study expands upon previous studies that indicated dye coatings on TiO2 nanoparticles can serve to enhance imaging, by clearly showing that dye coatings on TiO2 nanoparticles can also enhance the photoreactivity of TiO2 nanoparticles by allowing visible light activation. The findings of our study suggest a therapeutic application of dye-coated TiO2 nanoparticles in cancer research; however, at the same time they may reveal limitations on the use of dye assisted visualization of TiO2 nanoparticles in live-cell imaging.

  2. Work-In-Progress Peer Consult on EPA's Multimedia Exposure Analysis to Inform a Public Health-Based Value for Lead in Drinking Water

    Science.gov (United States)

    This document is a compilation of responses from four external peer reviewers on EPA's "Multimedia Exposure Analysis to Inform a Public Health-Based Value for Lead in Drinking Water." It was delivered by Versar, Inc. under contract number EP-C-12-045 Task Order 91.

  3. p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation.

    Science.gov (United States)

    Jin, Huan; Yin, Shutao; Song, Xinhua; Zhang, Enxiang; Fan, Lihong; Hu, Hongbo

    2016-04-13

    Patulin is a major mycotoxin found in fungal contaminated fruits and their derivative products. Previous studies showed that patulin was able to induce increase of reactive oxygen species (ROS) generation and oxidative stress was suggested to play a pivotal role in patulin-induced multiple toxic signaling. The objective of the present study was to investigate the functional role of p53 in patulin-induced oxidative stress. Our study demonstrated that higher levels of ROS generation and DNA damage were induced in wild-type p53 cell lines than that found in either knockdown or knockout p53 cell lines in response to patulin exposure, suggesting p53 activation contributed to patulin-induced ROS generation. Mechanistically, we revealed that the pro-oxidant role of p53 in response to patulin was attributed to its ability to suppress catalase activity through up-regulation of PIG3. Moreover, these in vitro findings were further validated in the p53 wild-type/knockout mouse model. To the best of our knowledge, this is the first report addressing the functional role of p53 in patulin-induced oxidative stress. The findings of the present study provided novel insights into understanding mechanisms behind oxidative stress in response to patulin exposure.

  4. Can multi-generational exposure to ocean warming and acidification lead to the adaptation of life history and physiology in a marine metazoan?

    Science.gov (United States)

    Gibbin, Emma M; Chakravarti, Leela J; Jarrold, Michael D; Christen, Felix; Turpin, Vincent; Massamba N'Siala, Gloria; Blier, Pierre U; Calosi, Piero

    2017-02-15

    Ocean warming and acidification are concomitant global drivers that are currently threatening the survival of marine organisms. How species will respond to these changes depends on their capacity for plastic and adaptive responses. Little is known about the mechanisms that govern plasticity and adaptability or how global changes will influence these relationships across multiple generations. Here, we exposed the emerging model marine polychaete Ophryotrocha labronica to conditions simulating ocean warming and acidification, in isolation and in combination over five generations to identify: (i) how multiple versus single global change drivers alter both juvenile and adult life-history traits; (ii) the mechanistic link between adult physiological and fitness-related life-history traits; and (iii) whether the phenotypic changes observed over multiple generations are of plastic and/or adaptive origin. Two juvenile (developmental rate; survival to sexual maturity) and two adult (average reproductive body size; fecundity) life-history traits were measured in each generation, in addition to three physiological (cellular reactive oxygen species content, mitochondrial density, mitochondrial capacity) traits. We found that multi-generational exposure to warming alone caused an increase in juvenile developmental rate, reactive oxygen species production and mitochondrial density, decreases in average reproductive body size and fecundity, and fluctuations in mitochondrial capacity, relative to control conditions. Exposure to ocean acidification alone had only minor effects on juvenile developmental rate. Remarkably, when both drivers of global change were present, only mitochondrial capacity was significantly affected, suggesting that ocean warming and acidification act as opposing vectors of stress across multiple generations. © 2017. Published by The Company of Biologists Ltd.

  5. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

    Directory of Open Access Journals (Sweden)

    Paulo M F Cunha

    2010-07-01

    Full Text Available Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2 or the zinc-finger transcription factor lame duck (lmd lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  6. Factors that cause industries to lead or lag in use of information technology: does health care lag?

    Science.gov (United States)

    Minard, B

    1999-11-01

    The rate of diffusion of information technology varies among industries, as does its resultant added value. The different paces of work transformation are determined by the opportunities of the differing work processes, efficiency of exchange of workplace ideas, and relationships among constituencies. The differences raise the question of why the maturation process is accelerated (or restrained) in different industries, how the health care industry fares in comparison, and how information technology may be more effectively used as health care evolves toward new forms of work interaction, control mechanisms, and information technology management paradigms and as information processing moves toward higher levels of complexity.

  7. Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study

    Science.gov (United States)

    Arif, Hussain; Rehmani, Nida; Farhan, Mohd; Ahmad, Aamir; Hadi, Sheikh Mumtaz

    2015-01-01

    Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources) induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure–activity relationship of myricetin (MN), fisetin (FN), quercetin (QN), kaempferol (KL) and galangin (GN). Using single cell alkaline gel electrophoresis (comet assay), we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids. PMID:26569217

  8. Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study

    Directory of Open Access Journals (Sweden)

    Hussain Arif

    2015-11-01

    Full Text Available Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure–activity relationship of myricetin (MN, fisetin (FN, quercetin (QN, kaempferol (KL and galangin (GN. Using single cell alkaline gel electrophoresis (comet assay, we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids.

  9. Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study.

    Science.gov (United States)

    Arif, Hussain; Rehmani, Nida; Farhan, Mohd; Ahmad, Aamir; Hadi, Sheikh Mumtaz

    2015-11-09

    Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources) induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure-activity relationship of myricetin (MN), fisetin (FN), quercetin (QN), kaempferol (KL) and galangin (GN). Using single cell alkaline gel electrophoresis (comet assay), we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids.

  10. You and me, how (in-)active are we? The potential of sharing physical activity information to increase motivation

    NARCIS (Netherlands)

    Van Wijngaarden, J.; Van Halteren, A.T.

    2009-01-01

    This report describes the theoretical background and development of an application to share physical activity information, as well as the results of a four-week field study in which people shared physical activity information as measured by the Philips Activity Monitor. The existing web-service

  11. Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

    Directory of Open Access Journals (Sweden)

    Sarah E. Mondello

    2014-02-01

    Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

  12. 77 FR 74667 - Agency Information Collection Activities; Proposed Collection; Comment Request; Information To...

    Science.gov (United States)

    2012-12-17

    .... 360j(m)) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), the FDA is authorized to exempt a... condition that affects fewer than 4,000 individuals in the United States; (2) would not be available to a... Act ( http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCAct...

  13. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  14. 78 FR 70308 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-11-25

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities: Submission to OMB for Review and Approval; Public Comment Request AGENCY: Health Resources and Services... Act of 1995, the Health Resources and Services Administration (HRSA) has submitted an Information...

  15. 78 FR 41404 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-10

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities; Submission to OMB for Review and Approval; Public Comment Request AGENCY: Health Resources and Services... Act of 1995, the Health Resources and Services Administration (HRSA) has submitted an Information...

  16. 78 FR 41410 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-10

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities; Submission to OMB for Review and Approval; Public Comment Request AGENCY: Health Resources and Services... Act of 1995, the Health Resources and Services Administration (HRSA) has submitted an Information...

  17. Unintentional activation of translation equivalents in bilinguals leads to attention capture in a cross-modal visual task.

    Science.gov (United States)

    Singh, Niharika; Mishra, Ramesh Kumar

    2015-01-01

    Using a variant of the visual world eye tracking paradigm, we examined if language non-selective activation of translation equivalents leads to attention capture and distraction in a visual task in bilinguals. High and low proficient Hindi-English speaking bilinguals were instructed to programme a saccade towards a line drawing which changed colour among other distractor objects. A spoken word, irrelevant to the main task, was presented before the colour change. On critical trials, one of the line drawings was a phonologically related word of the translation equivalent of the spoken word. Results showed that saccade latency was significantly higher towards the target in the presence of this cross-linguistic translation competitor compared to when the display contained completely unrelated objects. Participants were also slower when the display contained the referent of the spoken word among the distractors. However, the bilingual groups did not differ with regard to the interference effect observed. These findings suggest that spoken words activates translation equivalent which bias attention leading to interference in goal directed action in the visual domain.

  18. Unintentional activation of translation equivalents in bilinguals leads to attention capture in a cross-modal visual task.

    Directory of Open Access Journals (Sweden)

    Niharika Singh

    Full Text Available Using a variant of the visual world eye tracking paradigm, we examined if language non-selective activation of translation equivalents leads to attention capture and distraction in a visual task in bilinguals. High and low proficient Hindi-English speaking bilinguals were instructed to programme a saccade towards a line drawing which changed colour among other distractor objects. A spoken word, irrelevant to the main task, was presented before the colour change. On critical trials, one of the line drawings was a phonologically related word of the translation equivalent of the spoken word. Results showed that saccade latency was significantly higher towards the target in the presence of this cross-linguistic translation competitor compared to when the display contained completely unrelated objects. Participants were also slower when the display contained the referent of the spoken word among the distractors. However, the bilingual groups did not differ with regard to the interference effect observed. These findings suggest that spoken words activates translation equivalent which bias attention leading to interference in goal directed action in the visual domain.

  19. The AGAAAAGA palindrome in PrP is required to generate a productive PrPSc-PrPC complex that leads to prion propagation.

    Science.gov (United States)

    Norstrom, Eric M; Mastrianni, James A

    2005-07-22

    The molecular hallmark of prion disease is the conversion of normal prion protein (PrPC) to an insoluble, proteinase K-resistant, pathogenic isoform (PrPSc). Once generated, PrPSc propagates by complexing with, and transferring its pathogenic conformation onto, PrPC. Defining the specific nature of this PrPSc-PrPC interaction is critical to understanding prion genesis. To begin to approach this question, we employed a prion-infected neuroblastoma cell line (ScN2a) combined with a heterologous yeast expression system to independently model PrPSc generation and propagation. We additionally applied fluorescence resonance energy transfer analysis to the latter to specifically study PrP-PrP interactions. In this report we focus on an N-terminal hydrophobic palindrome of PrP (112-AGAAAAGA-119) thought to feature intimately in prion generation via an unclear mechanism. We found that, in contrast to wild type (wt) PrP, PrP lacking the palindrome (PrPDelta112-119) neither converted to PrPSc when expressed in ScN2a cells nor generated proteinase K-resistant PrP when expressed in yeast. Furthermore, PrPDelta112-119 was a dominant-negative inhibitor of wtPrP in ScN2a cells. Both wtPrP and PrPDelta112-119 were highly insoluble when expressed in yeast and produced distinct cytosolic aggregates when expressed as fluorescent fusion proteins (PrP::YFP). Although self-aggregation was evident, fluorescence resonance energy transfer studies in live yeast co-expressing PrPSc-like protein and PrPDelta112-119 indicated altered interaction properties. These results suggest that the palindrome is required, not only for the attainment of the PrPSc conformation but also to facilitate the proper association of PrPSc with PrPC to effect prion propagation.

  20. Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells.

    Science.gov (United States)

    Rhein, V; Baysang, G; Rao, S; Meier, F; Bonert, A; Müller-Spahn, F; Eckert, A

    2009-09-01

    Evidence suggests that amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Here we investigated the specific effects of Abeta on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes I-IV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble Abeta protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise.

  1. Mapping epidemiology's past to inform its future: metaknowledge analysis of epidemiologic topics in leading journals, 1974-2013.

    Science.gov (United States)

    Trinquart, Ludovic; Galea, Sandro

    2015-07-15

    An empiric perspective on what epidemiology has studied over time might inform discussions about future directions for the discipline. We aimed to identify the main areas of epidemiologic inquiry and determine how they evolved over time in 5 high-impact epidemiologic journals. We analyzed the titles and abstracts of 20,895 articles that were published between 1974 and 2013. In 5 time periods that reflected approximately equal numbers of articles, we identified the main topics by clustering terms based on co-occurrence. Infectious disease and cardiovascular disease epidemiology were the prevailing topics over the 5 periods. Cancer epidemiology was a major topic from 1974 to 2001 but disappeared thereafter. Nutritional epidemiology gained relative importance from 1974 to 2013. Environmental epidemiology appeared during 1996-2001 and continued to be important, whereas 2 clusters related to methodology and meta-analysis in genetics appeared during 2008-2013. Several areas of epidemiology, including injury or psychiatric epidemiology, did not make an appearance as major topics at any time. In an ancillary analysis of 6 high-impact general medicine journals, we found patterns of epidemiologic articles that were overall consistent with the findings in epidemiologic journals. This metaknowledge investigation allowed identification of the dominant topics in and conversely those that were absent from 5 major epidemiologic journals. We discuss implications for the field. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. From "Scuba Diving" to "Jet Skiing"? Information Behavior, Political Science, and the Google Generation

    Science.gov (United States)

    Thornton, Stephen

    2010-01-01

    It is often suggested that the swift arrival of a world shaped by information superabundance--symbolized by the astonishing growth in popularity of the digital search engine Google--has changed the manner in which many learn. A particular concern of some is the perception that younger people have turned away from books and long articles and have…

  3. Coronary Sinus Lead Removal: A Comparison between Active and Passive Fixation Leads.

    Science.gov (United States)

    Pecha, Simon; Kennergren, Charles; Yildirim, Yalin; Gosau, Nils; Aydin, Ali; Willems, Stephan; Treede, Hendrik; Reichenspurner, Hermann; Hakmi, Samer

    2016-01-01

    Implantation of coronary sinus (CS) leads may be a difficult procedure due to different vein anatomies and a possible lead dislodgement. The mode of CS lead fixation has changed and developed in recent years. We compared the removal procedures of active and passive fixation leads. Between January 2009 and January 2014, 22 patients at our centre underwent CS lead removal, 6 active and 16 passive fixation leads were attempted using simple traction or lead locking devices with or without laser extraction sheaths. Data on procedural variables and success rates were collected and retrospectively analyzed. The mean patient age was 67.2 ± 9.8 years, and 90.9% were male. The indication for lead removal was infection in all cases. All active fixation leads were Medtronic® Attain StarFix™ Model 4195 (Medtronic Inc., Minneapolis, MN, USA). The mean time from implantation for the active and passive fixation leads was 9.9 ± 11.7 months (range 1.0-30.1) and 48.7 ± 33.6 months (range 5.7-106.4), respectively (p = 0.012). Only 3 of 6 StarFix leads were successfully removed (50%) compared to 16 of 16 (100%) of the passive fixation CS leads (p = 0.013). No death or complications occurred during the 30-day follow-up. According to our experience, removal of the Starfix active fixation CS leads had a higher procedural failure rate compared to passive.

  4. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion

    Science.gov (United States)

    Fauconnier, Jérémy; Meli, Albano C.; Thireau, Jérôme; Roberge, Stephanie; Shan, Jian; Sassi, Yassine; Reiken, Steven R.; Rauzier, Jean-Michel; Marchand, Alexandre; Chauvier, David; Cassan, Cécile; Crozier, Christine; Bideaux, Patrice; Lompré, Anne-Marie; Jacotot, Etienne; Marks, Andrew R.; Lacampagne, Alain

    2011-01-01

    Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion of infracted heart has been an important objective of strategies to improve outcomes. However, cardiac ischemia/reperfusion (I/R) is characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at the cellular level, disturbance in Ca2+ and redox homeostasis. In this study, we sought to determine how acute inflammatory response contributes to reperfusion injury and Ca2+ homeostasis disturbance after acute ischemia. Using a rat model of I/R, we show that circulating levels of TNF-α and cardiac caspase-8 activity were increased within 6 h of reperfusion, leading to myocardial nitric oxide and mitochondrial ROS production. At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca2+ leak. Pharmacological inhibition of caspase-8 before reperfusion with Q-LETD-OPh or prevention of calstabin2 depletion from the RyR2 complex with the Ca2+ channel stabilizer S107 (“rycal”) inhibited the SR Ca2+ leak, reduced ventricular arrhythmias, infarct size, and left ventricular remodeling after 15 d of reperfusion. TNF-α–induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca2+ leak trough normalization of RyR2 function is cardioprotective. PMID:21788490

  5. Forest inventories generate scientifically sound information on the forest resource, but do our data and information really matter?

    Science.gov (United States)

    Christoph Keinn; Goran Stahl

    2009-01-01

    Current research in forest inventory focuses very much on technical-statistical problems geared mainly to the optimization of data collection and information generation. The basic assumption is that better information leads to better decisions and, therefore, to better forest management and forest policy. Not many studies, however, strive to explicitly establish the...

  6. 76 FR 73019 - Proposed Information Collection (Agreement To Train on the Job Disabled Veterans) Activity...

    Science.gov (United States)

    2011-11-28

    ... AFFAIRS Proposed Information Collection (Agreement To Train on the Job Disabled Veterans) Activity... comments on information needed to assure that on the job training establishments are providing veterans... use of other forms of information technology. Title: Agreement to Train on the Job Disabled Veterans...

  7. Information Literacy Standards and the Politics of Knowledge Production: Using User-Generated Content to Incorporate Critical Pedagogy

    OpenAIRE

    Seale, Maura

    2010-01-01

    The ACRL Information Literacy Competency Standards remain the prevailing means of understanding information literacy, particularly within higher education. There is undoubtedly value in a clearly articulated and institutionalized conceptualization of information literacy, but the Standards are inadequate, incomplete, and inculcate complacency. The careful use of user-generated content in information literacy instruction offers a means of addressing gaps as well as incorporating antiracist, fe...

  8. Methylglyoxal-induced AMPK activation leads to autophagic degradation of thioredoxin 1 and glyoxalase 2 in HT22 nerve cells.

    Science.gov (United States)

    Dafre, Alcir Luiz; Schmitz, Ariana Ern; Maher, Pamela

    2017-07-01

    Methylglyoxal (MGO) is a major glycating agent that reacts with basic residues of proteins and promotes the formation of advanced glycation end products which are believed to play key roles in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. We previously showed that MGO treatment targets the thioredoxin and the glyoxalase systems, leading to a decrease in Trx1 and Glo2 proteins in immortalized mouse hippocampal HT22 nerve cells. Here, we propose that autophagy is the underlying mechanism leading to Glo2 and Trx1 loss induced by MGO. The autophagic markers p62, and the lipidated and active form of LC3, were increased by MGO (0.5mM). Autophagy inhibition with bafilomycin or chloroquine prevented the decrease in Trx1 and Glo2 at 6 and 18h after MGO treatment. Proteasome inhibition by MG132 exacerbated the effect of MGO on Trx1 and Glo2 degradation (18h), further suggesting a role for autophagy. ATG5 small interfering RNA protected Trx1 and Glo2 from MGO-induced degradation, confirming Trx1 and Glo2 loss is mediated by autophagy. In the search for the signals that control autophagy, we found that AMPK activation, a known autophagy inducer, was markedly increased by MGO treatment. AMPK activation was confirmed by increased acetyl coenzyme A carboxylase phosphorylation, a direct AMPK substrate and by decreased mTOR phosphorylation, an indirect marker of AMPK activation. To confirm that MGO-mediated Trx1 and Glo2 degradation was AMPK-dependent, AMPK-deficient mouse embryonic fibroblasts (MEFs) were treated with MGO. Wildtype MEFs presented the expected decrease in Trx1 and Glo2, while MGO was ineffective in decreasing these proteins in AMPK-deficient cells. Overall, the data indicate that MGO activates autophagy in an AMPK-dependent manner, and that autophagy was responsible for Trx1 and Glo2 degradation, confirming that Trx1 and Glo2 are molecular targets of MGO. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 76 FR 40454 - Proposed Information Collection (VSO Access to VHA Electronic Health Records) Activity; Comment...

    Science.gov (United States)

    2011-07-08

    ... AFFAIRS Proposed Information Collection (VSO Access to VHA Electronic Health Records) Activity; Comment... attorney by veterans who have medical information recorded in VHA electronic health records system... techniques or the use of other forms of information technology. Title: VSO Access to VHA Electronic Health...

  10. Beyond IgE—When Do IgE-Crosslinking and Effector Cell Activation Lead to Clinical Anaphylaxis?

    Directory of Open Access Journals (Sweden)

    Lars K. Poulsen

    2017-08-01

    Full Text Available Anaphylaxis in humans is inherently difficult to study due to the acuteness of symptoms and the lack of biomarkers serving as risk predictors. Most cases are related to IgE sensitizations to foods, insect venoms, and drugs with mastocytosis patients forming a smaller risk group. However, identifying the relatively small fraction of persons at risk has been exceedingly difficult. In this review, we propose to describe anaphylaxis in a broader context than defined by IgE sensitization alone. Exposure to a trigger, such as an allergen, may lead to anaphylaxis, but in particular, the internal dose sensed by the immune system needs to be established. Moreover, intrinsic patient factors as well as the specific circumstances of the exposure, i.e., the extrinsic factors, need to be thoroughly accounted for. More controversially, other triggers of anaphylaxis, such as increased sensitivity to or reduced catabolism of histamine (“histamine intolerance” or mast cell activation syndrome also named mast cell activation disorder have been suggested, but still with very limited epidemiological evidence that a significant proportion of the observed reactions are caused by these alleged conditions. Thus, when all conditions are considered, it seems as if IgE-mediated reactions are responsible for the vast majority of anaphylactic conditions.

  11. An Automated Approach to the Generation of Structured Building Information Models from Unstructured 3d Point Cloud Scans

    DEFF Research Database (Denmark)

    Tamke, Martin; Evers, Henrik Leander; Wessel, Raoul

    2016-01-01

    In this paper we present and evaluate an approach for the automatic generation of building models in IFC BIM format from unstructured Point Cloud scans, as they result from 3dlaser scans of buildings. While the actual measurement process is relatively fast, 85% of the overall time are spend...... on the interpretation and transformation of the resulting Point Cloud data into information, which can be used in architectural and engineering design workflows. Our approach to tackle this problem, is in contrast to existing ones which work on the levels of points, based on the detection of building elements...... design in BIM and simulations with the build environment....

  12. Expression of Activated Ras in Gastric Chief Cells of Mice Leads to the Full Spectrum of Metaplastic Lineage Transitions

    Science.gov (United States)

    Choi, Eunyoung; Hendley, Audrey M.; Bailey, Jennifer M.; Leach, Steven D.; Goldenring, James R.

    2015-01-01

    Background & Aims Gastric cancer develops in the context of parietal cell loss, spasmolytic polypeptide-expressing metaplasia (SPEM), and intestinal metaplasia (IM). We investigated whether expression of the activated form of Ras in gastric chief cells of mice leads to development of SPEM, as well as progression of metaplasia. Methods We studied Mist1-CreERT2Tg/+;LSL-K-Ras(G12D)Tg/+ (Mist1-Kras) mice, which express the active form of Kras in chief cells upon tamoxifen exposure. We studied Mist1-CreERT2Tg/+;LSL-KRas (G12D)Tg/+;R26RmTmG/+ (Mist1-Kras-mTmG) mice to examine whether chief cells that express active Kras give rise to SPEM and IM. Some mice received intraperitoneal injections of the MEK inhibitor, selumetinib, for 14 consecutive days. Gastric tissues were collected and analyzed by immunohistochemistry, immunofluorescence, and quantitative PCR. Results Mist1-Kras mice developed metaplastic glands, which completely replaced normal fundic lineages and progressed to IM within 3–4 months after tamoxifen injection. The metaplastic glands expressed markers of SPEM and IM, and were infiltrated by macrophages. Lineage tracing studies confirmed that the metaplasia developed directly from Kras (G12D)-induced chief cells. Selumetinib induced persistent regression of SPEM and IM and reestablished normal mucosal cells, which were derived from normal gastric progenitor cells. Conclusions Expression of activated Ras in chief cells of Mist1-Kras mice led to the full range of metaplastic lineage transitions, including SPEM and IM. Inhibition of Ras signaling by inhibition of MEK might reverse pre-neoplastic metaplasia in the stomach. PMID:26677984

  13. 32 CFR Appendix D to Part 169a - Commercial Activities Management Information System (CAMIS)

    Science.gov (United States)

    2010-07-01

    ... to Part 169a—Commercial Activities Management Information System (CAMIS) Each DoD Component shall... American Standard Code Information Interchange text file format on a MicroSoft-Disk Operating System... Schools) K—Defense Information Systems Agency (DISA) L—Defense Intelligence Agency M—United States Marine...

  14. Criteria to assess the quality of the Dutch Informal Pro-active Approach Model

    NARCIS (Netherlands)

    Marseille, A.T.; de Graaf, K.J.; Dragos, D.C.; Lafarge, F.

    2012-01-01

    If citizens in the Netherlands do not agree with a decision of a public authority, they can submit a written objection. The Informal Pro-active Approach Model (or “informal approach”) provides an alternative for the traditional conflict resolution procedures. This informal approach has led to a

  15. Reflecting on Earlier Experiences with Unsolicited Findings: Points to Consider for Next-Generation Sequencing and Informed Consent in Diagnostics

    Science.gov (United States)

    Rigter, Tessel; Henneman, Lidewij; Kristoffersson, Ulf; Hall, Alison; Yntema, Helger G; Borry, Pascal; Tönnies, Holger; Waisfisz, Quinten; Elting, Mariet W; Dondorp, Wybo J; Cornel, Martina C

    2013-01-01

    High-throughput nucleotide sequencing (often referred to as next-generation sequencing; NGS) is increasingly being chosen as a diagnostic tool for cases of expected but unresolved genetic origin. When exploring a higher number of genetic variants, there is a higher chance of detecting unsolicited findings. The consequential increased need for decisions on disclosure of these unsolicited findings poses a challenge for the informed consent procedure. This article discusses the ethical and practical dilemmas encountered when contemplating informed consent for NGS in diagnostics from a multidisciplinary point of view. By exploring recent similar experiences with unsolicited findings in other settings, an attempt is made to describe what can be learned so far for implementing NGS in standard genetic diagnostics. The article concludes with a set of points to consider in order to guide decision-making on the extent of return of results in relation to the mode of informed consent. We hereby aim to provide a sound basis for developing guidelines for optimizing the informed consent procedure. PMID:23784691

  16. Learning to Lead

    Science.gov (United States)

    Sindelar, Sarah

    2009-01-01

    When the author attended a leadership conference last year, she started to reflect on her own situation. In this article, the author reflects on her experience and her role as a library media specialist who wants to be a leader in her school. However, to be a leader in a school, one has to offer a set of skills and abilities that others aren't…

  17. Two Ways to Lead

    Science.gov (United States)

    Cody, Anthony

    2013-01-01

    One popular approach to teacher leadership is to identify certain teachers as particularly successful, then have others learn from them. Collaborative leadership, in contrast, looks at leadership as a quality that anyone can have. In this model, the goal is not to figure out who is best. Instead, teachers share their unique talents and interests…

  18. The Effect of Active Principles of Cilantro and Spirulina Powder on Lead Antagonism to Copper and Chromium in Carassius gibelio

    Directory of Open Access Journals (Sweden)

    Mărioara Nicula

    2017-11-01

    Full Text Available The goal of our work was to highlight the detoxifying potential of the active principles from lyophilized cilantro and spirulina in experimental contamination with lead, to Carassius gibelio, and their effect on lead antagonism to copper and chromium. 120 Prussian carps, weighing 22-25 g each were divided according to the following treatments for 21 days: C group (without treatment, E1 group (75 ppm Pb into water as Pb(NO32x ½H2O, E2 group (75 ppm Pb into water+2% lyophilized cilantro in feed, E3 group (75 ppm Pb into water+2% lyophilized spirulina in feed. At the end of the experimental period, tissue samples (gills, muscles myotome– epaxial, heart, skin and scales, intestine, liver, brain, gonads, kidney were collected after a starving for 12 hours, and fish euthanasia with clove oil. Determination of Cu and Cr concentration in biological samples was performed using atomic absorption spectrophotometer AAS-VARIAN. Pb addition into water in dose of 75 ppm, has resulted in Cu and Cr mobilization from fish tissues. Decreasing of Cu tissue level occurred less intensive in tissues sampled from groups receiving cilantro and spiriulina powder in feed, maximum efficiency in the counteracting the antagonism against Pb showing spirulina on the heart, liver, and kidney. Cr was maintained at relatively low values, although, cilantro powder has induced in some wise the Pb complexing. In contrast, the freeze-dried spirulina brought the tissue level of Cr close to that of the control group or even has determined its more efficient takeover from the feed.

  19. An Active RBSE Framework to Generate Optimal Stimulus Sequences in a BCI for Spelling

    Science.gov (United States)

    Moghadamfalahi, Mohammad; Akcakaya, Murat; Nezamfar, Hooman; Sourati, Jamshid; Erdogmus, Deniz

    2017-10-01

    A class of brain computer interfaces (BCIs) employs noninvasive recordings of electroencephalography (EEG) signals to enable users with severe speech and motor impairments to interact with their environment and social network. For example, EEG based BCIs for typing popularly utilize event related potentials (ERPs) for inference. Presentation paradigm design in current ERP-based letter by letter typing BCIs typically query the user with an arbitrary subset characters. However, the typing accuracy and also typing speed can potentially be enhanced with more informed subset selection and flash assignment. In this manuscript, we introduce the active recursive Bayesian state estimation (active-RBSE) framework for inference and sequence optimization. Prior to presentation in each iteration, rather than showing a subset of randomly selected characters, the developed framework optimally selects a subset based on a query function. Selected queries are made adaptively specialized for users during each intent detection. Through a simulation-based study, we assess the effect of active-RBSE on the performance of a language-model assisted typing BCI in terms of typing speed and accuracy. To provide a baseline for comparison, we also utilize standard presentation paradigms namely, row and column matrix presentation paradigm and also random rapid serial visual presentation paradigms. The results show that utilization of active-RBSE can enhance the online performance of the system, both in terms of typing accuracy and speed.

  20. Alternate reading frame protein (F protein) of hepatitis C virus: paradoxical effects of activation and apoptosis on human dendritic cells lead to stimulation of T cells.

    Science.gov (United States)

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

    2014-01-01

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

  1. Alternate reading frame protein (F protein of hepatitis C virus: paradoxical effects of activation and apoptosis on human dendritic cells lead to stimulation of T cells.

    Directory of Open Access Journals (Sweden)

    Subodh Kumar Samrat

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

  2. Does Structured Quizzing with Process Specific Feedback Lead to Learning Gains in an Active Learning Geoscience Classroom?

    Science.gov (United States)

    Palsole, S.; Serpa, L. F.

    2013-12-01

    There is a great realization that efficient teaching in the geosciences has the potential to have far reaching effects in outreach to decision and policy makers (Herbert, 2006; Manduca & Mogk, 2006). This research in turn informs educators that the geosciences by the virtue of their highly integrative nature play an important role in serving as an entry point into STEM disciplines and helping developing a new cadre of geoscientists, scientists and a general population with an understanding of science. Keeping these goals in mind we set to design introductory geoscience courses for non-majors and majors that move away from the traditional lecture models which don't necessarily contribute well to knowledge building and retention ((Handelsman et al., 2007; Hake, 1997) to a blended active learning classroom where basic concepts and didactic information is acquired online via webquests, lecturettes and virtual field trips and the face to face portions of the class are focused on problem solving exercises. The traditional way to ensure that students are prepared for the in-class activity is to have the students take a quiz online to demonstrate basic competency. In the process of redesign, we decided to leverage the technology to build quizzes that are highly structured and map to a process (formation of divergent boundaries for example) or sets of earth processes that we needed the students to know before in-class activities. The quizzes can be taken multiple times and provide process specific feedback, thus serving as a heuristic to the students to ensure they have acquired the necessary competency. The heuristic quizzes were developed and deployed over a year with the student data driving the redesign process to ensure synchronicity. Preliminary data analysis indicates a positive correlation between higher student scores on in-class application exercises and time spent on the process quizzes. An assessment of learning gains also indicate a higher degree of self

  3. Approach for Estimating Exposures and Incremental Health Effects from Lead Due to Renovation Repair and Painting Activities in Public and Commercial Buildings

    Science.gov (United States)

    Approach for Estimating Exposures and Incremental Health Effects from Lead Due to Renovation Repair and Painting Activities in Public and Commercial Buildings: links to documents at www.regulations.gov, links to PDFs related to Approach document

  4. Addition of DNA to Cr(VI) and cytochrome b5 containing proteoliposomes leads to generation of DNA strand breaks and Cr(III) complexes.

    Science.gov (United States)

    Borthiry, Griselda R; Antholine, William E; Myers, Judith M; Myers, Charles R

    2008-08-01

    Chromium (Cr) is a cytotoxic metal that can be associated with a variety of types of DNA damage, including Cr-DNA adducts and strand breaks. Prior studies with purified human cytochrome b(5) and NADPH:P450 reductase in reconstituted proteoliposomes (PLs) demonstrated rapid reduction of Cr(VI) (hexavalent chromium, as CrO(4)(2-), and the generation of Cr(V), superoxide (O(2)(*-)), and hydroxyl radical (HO(*)). Studies reported here examined the potential for the species produced by this system to interact with DNA. Strand breaks of purified plasmid DNA increased over time aerobically, but were not observed in the absence of O(2). Cr(V) is formed under both conditions, so the breaks are not mediated directly by Cr(V). The aerobic strand breaks were significantly prevented by catalase and EtOH, but not by the metal chelator diethylenetriaminepentaacetic acid (DTPA), suggesting that they are largely due to HO(*) from Cr-mediated redox cycling. EPR was used to assess the formation of Cr-DNA complexes. Following a 10-min incubation of PLs, CrO(4)(2-), and plasmid DNA, intense EPR signals at g=5.7 and g=5.0 were observed. These signals are attributed to specific Cr(III) complexes with large zero field splitting (ZFS). Without DNA, the signals in the g=5 region were weak. The large ZFS signals were not seen, when Cr(III)Cl(3) was incubated with DNA, suggesting that the Cr(III)-DNA interactions are different when generated by the PLs. After 24 h, a broad signal at g=2 is attributed to Cr(III) complexes with a small ZFS. This g=2 signal was observed without DNA, but it was different from that seen with plasmid. It is concluded that EPR can detect specific Cr(III) complexes that depend on the presence of plasmid DNA and the manner in which the Cr(III) is formed.

  5. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

    Directory of Open Access Journals (Sweden)

    Leticia Corrales

    2015-05-01

    Full Text Available Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic.

  6. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity.

    Science.gov (United States)

    Corrales, Leticia; Glickman, Laura Hix; McWhirter, Sarah M; Kanne, David B; Sivick, Kelsey E; Katibah, George E; Woo, Seng-Ryong; Lemmens, Edward; Banda, Tamara; Leong, Justin J; Metchette, Ken; Dubensky, Thomas W; Gajewski, Thomas F

    2015-05-19

    Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT) administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN) derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Active and Non-Active Volumetric Information Spaces to Supplement Traditional Rehabilitation

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2013-01-01

    The purpose of this paper is to inform on findings from a mature body of research titled SoundScapes. The goal was to define, create and question sensor-based ICT systems, techniques and methods to supplement traditional rehabilitation. Following initial biofeedback/sensorimotor tests, a noninvas......The purpose of this paper is to inform on findings from a mature body of research titled SoundScapes. The goal was to define, create and question sensor-based ICT systems, techniques and methods to supplement traditional rehabilitation. Following initial biofeedback/sensorimotor tests...

  8. Loss of NADH Oxidase Activity in Streptococcus mutans Leads to Rex-Mediated Overcompensation in NAD+ Regeneration by Lactate Dehydrogenase.

    Science.gov (United States)

    Baker, J L; Derr, A M; Faustoferri, R C; Quivey, R G

    2015-12-01

    Previous studies of the oral pathogen Streptococcus mutans have determined that this Gram-positive facultative anaerobe mounts robust responses to both acid and oxidative stresses. The water-forming NADH oxidase (Nox; encoded by nox) is thought to be critical for the regeneration of NAD(+), for use in glycolysis, and for the reduction of oxygen, thereby preventing the formation of damaging reactive oxygen species. In this study, the free NAD(+)/NADH ratio in a nox deletion strain (Δnox) was discovered to be remarkably higher than that in the parent strain, UA159, when the strains were grown in continuous culture. This unanticipated result was explained by significantly elevated lactate dehydrogenase (Ldh; encoded by ldh) activity and ldh transcription in the Δnox strain, which was mediated in part by the redox-sensing regulator Rex. cDNA microarray analysis of S. mutans cultures exposed to simultaneous acid stress (growth at a low pH) and oxidative stress (generated through the deletion of nox or the addition of exogenous oxygen) revealed a stress response synergistically heightened over that with either stress alone. In the Δnox strain, this elevated stress response included increased glucose phosphoenolpyruvate phosphotransferase system (PTS) activity, which appeared to be due to elevated manL transcription, mediated in part, like elevated ldh transcription, by Rex. While the Δnox strain does possess a membrane composition different from that of the parent strain, it did not appear to have defects in either membrane permeability or ATPase activity. However, the altered transcriptome and metabolome of the Δnox strain were sufficient to impair its ability to compete with commensal peroxigenic oral streptococci during growth under aerobic conditions. Streptococcus mutans is an oral pathogen whose ability to outcompete commensal oral streptococci is strongly linked to the formation of dental caries. Previous work has demonstrated that the S. mutans water

  9. Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency.

    Science.gov (United States)

    Bacchelli, Chiara; Moretti, Federico A; Carmo, Marlene; Adams, Stuart; Stanescu, Horia C; Pearce, Kerra; Madkaikar, Manisha; Gilmour, Kimberly C; Nicholas, Adeline K; Woods, C Geoffrey; Kleta, Robert; Beales, Phil L; Qasim, Waseem; Gaspar, H Bobby

    2017-02-01

    Signaling through the T-cell receptor (TCR) is critical for T-cell development and function. Linker for activation of T cells (LAT) is a transmembrane adaptor signaling molecule that is part of the TCR complex and essential for T-cell development, as demonstrated by LAT-deficient mice, which show a complete lack of peripheral T cells. We describe a pedigree affected by a severe combined immunodeficiency phenotype with absent T cells and normal B-cell and natural killer cell numbers. A novel homozygous frameshift mutation in the gene encoding for LAT was identified in this kindred. Genetic, molecular, and functional analyses were used to identify and characterize the LAT defect. Clinical and immunologic analysis of patients was also performed and reported. Homozygosity mapping was used to identify potential defective genes. Sanger sequencing of the LAT gene showed a mutation that resulted in a premature stop codon and protein truncation leading to complete loss of function and loss of expression of LAT in the affected family members. We also demonstrate loss of LAT expression and lack of TCR signaling restoration in LAT-deficient cell lines reconstituted with a synthetic LAT gene bearing this severe combined immunodeficiency mutation. For the first time, the results of this study show that inherited LAT deficiency should be considered in patients with combined immunodeficiency with T-cell abnormalities. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Mitotic defects lead to pervasive aneuploidy and accompany loss of RB1 activity in mouse LmnaDhe dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    C Herbert Pratt

    2011-03-01

    Full Text Available Lamin A (LMNA is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350 and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670. Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1 activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood.We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (Lmna(Dhe. We found that dermal fibroblasts from heterozygous Lmna(Dhe (Lmna(Dhe/+ mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, Lmna(Dhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3, a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1 also was perturbed in Lmna(Dhe/+ cells. Lmna(Dhe/+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects.These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control.

  11. Saturation mutagenesis of lysine 12 leads to the identification of derivatives of nisin A with enhanced antimicrobial activity.

    Directory of Open Access Journals (Sweden)

    Evelyn M Molloy

    Full Text Available It is becoming increasingly apparent that innovations from the "golden age" of antibiotics are becoming ineffective, resulting in a pressing need for novel therapeutics. The bacteriocin family of antimicrobial peptides has attracted much attention in recent years as a source of potential alternatives. The most intensively studied bacteriocin is nisin, a broad spectrum lantibiotic that inhibits gram-positive bacteria including important food pathogens and clinically relevant antibiotic resistant bacteria. Nisin is gene-encoded and, as such, is amenable to peptide bioengineering, facilitating the generation of novel derivatives that can be screened for desirable properties. It was to this end that we used a site-saturation mutagenesis approach to create a bank of producers of nisin A derivatives that differ with respect to the identity of residue 12 (normally lysine; K12. A number of these producers exhibited enhanced bioactivity and the nisin A K12A producer was deemed of greatest interest. Subsequent investigations with the purified antimicrobial highlighted the enhanced specific activity of this modified nisin against representative target strains from the genera Streptococcus, Bacillus, Lactococcus, Enterococcus and Staphylococcus.

  12. Saturation Mutagenesis of Lysine 12 Leads to the Identification of Derivatives of Nisin A with Enhanced Antimicrobial Activity

    Science.gov (United States)

    Molloy, Evelyn M.; Field, Des; Connor, Paula M. O'.; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

    2013-01-01

    It is becoming increasingly apparent that innovations from the “golden age” of antibiotics are becoming ineffective, resulting in a pressing need for novel therapeutics. The bacteriocin family of antimicrobial peptides has attracted much attention in recent years as a source of potential alternatives. The most intensively studied bacteriocin is nisin, a broad spectrum lantibiotic that inhibits Gram-positive bacteria including important food pathogens and clinically relevant antibiotic resistant bacteria. Nisin is gene-encoded and, as such, is amenable to peptide bioengineering, facilitating the generation of novel derivatives that can be screened for desirable properties. It was to this end that we used a site-saturation mutagenesis approach to create a bank of producers of nisin A derivatives that differ with respect to the identity of residue 12 (normally lysine; K12). A number of these producers exhibited enhanced bioactivity and the nisin A K12A producer was deemed of greatest interest. Subsequent investigations with the purified antimicrobial highlighted the enhanced specific activity of this modified nisin against representative target strains from the genera Streptococcus, Bacillus, Lactococcus, Enterococcus and Staphylococcus. PMID:23505531

  13. Active optics for next generation space telescopes

    Science.gov (United States)

    Costes, V.; Perret, L.; Laubier, D.; Delvit, J. M.; Imbert, C.; Cadiergues, L.; Faure, C.

    2017-09-01

    High resolution observation systems need bigger and bigger telescopes. The design of such telescopes is a key issue for the whole satellite. In order to improve the imaging resolution with minimum impact on the satellite, a big effort must be made to improve the telescope compactness. Compactness is also important for the agility of the satellite and for the size and cost of the launcher. This paper shows how compact a high resolution telescope can be. A diffraction limited telescope can be less than ten times shorter than its focal length. But the compactness impacts drastically the opto-mechanical sensitivity and the optical performances. Typically, a gain of a factor of 2 leads to a mechanical tolerance budget 6 times more difficult. The need to implement active optics for positioning requirements raises very quickly. Moreover, the capability to compensate shape defaults of the primary mirror is the way to simplify the mirror manufacture, to mitigate the development risks and to minimize the cost. The larger the primary mirror is, the more interesting it is to implement active optics for shape compensations. CNES is preparing next generation of earth observation satellite in the frame of OTOS (Observation de la Terre Optique Super-Résolue; High resolution earth observing optical system). OTOS is a technology program. In particular, optical technological developments and breadboards dedicated to active optics are on-going. The aim is to achieve TRL 5 to TRL6 for these new technologies and to validate the global performances of such an active telescope.

  14. Preferences for and barriers to formal and informal athletic training continuing education activities.

    Science.gov (United States)

    Armstrong, Kirk J; Weidner, Thomas G

    2011-01-01

    Our previous research determined the frequency of participation and perceived effect of formal and informal continuing education (CE) activities. However, actual preferences for and barriers to CE must be characterized. To determine the types of formal and informal CE activities preferred by athletic trainers (ATs) and barriers to their participation in these activities. Cross-sectional study. Athletic training practice settings. Of a geographically stratified random sample of 1000 ATs, 427 ATs (42.7%) completed the survey. As part of a larger study, the Survey of Formal and Informal Athletic Training Continuing Education Activities (FIATCEA) was developed and administered electronically. The FIATCEA consists of demographic characteristics and Likert scale items (1 = strongly disagree, 5 = strongly agree) about preferred CE activities and barriers to these activities. Internal consistency of survey items, as determined by Cronbach α, was 0.638 for preferred CE activities and 0.860 for barriers to these activities. Descriptive statistics were computed for all items. Differences between respondent demographic characteristics and preferred CE activities and barriers to these activities were determined via analysis of variance and dependent t tests. The α level was set at .05. Hands-on clinical workshops and professional networking were the preferred formal and informal CE activities, respectively. The most frequently reported barriers to formal CE were the cost of attending and travel distance, whereas the most frequently reported barriers to informal CE were personal and job-specific factors. Differences were noted between both the cost of CE and travel distance to CE and all other barriers to CE participation (F(1,411) = 233.54, P Informal CE was highly valued by ATs because it could be individualized.

  15. 77 FR 16831 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-03-22

    ... implement GHG emissions reductions strategies and review their progress towards meeting their reduction... AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment Request; Federal Supplier (Small Business) Greenhouse Gas Inventory Pilot (Renewal) AGENCY: Environmental...

  16. 78 FR 21118 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-04-09

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... includes all schools that are not supported primarily by public funds, that provide classroom instruction... Management Services, Office of Management. BILLING CODE 4000-01-P ...

  17. 76 FR 70127 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-11-10

    ... amount of carbon used for activated carbon injection and to calculate the estimated hourly carbon... Information and Regulatory Affairs, Office of Management and Budget (OMB), Attention: Desk Officer for EPA...

  18. 76 FR 56503 - Agency Information Collection Activity (VSO Access to VHA Electronic Health Records) Under OMB...

    Science.gov (United States)

    2011-09-13

    ... AFFAIRS Agency Information Collection Activity (VSO Access to VHA Electronic Health Records) Under OMB... INFORMATION: Title: VSO Access to VHA Electronic Health Records, VA Form 10- 0400. OMB Control Number: 2900... recorded in VHA electronic health records system. An agency may not conduct or sponsor, and a person is not...

  19. 78 FR 54636 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-09-05

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... necessary to the proper functions of the Department; (2) will this information be processed and used in a... recommendations of the National Research Council's reports on early childhood. Five key program reform areas...

  20. 78 FR 66344 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-11-05

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... to their performance in the classroom. The study will examine data from a teacher survey and data..., Information and Records Management Services, Office of Management. BILLING CODE 4000-01-P ...

  1. 78 FR 73864 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-12-09

    ..., agencies and offices have recent data and information to inform program and policy decision-making. Need..., ASPE conducts research and evaluation studies, develops policy analyses, and estimates the cost and benefits of policy alternatives for HHS related programs. The goal of developing these activities is to...

  2. A SUMO-regulated activation function controls synergy of c-Myb through a repressor–activator switch leading to differential p300 recruitment

    Science.gov (United States)

    Molværsmyr, Ann-Kristin; Sæther, Thomas; Gilfillan, Siv; Lorenzo, Petra Isabel; Kvaløy, Heidi; Matre, Vilborg; Gabrielsen, Odd Stokke

    2010-01-01

    Synergy between transcription factors operating together on complex promoters is a key aspect of gene activation. The ability of specific factors to synergize is restricted by sumoylation (synergy control, SC). Focusing on the haematopoietic transcription factor c-Myb, we found evidence for a strong SC linked to SUMO-conjugation in its negative regulatory domain (NRD), while AMV v-Myb has escaped this control. Mechanistic studies revealed a SUMO-dependent switch in the function of NRD. When NRD is sumoylated, the activity of c-Myb is reduced. When sumoylation is abolished, NRD switches into being activating, providing the factor with a second activation function (AF). Thus, c-Myb harbours two AFs, one that is constitutively active and one in the NRD being SUMO-regulated (SRAF). This double AF augments c-Myb synergy at compound natural promoters. A similar SUMO-dependent switch was observed in the regulatory domains of Sp3 and p53. We show that the change in synergy behaviour correlates with a SUMO-dependent differential recruitment of p300 and a corresponding local change in histone H3 and H4 acetylation. We therefore propose a general model for SUMO-mediated SC, where SUMO controls synergy by determining the number and strength of AFs associated with a promoter leading to differential chromatin signatures. PMID:20385574

  3. Relation of fatty acid composition in lead-exposed mallards to fat mobilization, lipid peroxidation and alkaline phosphatase activity

    Science.gov (United States)

    Mateo, R.; Beyer, W.N.; Spann, J.W.; Hoffman, D.J.

    2003-01-01

    The increase of n-6 polyunsaturated fatty acids (PUFA) in animal tissues has been proposed as a mechanism of lead (Pb) poisoning through lipid peroxidation or altered eicosanoids metabolism. We have studied fatty acid (FA) composition in liver and brain of mallards (Anas platyrhynchos) feeding for 3 weeks on diets containing combinations of low or high levels of vitamin E (20 or 200 UI/kg) and Pb (0 or 2 g/kg). Saturated FA, n-6 PUFA and total concentrations of FA were higher in livers of Pb-exposed mallards, but not in their brains. The percentage of n-6 PUFA in liver and brain was slightly higher in Pb-exposed mallards. The increase of n-6 PUFA in liver was associated with decreased triglycerides and increased cholesterol in plasma, thus could be in part attributed to feed refusal and fat mobilization. The hepatic ratios between adrenic acid (22:4 n-6) and arachidonic acid (20:4 n-6) or between adrenic acid and linoleic acid (18:2 n-6) were higher in Pb exposed birds, supporting the existing hypothesis of increased fatty acid elongation by Pb. Among the possible consequences of increased n-6 PUFA concentration in tissues, we found increased lipid peroxidation in liver without important histopathological changes, and decreased plasma alkaline phosphatase activity that may reflect altered bone metabolism in birds.

  4. Lead stress effects on physiobiochemical activities of higher plants.

    Science.gov (United States)

    Sengar, Rakesh Singh; Gautam, Madhu; Sengar, Rajesh Singh; Garg, Sanjay Kumar; Sengar, Kalpana; Chaudhary, Reshu

    2008-01-01

    Lead is a metallic pollutant emanating from various environmental sources including industrial wastes, combustion of fossil fuels, and use of agrochemicals. Lead may exist in the atmosphere as dusts, fumes, mists, and vapors, and in soil as a mineral. Soils along roadsides are rich in lead because vehicles burn leaded gasoline, which contributes to environmental lead pollution. Other important sources of lead pollution are geological weathering, industrial processing of ores and minerals, leaching of lead from solid wastes, and animal and human excreta. Lead is nondegradable, readily enters the food chain, and can subsequently endanger human and animal health. Lead is one of the most important environment pollutants and deserves the increasing attention it has received in recent decades. The present effort was undertaken to review lead stress effects on the physiobiochemical activity of higher plants. Lead has gained considerable attention as a potent heavy metal pollutant because of growing anthropogenic pressure on the environment. Lead-contaminated soils show a sharp decline in crop productivity. Lead is absorbed by plants mainly through the root system and in minor amounts through the leaves. Within the plants, lead accumulates primarily in roots, but some is translocated to aerial plant parts. Soil pH, soil particle size, cation-exchange capacity, as well as root surface area, root exudation, and mycorrhizal transpiration rate affect the availability and uptake of lead by plants. Only a limited amount of lead is translocated from roots to other organs because there are natural plant barriers in the root endodermis. At lethal concentrations, this barrier is broken and lead may enter vascular tissues. Lead in plants may form deposits of various sizes, present mainly in intercellular spaces, cell walls, and vacuoles. Small deposits of this metal are also seen in the endoplasmic reticulum, dictyosome, and dictyosome-derived vesicles. After entering the cells, lead

  5. Lead generation strategy as a multichannel mechanism of growth of a modern enterprise

    Directory of Open Access Journals (Sweden)

    Łukowski Wojciech

    2016-09-01

    Full Text Available Lead generation strategy describes the marketing process of involvement and capture of interest in a product or service which is aimed at developing sales plans and, as a consequence, soliciting new clients. Lead generation is becoming an increasingly popular demand-generating strategy, which – through its multichannelled dissemination of the generated message – gives it a much greater reach. Lead generation assists organisations in achieving a greater brand awareness, building relationships and attracting more potential clients to fill their sales pipeline. The primary purpose of this publication is identifying the possibilities that the implementation of lead generation strategies provides to modern enterprises. It discusses the key aspects of this issue, demonstrating how the significance of organisations change, how their value effectively increases as a result of the implementation of tools furnished by processes that form an integral part of lead generation. The article defines the factors and processes that affect the effective course of actions undertaken within lead generation campaigns.

  6. Lead users' ideas on core features to support physical activity in rheumatoid arthritis: a first step in the development of an internet service using participatory design.

    Science.gov (United States)

    Revenäs, Åsa; Opava, Christina H; Åsenlöf, Pernilla

    2014-03-22

    Despite the growing evidence of the benefits of physical activity (PA) in individuals with rheumatoid arthritis (RA), the majority is not physically active enough. An innovative strategy is to engage lead users in the development of PA interventions provided over the internet. The aim was to explore lead users' ideas and prioritization of core features in a future internet service targeting adoption and maintenance of healthy PA in people with RA. Six focus group interviews were performed with a purposively selected sample of 26 individuals with RA. Data were analyzed with qualitative content analysis and quantification of participants' prioritization of most important content. Six categories were identified as core features for a future internet service: up-to-date and evidence-based information and instructions, self-regulation tools, social interaction, personalized set-up, attractive design and content, and access to the internet service. The categories represented four themes, or core aspects, important to consider in the design of the future service: (1) content, (2) customized options, (3) user interface and (4) access and implementation. This is, to the best of our knowledge, the first study involving people with RA in the development of an internet service to support the adoption and maintenance of PA.Participants helped identifying core features and aspects important to consider and further explore during the next phase of development. We hypothesize that involvement of lead users will make transfer from theory to service more adequate and user-friendly and therefore will be an effective mean to facilitate PA behavior change.

  7. Periowave demonstrates bactericidal activity against periopathogens and leads to improved clinical outcomes in the treatment of adult periodontitis

    Science.gov (United States)

    Street, Cale N.; Andersen, Roger; Loebel, Nicolas G.

    2009-02-01

    Periodontitis affects half of the U.S. population over 50, and is the leading cause of tooth loss after 35. It is believed to be caused by growth of complex bacterial biofilms on the tooth surface below the gumline. Photodynamic therapy, a technology used commonly in antitumor applications, has more recently been shown to exhibit antimicrobial efficacy. We have demonstrated eradication of the periopathogens Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans in vitro using PeriowaveTM; a commercial photodisinfection system. In addition, several clinical studies have now demonstrated the efficacy of this treatment. A pilot study in the U.S. showed that 68% of patients treated with PeriowaveTM adjunctively to scaling and root planing (SRP) showed clinical attachment level increase of >1 mm, as opposed to 30% with SRP alone. In a subsequent larger study, a second PeriowaveTM treatment 6 weeks after initial treatment led to pocket depth improvements of >1.5 mm in 89% of patients. Finally, in the most recent multicenter, randomized, examiner-blinded study conducted on 121 subjects in Canada, PeriowaveTM treatment produced highly significant gains in attachment level (0.88 mm vs. 0.57 mm; p=0.003) and pocket depth (0.87 mm vs. 0.63 mm; p=0.01) as compared to SRP alone. In summary, PeriowaveTM demonstrated strong bactericidal activity against known periopathogens, and treatment of periodontitis using this system produced significantly better clinical outcomes than SRP alone. This, along with the absence of any adverse events in patients treated to date demonstrates that PDT is a safe and effective treatment for adult chronic periodontitis.

  8. 78 FR 68831 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-11-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... impact on intermediate outcomes in schools, including the schools data culture and data-informed...

  9. Using an Informal Cardiovascular System Activity to Study the Effectiveness of Science Education in Unexpected Places

    Science.gov (United States)

    Monzack, Elyssa Lynne; Zenner Petersen, Greta M.

    2011-01-01

    Venues for informal science education are usually those sought out by people who are specifically looking for an educational experience. Whether planning a trip to a museum or choosing a television program, these individuals are actively seeking an informal educational experience; they are a self-selected group. This paper investigates whether…

  10. 78 FR 42950 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-18

    ... innovative group support program that combines mindfulness-based stress reduction, nutrition, and physical... HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB for... reference. Information Collection Request Title: WHAM: Women's Health and Mindfulness Program. Abstract: The...

  11. 78 FR 57846 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-09-20

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review...-0793. Type of Review: Revision of an existing collection of information. Respondents/Affected Public... Postsecondary Education (FIPSE) programs: Comprehensive (84.116B), European Union-United States (84.116J), U.S...

  12. 78 FR 76310 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-12-17

    ... Department of Public Health and Human Services focuses on a community-based, client-centered clinical service... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... questions designed to gather information on successes and challenges associated with the program design and...

  13. 78 FR 54245 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-09-03

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... respondents, including through the use of information technology. Please note that written comments received..., TIMSS has also conducted an assessment of advanced mathematics and physics of students at the end of...

  14. 77 FR 30318 - Agency Information Collection Activities: 30-Day Notice of Intention To Request Clearance of...

    Science.gov (United States)

    2012-05-22

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF THE INTERIOR National Park Service Agency Information Collection Activities: 30-Day Notice of Intention To Request Clearance of Collection of Information; Opportunity for Public Comment AGENCY: National Park Service...

  15. 78 FR 41409 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-10

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... Act of 1995, the Health Resources and Services Administration (HRSA) has submitted an Information.... 254r, the Health Resources and Services Administration proposes to revise the State Offices of Rural...

  16. 78 FR 954 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-01-07

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35), the Health Resources and Services Administration (HRSA) will submit an Information Collection Request (ICR) to the Office...

  17. 78 FR 41409 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-10

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... Act of 1995, the Health Resources and Services Administration (HRSA) has submitted an Information... Resources and Services Administration (HRSA) plans to conduct a survey of eligible users of the National...

  18. 78 FR 14517 - Agency Information Collection Activities; Comment Request; Technical Assistance To Promote the...

    Science.gov (United States)

    2013-03-06

    ... for Out-of- School Youth.'' The information will be used by the Department of Education and its... Agency Information Collection Activities; Comment Request; Technical Assistance To Promote the Implementation of Re-Engagement Centers for Out-of-School Youth AGENCY: Office of Elementary and Secondary...

  19. 78 FR 51181 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-08-20

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... Centers for Out-of-School Youth AGENCY: Office of Elementary and Secondary Education (OESE), Department of.... chapter 3501 et seq.), ED is proposing a new information collection. DATES: Interested persons are invited...

  20. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

    Science.gov (United States)

    Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

    2009-11-26

    Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  1. Neutron Activation Foil and Thermoluminescent Dosimeter Responses to a Lead Reflected Pulse of the CEA Valduc SILENE Critical Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Thomas Martin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Celik, Cihangir [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Isbell, Kimberly McMahan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lee, Yi-kang [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Gagnier, Emmanuel [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Authier, Nicolas [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Piot, Jerome [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Jacquet, Xavier [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Rousseau, Guillaume [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Reynolds, Kevin H. [Y-12 National Security Complex, Oak Ridge, TN (United States)

    2016-09-01

    This benchmark experiment was conducted as a joint venture between the US Department of Energy (DOE) and the French Commissariat à l'Energie Atomique (CEA). Staff at the Oak Ridge National Laboratory (ORNL) in the US and the Centre de Valduc in France planned this experiment. The experiment was conducted on October 13, 2010 in the SILENE critical assembly facility at Valduc. Several other organizations contributed to this experiment and the subsequent evaluation, including CEA Saclay, Lawrence Livermore National Laboratory (LLNL), the Y-12 National Security Complex (NSC), Babcock International Group in the United Kingdom, and Los Alamos National Laboratory (LANL). The goal of this experiment was to measure neutron activation and thermoluminescent dosimeter (TLD) doses from a source similar to a fissile solution critical excursion. The resulting benchmark can be used for validation of computer codes and nuclear data libraries as required when performing analysis of criticality accident alarm systems (CAASs). A secondary goal of this experiment was to qualitatively test performance of two CAAS detectors similar to those currently and formerly in use in some US DOE facilities. The detectors tested were the CIDAS MkX and the Rocky Flats NCD-91. The CIDAS detects gammas with a Geiger-Muller tube, and the Rocky Flats detects neutrons via charged particles produced in a thin 6LiF disc, depositing energy in a Si solid-state detector. These detectors were being evaluated to determine whether they would alarm, so they were not expected to generate benchmark quality data.

  2. Cognitive tasks in information analysis: Use of event dwell time to characterize component activities

    Energy Technology Data Exchange (ETDEWEB)

    Sanquist, Thomas F.; Greitzer, Frank L.; Slavich, Antoinette L.; Littlefield, Rik J.; Littlefield, Janis S.; Cowley, Paula J.

    2004-09-28

    Technology-based enhancement of information analysis requires a detailed understanding of the cognitive tasks involved in the process. The information search and report production tasks of the information analysis process were investigated through evaluation of time-stamped workstation data gathered with custom software. Model tasks simulated the search and production activities, and a sample of actual analyst data were also evaluated. Task event durations were calculated on the basis of millisecond-level time stamps, and distributions were plotted for analysis. The data indicate that task event time shows a cyclic pattern of variation, with shorter event durations (< 2 sec) reflecting information search and filtering, and longer event durations (> 10 sec) reflecting information evaluation. Application of cognitive principles to the interpretation of task event time data provides a basis for developing “cognitive signatures” of complex activities, and can facilitate the development of technology aids for information intensive tasks.

  3. Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70

    Directory of Open Access Journals (Sweden)

    Bigalke Iris

    2007-04-01

    Full Text Available Abstract Background For optimal T cell activation it is desirable that dendritic cells (DCs display peptides within MHC molecules as signal 1, costimulatory molecules as signal 2 and, in addition, produce IL-12p70 as signal 3. IL-12p70 polarizes T cell responses towards CD4+ T helper 1 cells, which then support the development of CD8+ cytotoxic T lymphocytes. We therefore developed new maturation cocktails allowing DCs to produce biologically active IL-12p70 for large-scale cancer vaccine development. Methods After elutriation of leukapheresis products in a closed bag system, enriched monocytes were cultured with GM-CSF and IL-4 for six days to generate immature DCs that were then matured with cocktails, containing cytokines, interferon-gamma, prostaglandin E2, and a ligand for Toll-like receptor 8, with or without poly (I:C. Results Mature DCs expressed appropriate maturation markers and the lymph node homing chemokine receptor, CCR7. They retained full maturity after culture for two days without maturation cocktails and following cryopreservation. TLR ligand stimulation induced DCs capable of secreting IL-12p70 in primary cultures and after one day of coculture with CD40L-expressing fibroblasts, mimicking an encounter with T cells. DCs matured with our new cocktails containing TLR8 ligand, with or without poly (I:C, induced alloresponses and stimulated virus-specific T cells after peptide-pulsing. DCs matured in cocktails containing TLR8 ligand without poly (I:C could also be loaded with RNA as a source of antigen, whereas DCs matured in cocktails containing poly (I:C were unable to express proteins following RNA transfer by electroporation. Conclusion Our new maturation cocktails allowed easy DC harvesting, stable maturation and substantial recoveries of mature DCs after cryopreservation. Our procedure for generating DCs is easily adaptable for GMP-compliance and yields IL-12p70-secreting DCs suitable for development of cancer vaccines using

  4. p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation

    OpenAIRE

    Huan Jin; Shutao Yin; Xinhua Song; Enxiang Zhang; Lihong Fan; Hongbo Hu

    2016-01-01

    Patulin is a major mycotoxin found in fungal contaminated fruits and their derivative products. Previous studies showed that patulin was able to induce increase of reactive oxygen species (ROS) generation and oxidative stress was suggested to play a pivotal role in patulin-induced multiple toxic signaling. The objective of the present study was to investigate the functional role of p53 in patulin-induced oxidative stress. Our study demonstrated that higher levels of ROS generation and DNA dam...

  5. Cochrane Rapid Reviews Methods Group to play a leading role in guiding the production of informed high-quality, timely research evidence syntheses

    Directory of Open Access Journals (Sweden)

    Chantelle Garritty

    2016-10-01

    Full Text Available Abstract Background Policymakers and healthcare stakeholders are increasingly seeking evidence to inform the policymaking process, and often use existing or commissioned systematic reviews to inform decisions. However, the methodologies that make systematic reviews authoritative take time, typically 1 to 2 years to complete. Outside the traditional SR timeline, “rapid reviews” have emerged as an efficient tool to get evidence to decision-makers more quickly. However, the use of rapid reviews does present challenges. To date, there has been limited published empirical information about this approach to compiling evidence. Thus, it remains a poorly understood and ill-defined set of diverse methodologies with various labels. In recent years, the need to further explore rapid review methods, characteristics, and their use has been recognized by a growing network of healthcare researchers, policymakers, and organizations, several with ties to Cochrane, which is recognized as representing an international gold standard for high-quality, systematic reviews. Purpose In this commentary, we introduce the newly established Cochrane Rapid Reviews Methods Group developed to play a leading role in guiding the production of rapid reviews given they are increasingly employed as a research synthesis tool to support timely evidence-informed decision-making. We discuss how the group was formed and outline the group’s structure and remit. We also discuss the need to establish a more robust evidence base for rapid reviews in the published literature, and the importance of promoting registration of rapid review protocols in an effort to promote efficiency and transparency in research. Conclusion As with standard systematic reviews, the core principles of evidence-based synthesis should apply to rapid reviews in order to minimize bias to the extent possible. The Cochrane Rapid Reviews Methods Group will serve to establish a network of rapid review stakeholders

  6. Report on achievements in fiscal 1998. Development of technologies to put photovoltaic power generation systems into practical use (International cooperation project - collection of information on IEA photovoltaic power generation program); 1998 nendo taiyoko hatsuden system jitsuyoka gijutsu kaihatsu seika hokokusho. Kokusai kyoryoku jigyo (IEA taiyoko hatsuden program ni kansuru joho shushu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    Research and development, verification, analysis and information exchange have been performed based on the 'Treaty to Execute the Research and Cooperation Program on Photovoltaic Power Generation System'. The IEA/REWP/PVPS activities in fiscal 1999 include the participation to the two executive committee meetings (Valencia and Sydney), and the subcommittee activities. The subcommittee activities are as follows: Task I: information exchange on and proliferation of the photovoltaic power generation systems, Task II: operation performance and design of the photovoltaic power generation systems, Task III: design and operation of the independent type and the island use power plants, Task VII: Building integrated photovoltaic power generation systems, Task VI, Sub-task 5: investigations and researches on possibility for photovoltaic power generation systems utilizing unutilized lands including deserts, and Task IX: technical cooperation to expand photovoltaic power generation system markets. (NEDO)

  7. A Better Management Information System Is Needed to Promote Information Sharing, Effective Planning, and Coordination of Afghanistan Reconstruction Activities

    Science.gov (United States)

    2009-07-30

    management information systems for collecting data on their reconstruction activities, but there is no single management information system that provides...spreadsheets, presentations, and other ad hoc reports. An integrated management information system that provides a common operating picture of all U.S

  8. Extraction of chronically implanted coronary sinus leads active fixation vs passive fixation leads.

    Science.gov (United States)

    Crossley, George H; Sorrentino, Robert A; Exner, Derek V; Merliss, Andrew D; Tobias, Serge M; Martin, David O; Augostini, Ralph; Piccini, Jonathan P; Schaerf, Raymond; Li, Shelby; Miller, Clayton T; Adler, Stuart W

    2016-06-01

    The Medtronic model 4195 (StarFix) left ventricular lead is an active fixation lead that provides additional support within the coronary sinus (CS) via deployable lobes. While this lead has been shown to have excellent stability within the CS, concerns about its extractability have been raised. The aim of this study was to compare the safety and efficacy of the extraction of the model 4195 lead vs other Medtronic CS leads in a prospective cohort study. Patients undergoing extraction of this and other CS leads for standard indications were prospectively enrolled and studied. The primary outcomes of interest were the removal success rates and associated complication rates. Patients were followed for a month postprocedure. The overall left ventricular lead extraction success rate was 97.6% (n = 205). Among 40 patients with chronic model 4195 leads, there were 37 successful extractions (92.5%) as compared to 98.8% for the 165 non-4195 leads. However, in 2 of the 3 StarFix lead extraction failures, standard extraction techniques were not used. All 10 of the model 4195 leads that had been implanted for less than 6 months were extracted without incident. In this largest study of CS lead extractions published to date, the overall success rate of the extraction of chronically implanted CS leads is high and the complication rate is similar in these lead models. The extraction of the model 4195 lead is clearly more challenging, but it can be accomplished in high-volume extraction centers with experienced operators. It is recommended that the model 4195 lead be extracted by experienced operators. Copyright © 2016. Published by Elsevier Inc.

  9. Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells

    DEFF Research Database (Denmark)

    Llavero, Francisco; Urzelai, Bakarne; Osinalde, Nerea

    2015-01-01

    Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate in the sig...

  10. Anesthesia-related changes in information transfer may be caused by reduction in local information generation.

    Science.gov (United States)

    Wollstadt, Patricia; Sellers, Kristin K; Hutt, Axel; Frohlich, Flavio; Wibral, Michael

    2015-08-01

    In anesthesia research it is an open question how general anesthetics lead to loss of consciousness (LOC). It has been proposed that LOC may be caused by the disruption of cortical information processing, preventing information integration. Therefore, recent studies investigating information processing under anesthesia focused on changes in information transfer, measured by transfer entropy (TE). However, often this complex technique was not applied rigorously, using time series in symbolic representation, or using TE differences without accounting for neural conduction delays, or without accounting for signal history. Here, we used current best-practice in TE estimation to investigate information transfer under anesthesia: We conducted simultaneous recordings in primary visual cortex (V1) and prefrontal cortex (PFC) of head-fixed ferrets in a dark environment under different levels of anesthesia (awake, 0.5% isoflurane, 1.0 % isoflurane). To elucidate reasons for changes in TE, we further quantified information processing within brain areas by estimating active information storage (AIS) as an estimator of predictable information, and Lempel-Ziv complexity (LZC) as an estimator of signal entropy. Under anesthesia, we found a reduction in information transfer (TE) between PFC and V1 with a stronger reduction for the feedback direction (PFC to V1), validating previous results. Furthermore, entropy (LZC) was reduced and activity became more predictable as indicated by higher values of AIS. We conclude that higher anesthesia concentrations indeed lead to reduced inter-areal information transfer, which may be partly caused by decreases in local entropy and increases in local predictability. In revealing a possible reason for reduced TE that is potentially independent of inter-areal coupling, we demonstrate the value of directly quantifying information processing in addition to focusing on dynamic properties such as coupling strength.

  11. p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy

    NARCIS (Netherlands)

    Moreno-Smith, Myrthala; Lakoma, Anna; Chen, Zaowen; Tao, Ling; Scorsone, Kathleen A.; Schild, Linda; Aviles-Padilla, Kevin; Nikzad, Rana; Zhang, Yankai; Chakraborty, Rikhia; Molenaar, Jan J.; Vasudevan, Sanjeev A.; Sheehan, Vivien; Kim, Eugene S.; Paust, Silke; Shohet, Jason M.; Barbieri, Eveline

    2017-01-01

    Purpose: mTORC1 inhibitors are promising agents for neuroblastoma therapy; however, they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR

  12. Passive Reactive Berm to Provide Low Maintenance Lead Containment at Active Small Arms Firing Ranges: Field Demonstration

    Science.gov (United States)

    2012-08-01

    soils can potentially migrate off-site into sensitive environmental receptors (e.g., wetlands , surface-water bodies, groundwater supplies) through...conversion of relatively soluble/bioavailable forms of lead to relatively insoluble/less bioavailable pyromorphites (Pb5( PO4 )3X(s), where X= Cl-, F-, OH...efficiency of 37 to 100 percent can be achieved through the process of hydroxyapatite dissolution and hydroxypyromorphite [Pb10( PO4 )6(OH)2

  13. Human Connexin43E42K mutation from a sudden infant death victim leads to impaired ventricular activation and neonatal death in mice.

    Science.gov (United States)

    Lübkemeier, Indra; Bosen, Felicitas; Kim, Jung-Sun; Sasse, Philipp; Malan, Daniela; Fleischmann, Bernd K; Willecke, Klaus

    2015-02-01

    Sudden infant death syndrome (SIDS) describes the sudden, unexplained death of a baby during its first year of age and is the third leading cause of infant mortality. It is assumed that ≤20% of all SIDS cases are because of cardiac arrhythmias resulting from mutations in ion channel proteins. Besides ion channels also cardiac gap junction channels are important for proper conduction of cardiac electric activation. In the mammalian heart Connexin43 (Cx43) is the major gap junction protein expressed in ventricular cardiomyocytes. Recently, a novel Connexin43 loss-of-function mutation (Cx43E42K) was identified in a 2-month-old SIDS victim. We have generated Cx43E42K-expressing mice as a model for SIDS. Heterozygous cardiac-restricted Cx43E42K-mutated mice die neonatally without major cardiac morphological defects. Electrocardiographic recordings of embryonic Cx43+/E42K mice reveal severely disturbed ventricular activation, whereas immunohistochemical analyses show normal localization and expression patterns of gap junctional Connexin43 protein in the Cx43E42K-mutated newborn mouse heart. Because we did not find heterogeneous gap junction loss in Cx43E42K mouse hearts, we conclude that the Cx43E42K gap junction channel creates an arrhythmogenic substrate leading to lethal ventricular arrhythmias. The strong cardiac phenotype of Cx43E42K expressing mice supports the association between the human Cx43E42K mutation and SIDS and indicates that Connexin43 mutations should be considered in future studies when SIDS cases are to be molecularly explained. © 2014 American Heart Association, Inc.

  14. The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan

    DEFF Research Database (Denmark)

    Wickström, Malin; Viktorsson, Kristina; Lundholm, Lovisa

    2010-01-01

    and apoptotic signaling. In conclusion, this study demonstrates a role of APN in the activation of the melphalan prodrug J1 and subsequently, its cytotoxicity. Given that APN is shown to be overexpressed in several solid tumors our data suggest that J1 may be activated in a tumor selective manner....

  15. Monitoring the effects of exposure to lead and cadmium in working and living environment through standard biochemical blood parameters and liver endonucleases activity

    Directory of Open Access Journals (Sweden)

    Nikolić Ružica S.

    2011-01-01

    Full Text Available Heavy metals as pollutants in the working and living environment are a serious health and environmental problem because they are toxic, non-biodegradable, accumulate in living systems and have a long half-life in soil. Sources of lead contamination are combustion products in the chemical industry and metallurgy, industrial waste water, landfills, traffic etc. Lead enters into the body via the food chain and drinking water. In the body lead is deposited in the liver, kidneys, brain and mineral tissues. Excretion of lead causes damage to the epithelial cells of certain organs. High level exposure to cadmium is usually the result of environmental pollution by human activities. Exposure to cadmium can lead to acute and chronic tissue damage of various organs, including liver and kidneys in humans and in animals. In this paper we analyzed the effects of lead and cadmium exposure, in working and living environment, on the model system of experimental animals, particularly the activity of certain liver enzymes, acid and alkaline DNase, and standard biochemical blood parameters. The study showed that lead and cadmium significantly affect the protein content, red blood cells, hemoglobin and hematocrit, and the activity of liver enzymes. This harmful effect of this toxic metal can be reduced by the supplements.

  16. IFN-gamma secreted by CD103+ dendritic cells leads to IgG generation in the mesenteric lymph node in the absence of vitamin A.

    Science.gov (United States)

    Chang, Jae-Hoon; Cha, Hye-Ran; Chang, Sun-Young; Ko, Hyun-Jeong; Seo, Sang-Uk; Kweon, Mi-Na

    2011-06-15

    Although the induction mechanism of secretory IgA has been well studied, that of IgG in the mucosal compartments is not well understood. In this study, vitamin A deficiency was convincingly shown to be associated with increased IgG in serum and intestinal fluid. We found increased numbers of IgG-secreting B cells in the lamina propria of the small intestine and mesenteric lymph node (MLN) of vitamin A-deficient (VAD) mice. Of note, IFN-γ secreted by MLN dendritic cells (DCs) was significantly augmented in VAD mice, unlike control mice, and CD103(+) DCs were the main subsets to secrete IFN-γ. The aberrant increase of IgG in VAD mice can be ascribable to IFN-γ, because IFN-γ(-/-) VAD mice have normal IgG levels and the addition of rIFN-γ increased IgG production by B cells cocultured with MLN DCs from IFN-γ(-/-) VAD mice. Oral feeding of antibiotics resulted in significant reduction of IgG in VAD mice, indicating a critical role for altered commensal bacteria for IgG class-switching recombination in the absence of vitamin A. Collectively, vitamin A deficiency provokes the generation of IFN-γ-secreting CD103(+) DCs, which may be a critical regulator for IgG generation in the MLN.

  17. Socially-Informed Timeline Generation for Complex Events

    OpenAIRE

    Wang, Lu; Cardie, Claire; Marchetti, Galen

    2016-01-01

    Existing timeline generation systems for complex events consider only information from traditional media, ignoring the rich social context provided by user-generated content that reveals representative public interests or insightful opinions. We instead aim to generate socially-informed timelines that contain both news article summaries and selected user comments. We present an optimization framework designed to balance topical cohesion between the article and comment summaries along with the...

  18. Oxidative stress-induced JNK1/2 activation triggers proapoptotic signaling and apoptosis that leads to diabetic embryopathy.

    Science.gov (United States)

    Li, Xuezheng; Weng, Hongbo; Xu, Cheng; Reece, E Albert; Yang, Peixin

    2012-08-01

    Oxidative stress and apoptosis are implicated in the pathogenesis of diabetic embryopathy. The proapoptotic c-Jun NH(2)-terminal kinases (JNK)1/2 activation is associated with diabetic embryopathy. We sought to determine whether 1) hyperglycemia-induced oxidative stress is responsible for the activation of JNK1/2 signaling, 2) JNK1 contributes to the teratogenicity of hyperglycemia, and 3) both JNK1 and JNK2 activation cause activation of downstream transcription factors, caspase activation, and apoptosis, resulting in neural tube defects (NTDs). Wild-type (WT) embryos from nondiabetic WT dams and WT, superoxide dismutase (SOD)1-overexpressing, jnk1(+/-), jnk1(-/-), and jnk2(-/-) embryos exposed to maternal hyperglycemia were used to assess JNK1/2 activation, NTDs, activation of transcription factors downstream of JNK1/2, caspase cascade, and apoptosis. SOD1 overexpression abolished diabetes-induced activation of JNK1/2 and their downstream effectors: phosphorylation of c-Jun, activating transcription factor 2, and E twenty-six-like transcription factor 1 and dephosphorylation of forkhead box class O3a. jnk1(-/-) embryos had significantly lower incidences of NTDs than those of WT or jnk1(+/-) embryos. Either jnk1 or jnk2 gene deletion blocked diabetes-induced activation of JNK1/2 signaling, caspases 3 and 8, and apoptosis in Sox1(+) neural progenitors of the developing neural tube. Our results show that JNK1 and JNK2 are equally involved in diabetic embryopathy and that the oxidative stress-JNK1/2-caspase pathway mediates the proapoptotic signals and the teratogenicity of maternal diabetes.

  19. Brain activity related to working memory for temporal order and object information.

    Science.gov (United States)

    Roberts, Brooke M; Libby, Laura A; Inhoff, Marika C; Ranganath, Charan

    2017-06-08

    Maintaining items in an appropriate sequence is important for many daily activities; however, remarkably little is known about the neural basis of human temporal working memory. Prior work suggests that the prefrontal cortex (PFC) and medial temporal lobe (MTL), including the hippocampus, play a role in representing information about temporal order. The involvement of these areas in successful temporal working memory, however, is less clear. Additionally, it is unknown whether regions in the PFC and MTL support temporal working memory across different timescales, or at coarse or fine levels of temporal detail. To address these questions, participants were scanned while completing 3 working memory task conditions (Group, Position and Item) that were matched in terms of difficulty and the number of items to be actively maintained. Group and Position trials probed temporal working memory processes, requiring the maintenance of hierarchically organized coarse and fine temporal information, respectively. To isolate activation related to temporal working memory, Group and Position trials were contrasted against Item trials, which required detailed working memory maintenance of visual objects. Results revealed that working memory encoding and maintenance of temporal information relative to visual information was associated with increased activation in dorsolateral PFC (DLPFC), and perirhinal cortex (PRC). In contrast, maintenance of visual details relative to temporal information was characterized by greater activation of parahippocampal cortex (PHC), medial and anterior PFC, and retrosplenial cortex. In the hippocampus, a dissociation along the longitudinal axis was observed such that the anterior hippocampus was more active for working memory encoding and maintenance of visual detail information relative to temporal information, whereas the posterior hippocampus displayed the opposite effect. Posterior parietal cortex was the only region to show sensitivity to temporal

  20. Beyond IgE-When Do IgE-Crosslinking and Effector Cell Activation Lead to Clinical Anaphylaxis?

    DEFF Research Database (Denmark)

    Poulsen, Lars K; Jensen, Bettina M; Esteban, Vanesa

    2017-01-01

    , identifying the relatively small fraction of persons at risk has been exceedingly difficult. In this review, we propose to describe anaphylaxis in a broader context than defined by IgE sensitization alone. Exposure to a trigger, such as an allergen, may lead to anaphylaxis, but in particular, the internal...... dose sensed by the immune system needs to be established. Moreover, intrinsic patient factors as well as the specific circumstances of the exposure, i.e., the extrinsic factors, need to be thoroughly accounted for. More controversially, other triggers of anaphylaxis, such as increased sensitivity...

  1. Environmental lead hazard to children.

    Science.gov (United States)

    Mittal, S K

    1992-01-01

    Clinically evident lead poisoning is rare in Indian children but is more common than in adults. In children, lead poisoning may appear as fever, seizures, anemia, or abdominal pain, while in adults it is more likely to manifest as chronic minor peripheral neuropathy or gum pigmentation. Children with acute lead poisoning can be treated with chelators such as EDTA and BAL, but many are left with permanent brain damage. The most common sources of acute lead poisoning in Indian children are inhalation of fumes from burned car batteries, ingestion of flaking paint, consuming food cooked in cheap aluminum or brass utensils, and eating contaminated soil. The sources of chronic lead poisoning are water from lead pipes and fumes from industrial or automotive exhaust. Another common source in India is application of "kajjal" to children's eyes. Sources of lead in Western countries, such as drinking water, canned food, residential paint, automotive fuel, and ambient air quality, are regulated by law. None of these are regulated in India.

  2. 78 FR 51276 - Proposed Information Collection (Access to Care Dialysis Pilot Survey and Interview); Activity...

    Science.gov (United States)

    2013-08-20

    ... AFFAIRS Proposed Information Collection (Access to Care Dialysis Pilot Survey and Interview); Activity... improve access to dialysis care for Veterans. DATES: Written comments and recommendations on the proposed... refer to ``OMB Control No. 2900-NEW (Access to Care Dialysis Pilot Survey and Interview)'' in any...

  3. RESPIRATORY SYNCYTIAL VIRUS INFECTION RESULTS IN ACTIVATION OF MULTIPLE PROTEIN KINASE C ISOFORMS LEADING TO ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE. (R826711C001)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  4. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production

    NARCIS (Netherlands)

    Kauffman, HF; Tomee, JFC; van de Riet, MA; Timmerman, AJB; Borger, P

    Background: Proteases in extracts of Aspergillus fumigatus cause epithelial cell desquamation and release of proinflammatory cytokines. Objective: We sought to assess protease activity in Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus extracts and study the ability of these

  5. 76 FR 19090 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-04-06

    ..., except for small appliances and room air conditioners, be provided with a servicing aperture that... AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment... forwarded to the Office of Management and Budget (OMB) for review and approval. This is a request to renew...

  6. 75 FR 28803 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-05-24

    ..., precipitation, drinking water, and milk. Samples are sent to EPA's National Air and Radiation Environmental... according to medium being sampled: Milk, quarterly; drinking water, quarterly; rain (precipitation), as... Information Collection Activities; Submission to OMB for Review and Approval; Comment Request; RadNet (Renewal...

  7. Lead-elevated activity of xanthine oxidase in lead-exposed workers

    Directory of Open Access Journals (Sweden)

    Sławomir Kasperczyk

    2013-04-01

    Full Text Available Background: The aim of the present study was to explore the connection between lead toxicity and the activity of xanthine oxidase (XO. In addition, we indicated the uric acid (UA and creatinine levels and concentration of erythrocyte malondialdehyde (MDA to estimate oxidative stress intensity. Materials and Methods: The examined group consisted of 125 healthy male employees of zinc and lead works. The examined group was divided into tertiles according to blood lead levels. In the collected blood samples, concentrations of lead-exposure indices, UA, creatinine, and MDA as well as activity of XO were measured concomitantly. The control group consisted of 32 healthy male administrative workers who were exposed to lead only environmentally. Results: XO activity and MDA level were significantly elevated in all tertiles compared to the control group. Creatinine level was significantly elevated in the medium and high tertiles. However, the level of UA was significantly elevated in the high tertile, while in the low and medium tertile only a tendency toward higher values was observed. Conclusions: Occupational exposure to lead induces activity of XO. This induction may contribute to the observed simultaneously increased oxidative stress, measured as MDA level, and the increased level of UA. Med Pr 2013;64(2:175–180

  8. Lead

    Science.gov (United States)

    ... Test Safety Alert: Learn about CDC Recommendations Second Informational Call (CDC-RFA-17-1701PPHF17), April 5, 2017, ... CLPPP CAP Healthy Homes Assessment Tools Lead Health Literacy Initiative Refugee Tool Kit Resources Healthy Homes and ...

  9. Defects in the Expression of Chloroplast Proteins Leads to H2O2Accumulation and Activation of Cyclic Electron Flow around Photosystem I.

    Science.gov (United States)

    Strand, Deserah D; Livingston, Aaron K; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M; Fisher, Nicholas; Froehlich, John E; Cruz, Jeffrey A; Minhas, Deepika; Hixson, Kim K; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M

    2016-01-01

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 ( hcef2 ) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force ( pmf ), activation of the photoprotective q E response, and the accumulation of H 2 O 2 . Surprisingly, hcef2 was mapped to a non-sense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex, and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash-induced thylakoid electric field suggest that these defect lead to accumulation of H 2 O 2 in hcef2 , which we have previously shown leads to activation of NDH-related CEF. We observed similar increases in CEF, as well as increases in H 2 O 2 accumulation, in other translation defective mutants. This suggests that loss of coordination in plastid protein levels lead to imbalances in photosynthetic energy balance that leads to an increase in CEF. These results taken together with a large body of previous observations, support a general model in which processes that lead to imbalances in chloroplast energetics result in the production of H 2 O 2 , which in turn activates CEF. This activation could be from either H 2 O 2 acting as a redox signal, or by a secondary effect from H 2 O 2 inducing a deficit in ATP.

  10. A Content Analysis of Turkish Newspapers: Prevalence of Articles Containing Health Information Related to Physical Activity

    Science.gov (United States)

    Koksal, Leyla; Subasi, Feryal; Luleci, Emel; Hey, William

    2012-01-01

    This study was retrospective in design and the purpose was to review health information related to PA (physical activity) in articles of Turkish newspapers. The search covered newspaper articles printed between January 1, 2002 and December 31, 2004 in all Turkish newspapers that are accessible via the electronic newspaper database. Four daily…

  11. 78 FR 72688 - Information Collection Activities: Application for Permit To Drill; Proposed Collection; Comment...

    Science.gov (United States)

    2013-12-03

    ... determine the conditions of a drilling site to avoid hazards inherent in drilling operations. Specifically... drilling, sidetracking, or deepening operations. This includes the adequacy of the proposed casing design...; 134E1700D2 EEEE500000 ET1SF0000.DAQ000] Information Collection Activities: Application for Permit To Drill...

  12. 77 FR 16116 - Agency Information Collection; Activity Under OMB Review; Report of Extension of Credit to...

    Science.gov (United States)

    2012-03-19

    ... Information Collection; Activity Under OMB Review; Report of Extension of Credit to Political Candidates--Form... Approval No. 2138-0016. Title: Report of Extension of Credit to Political Candidates--Form 183 14 CFR Part 374a. Form No.: 183. Type of Review: Extension of a currently approved collection. Respondents...

  13. 75 FR 28859 - Agency Information Collection (Caution to Bidders-Bid Envelopes) Activities Under OMB Review

    Science.gov (United States)

    2010-05-24

    ... AFFAIRS Agency Information Collection (Caution to Bidders--Bid Envelopes) Activities Under OMB Review... burden; it includes the actual data collection instrument. DATES: Comments must be submitted on or before...) Provision 852.214-70, Caution to Bidders--Bid Envelopes. OMB Control Number: 2900-0593. Type of Review...

  14. 78 FR 42820 - Agency Information Collection (Caution to Bidders-Bid Envelopes) Activities Under OMB Review

    Science.gov (United States)

    2013-07-17

    ... AFFAIRS Agency Information Collection (Caution to Bidders--Bid Envelopes) Activities Under OMB Review... burden; it includes the actual data collection instrument. DATES: Comments must be submitted on or before... to Bidders--Bid Envelopes. OMB Control Number: 2900-0593. Type of Review: Revision of a currently...

  15. Generating passive NIR images from active LIDAR

    Science.gov (United States)

    Hagstrom, Shea; Broadwater, Joshua

    2016-05-01

    Many modern LIDAR platforms contain an integrated RGB camera for capturing contextual imagery. However, these RGB cameras do not collect a near-infrared (NIR) color channel, omitting information useful for many analytical purposes. This raises the question of whether LIDAR data, collected in the NIR, can be used as a substitute for an actual NIR image in this situation. Generating a LIDAR-based NIR image is potentially useful in situations where another source of NIR, such as satellite imagery, is not available. LIDAR is an active sensing system that operates very differently from a passive system, and thus requires additional processing and calibration to approximate the output of a passive instrument. We examine methods of approximating passive NIR images from LIDAR for real-world datasets, and assess differences with true NIR images.

  16. Transcriptome profiling of radish (Raphanus sativus L.) root and identification of genes involved in response to Lead (Pb) stress with next generation sequencing

    National Research Council Canada - National Science Library

    Wang, Yan; Xu, Liang; Chen, Yinglong; Shen, Hong; Gong, Yiqin; Limera, Cecilia; Liu, Liwang

    2013-01-01

    Lead (Pb), one of the most toxic heavy metals, can be absorbed and accumulated by plant roots and then enter the food chain resulting in potential health risks for human beings. The radish (Raphanus sativus L...

  17. Active maternal phenotype is established before breeding and leads offspring to align growth trajectory outcomes and reflex ontogeny.

    Science.gov (United States)

    Santana Muniz, Gisélia; Beserra, Renata; da Silva, Giselle de Paula; Fragoso, Jéssica; Lira, Allan de Oliveira; Nascimento, Elizabeth; Manhães de Castro, Raul; Leandro, Carol Góis

    2014-04-22

    The main goals of this study were to classify dams according to the level of voluntary physical activity before breeding and during pregnancy/lactation and to evaluate the effects on growth trajectory and reflex ontogenesis of offspring. Voluntary physical activity was ranked by traveled distance, time and daily estimated calorie burned. Thirty-five female Wistar rats were classified as control (C, n=5), inactive (I, n=10), active (A, n=8) and very active (VA, n=12). During 30d before breeding, traveled distance, average speed, time and calorie burned were daily recorded for active and very active groups. Traveled distance was recorded each 2h every day of adaptation. Body weight, food intake and fasting glycemia were measured throughout the experiment. During lactation, litters were evaluated in terms of physical features and reflex ontogeny. VA showed a progressive increase in the traveled distance and time while A dams presented constant values. VA rats showed lower body weight and higher food intake. During pregnancy, both groups performed less than 1km/day. Pups from A and VA dams showed higher lateral-lateral axis of the skull, longitudinal axis, tail length, and anticipation of the pavilion and auditory canal opening, and erupting incisors. I, A and VA groups showed a delay of righting, cliff aversion and vibrissae placing reflexes. In conclusion, active maternal phenotype is established before breeding allowing mothers to fit ecological and influencing growth trajectory outcomes and reflex ontogeny of the offspring based on matrilineal experience. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. "Life without nuclear power": A nuclear plant retirement formulation model and guide based on economics. San Onofre Nuclear Generating Station case: Economic impacts and reliability considerations leading to plant retirement

    Science.gov (United States)

    Wasko, Frank

    assessment review and then on to the stakeholder cost benefit analysis (if model qualifications are met) leading to a final plant retirement decision. This application via the model and guide, in turn, will lead electric utilities to explore system upgrade import opportunities and mitigation measures versus building new replacement generation facilities. United States nuclear reactors are licensed for 40 years with a 20 year extension available prior to the expiration date (EIA, 2013). Since late 2012, electric power companies have announced the early retirement of four uneconomical nuclear power plants while other studies have indicated that as many as 70 percent of United States nuclear power plants are potentially at risk for early retirement (Crooks, 2014 and Cooper, 2013). A high percentage of these aforementioned nuclear plants have operating licenses that will not expire until 2030 and beyond. Thus, for the most part, replacement power contingency planning has not been initiated for these plants or is still in preliminary stages. The recent nuclear plant retirements are the first since 1998 (EIA, 2013). Decisions to retire the plants involved concerns over maintenance and repair costs as well as declining profitability (EIA, 2013). In addition, the Energy Information Administration (2010-2012) released data that demonstrated that the worst 25 percent of United States nuclear plants are far more expensive to operate and generate electricity than new gas plants. It is equally important to understand and explain the economic and power replacement implications to both ratepayers and end-users. A SONGS case study analysis will review the economic, operational and political challenges that SCE faced leading to the retirement decision of SONGS. As preface to the case study, replacement steam generators (RSGs) were installed in Unit 2 in 2009 and in Unit 3 in 2010. In January 2012, while Unit 2 was down for routine maintenance, a small leak was discovered inside a steam

  19. Recovering lead from cupel waste generated in gold analysis by Pb-Fire assay.

    Science.gov (United States)

    Cerceau, Cristiane Isaac; Carvalho, Cornélio de Freitas; Rabelo, Ana Carolina Silveira; Dos Santos, Cláudio Gouvea; Gonçalves, Sabrina Mayra Dias; Varejão, Eduardo Vinícius Vieira

    2016-12-01

    Because of its precision and accuracy, Pb-Fire assay is the most employed method for gold analysis in geological materials. At the second stage of the method, namely cupellation, lead is oxidized to PbO which is absorbed by the cupel, leading to metallic gold as a tiny bend at the bottom of the recipient. After cupellation, cupel becomes highly contaminated with lead, making its disposal a serious risk of environmental contamination. In the present work, a leaching process for removing lead from cupel waste is proposed, which allowed for removing 96% of PbO by weight. After a precipitation step, 92.0% of lead was recovered from leachates in the form of PbSO4. Lead in the solid wastes left by the extraction was above the limit established by Brazilian legislation and these were classified as non-hazardous. Finally, secondary effluents generated after the precipitation step presented lead content more than twenty times lower than that of leachates from cupel waste. Tons of cupel waste are annually generated from gold analysis by Pb-Fire assay. Thus, the proposed method can contribute to prevent the discharge of high amounts of lead into the environment. Also, recovery of lead can help to partially meet the industrial demand for lead compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. From the field to classrooms: Scientists and educators collaborating to develop K-12 lessons on arctic carbon cycling and climate change that align with Next Generation Science Standards, and informal outreach programs that bring authentic data to informal audiences.

    Science.gov (United States)

    Brinker, R.; Cory, R. M.

    2014-12-01

    Next Generation Science Standards (NGSS) calls for students across grade levels to understand climate change and its impacts. To achieve this goal, the NSF-sponsored PolarTREC program paired an educator with scientists studying carbon cycling in the Arctic. The data collection and fieldwork performed by the team will form the basis of hands-on science learning in the classroom and will be incorporated into informal outreach sessions in the community. Over a 16-day period, the educator was stationed at Toolik Field Station in the High Arctic. (Toolik is run by the University of Alaska, Fairbanks, Institute of Arctic Biology.) She participated in a project that analyzed the effects of sunlight and microbial content on carbon production in Artic watersheds. Data collected will be used to introduce the following NGSS standards into the middle-school science curriculum: 1) Construct a scientific explanation based on evidence. 2) Develop a model to explain cycling of water. 3) Develop and use a model to describe phenomena. 4) Analyze and interpret data. 5) A change in one system causes and effect in other systems. Lessons can be telescoped to meet the needs of classrooms in higher or lower grades. Through these activities, students will learn strategies to model an aspect of carbon cycling, interpret authentic scientific data collected in the field, and conduct geoscience research on carbon cycling. Community outreach sessions are also an effective method to introduce and discuss the importance of geoscience education. Informal discussions of firsthand experience gained during fieldwork can help communicate to a lay audience the biological, physical, and chemical aspects of the arctic carbon cycle and the impacts of climate change on these features. Outreach methods will also include novel use of online tools to directly connect audiences with scientists in an effective and time-efficient manner.

  1. 77 FR 37696 - Notice of Proposed Information Collection: Survey and Collection of Information From HUD Lead...

    Science.gov (United States)

    2012-06-22

    ... Hazard Standards and the Lead-Based Paint Standard AGENCY: Office of Healthy Homes and Lead Hazard... techniques or other forms of information technology, e.g., permitting electronic submission of responses... the Lead Hazard Standards and the Lead-Based Paint Standard. OMB Control Number: Pending. Need for the...

  2. Natural products as leads to anticancer drugs.

    Science.gov (United States)

    Gordaliza, M

    2007-12-01

    Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as "lead" compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.

  3. Substrate Shuttling Between Active Sites of Uroporphyrinogen Decarboxylase in Not Required to Generate Coproporphyrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, J.; Warby, C; Whitby, F; Kushner, J; Hill, C

    2009-01-01

    Uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37), the fifth enzyme of the heme biosynthetic pathway, is required for the production of heme, vitamin B12, siroheme, and chlorophyll precursors. URO-D catalyzes the sequential decarboxylation of four acetate side chains in the pyrrole groups of uroporphyrinogen to produce coproporphyrinogen. URO-D is a stable homodimer, with the active-site clefts of the two subunits adjacent to each other. It has been hypothesized that the two catalytic centers interact functionally, perhaps by shuttling of reaction intermediates between subunits. We tested this hypothesis by construction of a single-chain protein (single-chain URO-D) in which the two subunits were connected by a flexible linker. The crystal structure of this protein was shown to be superimposable with wild-type activity and to have comparable catalytic activity. Mutations that impaired one or the other of the two active sites of single-chain URO-D resulted in approximately half of wild-type activity. The distributions of reaction intermediates were the same for mutant and wild-type sequences and were unaltered in a competition experiment using I and III isomer substrates. These observations indicate that communication between active sites is not required for enzyme function and suggest that the dimeric structure of URO-D is required to achieve conformational stability and to create a large active-site cleft.

  4. 78 FR 70931 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-11-27

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review and approval; Comment Request; William D. Ford Federal Direct Loan Program--150% Limitation AGENCY... Loan Program-- 150% Limitation OMB Control Number: 1845-0116 Type of Review: Extension without change...

  5. 78 FR 42951 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-18

    ... that promote healthy weight in LB women through a 16-week group support program, including physical... intervention will incorporate community-identified weight loss/risk reduction needs of this population... HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB for...

  6. 78 FR 78375 - Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers

    Science.gov (United States)

    2013-12-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers Correction In notice document 2013-30220 appearing on page 76851 of the issue...

  7. The Effect of Active Principles of Cilantro and Spirulina Powder on Lead Antagonism to Zinc and Iron in Carassius gibelio

    Directory of Open Access Journals (Sweden)

    Mărioara Nicula

    2017-05-01

    Cilantro and spirulina powder additionally administered in feed, has immobilized Pb through their active principles, thus decreasing its antagonistic effect expressed to Zn, even if Zn tissue level remained low. Pb antagonistic effect shown to Fe was diminished especially in tissue sampled from individuals receiving spirulina powder in feed.

  8. MHC class I signaling in T cells leads to tyrosine kinase activity and PLC-gamma 1 phosphorylation

    DEFF Research Database (Denmark)

    Skov, S; Odum, Niels; Claesson, M H

    1995-01-01

    phosphorylation and the subsequent calcium response. The early tyrosine kinase activity was found to be dependent on expression of the TCR/CD3 complex and the CD45 molecule on the surface of the T cells. Furthermore, MHC-I cross-linking was shown to tyrosine phosphorylate PLC-gamma 1 (phospholipase C-gamma 1...

  9. 77 FR 57105 - Notice of Proposed Information Collection: Collection of Information From HUD Lead Hazard Control...

    Science.gov (United States)

    2012-09-17

    ... or other forms of information technology, e.g., permitting electronic submission of responses. This... Affected Public: HUD Office of Healthy Homes and Lead Hazard Control's Lead-Based Paint Hazard Control...

  10. Research on Activators for Lead-Acid Batteries

    OpenAIRE

    Sugawara, Michio; Kozawa, Akiya

    2008-01-01

    Abstract : The ITE Battery Research group has developed a new organic battery activator for new and used lead-acid batteries. Ten years of investigation have established the validity of the ITE activator that prolongs the useful life of lead-acid batteries. It has been shown that the specific gravity of spent batteries can be restored to the original level in automotive, motive power; uninterruptible power supplies (UPS) and stationary energy storage batteries. Our results show that the disca...

  11. Novel nano-calcium phosphate generation to improve cell activity in bone restructuring

    CSIR Research Space (South Africa)

    Wepener, I

    2010-01-01

    Full Text Available : - Cell toxicity - Cell attachment - Cell cycle activation ? Unravelling signaling pathways and the relationship between osteoclasts and osteoblasts when responding to an implanted biomimetic bone scaffold, will provide improved understanding...

  12. Next Generation , Lightweight, Durable Boot Materials to Provide Active & Passive Thermal Protection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this NASA Phase I SBIR program is to leverage lightweight, durable materials developed by NanoSonic for use within extra vehicular activity (EVA)...

  13. Cognitive Orientation to (Daily) Occupational Performance intervention leads to improvements in impairments, activity and participation in children with Developmental Coordination Disorder.

    Science.gov (United States)

    Thornton, Ashleigh; Licari, Melissa; Reid, Siobhan; Armstrong, Jodie; Fallows, Rachael; Elliott, Catherine

    2016-01-01

    Children diagnosed with Developmental Coordination Disorder (DCD) present with a variety of impairments in fine and gross motor function, which impact on their activity and participation in a variety of settings. This research aimed to determine if a 10-week group-based Cognitive Orientation to Daily Occupational Performance (CO-OP) intervention improved outcome measures across the impairment, activity and participation levels of the International Classification of Functioning, Disability and Health (ICF) framework. In this quasi-experimental, pre-post-test, 20 male children aged 8-10 years (x9y1m ± 9 m) with a confirmed diagnosis of DCD participated in either the 10 week group intervention based on the CO-OP framework (n = 10) or in a control period of regular activity for 10 weeks (n = 10). Outcome measures relating to impairment (MABC-2, motor overflow assessment), activity (Handwriting Speed Test) and participation [Canadian Occupational Performance Measure, (COPM) and Goal Attainment Scale) were measured at weeks 0 and 10 in the intervention group. Children who participated in the CO-OP intervention displayed improvements in outcome measures for impairment, activity and participation, particularly a reduction in severity of motor overflow. Parent and child performance and satisfaction ratings on the COPM improved from baseline to week 10 and all goals were achieved at or above the expected outcome. No significant changes were reported for the control group in impairment and activity (participation was not measured for this group). The strategies implemented by children in the CO-OP treatment group, targeted towards individualised goal attainment, show that CO-OP, when run in a group environment, can lead to improvements across all levels of the ICF. Development Coordination Disorder is a condition which has significant physical, academic and social impacts on a child and can lead to activity limitations and participation restrictions. Cognitive

  14. Combinatorially Generated Piecewise Activation Functions

    OpenAIRE

    Chen, Justin

    2016-01-01

    In the neuroevolution literature, research has primarily focused on evolving the number of nodes, connections, and weights in artificial neural networks. Few attempts have been made to evolve activation functions. Research in evolving activation functions has mainly focused on evolving function parameters, and developing heterogeneous networks by selecting from a fixed pool of activation functions. This paper introduces a novel technique for evolving heterogeneous artificial neural networks t...

  15. Detection of induced mutations in CaFAD2 genes by next-generation sequencing leading to the production of improved oil composition in Crambe abyssinica.

    Science.gov (United States)

    Cheng, Jihua; Salentijn, Elma M J; Huang, Bangquan; Denneboom, Christel; Qi, Weicong; Dechesne, Annemarie C; Krens, Frans A; Visser, Richard G F; van Loo, Eibertus N

    2015-05-01

    Crambe abyssinica is a hexaploid oil crop for industrial applications. An increase of erucic acid (C22:1) and reduction of polyunsaturated fatty acid (PUFA) contents in crambe oil is a valuable improvement. An increase in oleic acid (C18:1), a reduction in PUFA and possibly an increase in C22:1 can be obtained by down-regulating the expression of fatty acid desaturase2 genes (CaFAD2), which code for the enzyme that converts C18:1 into C18:2. We conducted EMS-mutagenesis in crambe, followed by Illumina sequencing, to screen mutations in three expressed CaFAD2 genes. Two novel analysis strategies were used to detect mutation sites. In the first strategy, mutation detection targeted specific sequence motifs. In the second strategy, every nucleotide position in a CaFAD2 fragment was tested for the presence of mutations. Seventeen novel mutations were detected in 1100 one-dimensional pools (11 000 individuals) in three expressed CaFAD2 genes, including non-sense mutations and mis-sense mutations in CaFAD2-C1, -C2 and -C3. The homozygous non-sense mutants for CaFAD2-C3 resulted in a 25% higher content of C18:1 and 25% lower content of PUFA compared to the wild type. The mis-sense mutations only led to small changes in oil composition. Concluding, targeted mutation detection using NGS in a polyploid was successfully applied and it was found that a non-sense mutation in even a single CaFAD2 gene can lead to changes in crambe oil composition. Stacking the mutations in different CaFAD2 may gain additional changes in C18:1 and PUFA contents. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  16. Does Cardiac Rehabilitation After an Acute Cardiac Syndrome Lead to Changes in Physical Activity Habits? Systematic Review

    NARCIS (Netherlands)

    ter Hoeve, Nienke; Huisstede, Bionka M. A.; Stam, Henk J.; van Domburg, Ron T.; Sunamura, Madoka; van den Berg-Emons, Rita J. G.

    Background. Optimal physical activity levels have health benefits for patients with acute coronary syndrome (ACS) and are an important goal of cardiac rehabilitation (CR). Purpose. The purpose of this study was to systematically review literature regarding short-term effects (= 6 months after

  17. Can informed choice invitations lead to inequities in intentions to make lifestyle changes among participants in a primary care diabetes screening programme? Evidence from a randomized trial.

    Science.gov (United States)

    Kellar, I; Mann, E; Kinmonth, A L; Prevost, A T; Sutton, S; Marteau, T M

    2011-09-01

    To test whether information about benefits and harms of screening for type 2 diabetes increases intentions to make lifestyle changes amongst attenders, predominantly among the socially advantaged and those with a strong future time orientation. Planned subgroup analysis of attenders for screening participating in a randomized controlled trial of an informed choice invitation vs a standard invitation to attend for type 2 diabetes screening. Potentially eligible participants were identified from practice registers using routine data which were used to calculate risk scores for diabetes for all aged 40-69 years without known type 2 diabetes and area deprivation based on post code. In total, 1272 individuals in the top 25% risk category were randomized to receive one of two invitations to attend their practices for screening: an informed choice invitation or a standard invitation. The subsequent attenders completed self-report measures of future time orientation and deprivation immediately before undergoing a screening test. Individual-level deprivation demonstrated a significant moderator effect [F (4,635) = 4.32, P = 0.002]: individuals who were high in deprivation had lower intentions to engage in lifestyle change following receipt of the informed choice invitation. However, intentions were not patterned by deprivation when it was assessed at the area-level using the Index of Multiple Deprivation 2007. The hypothesized moderating effect of future time orientation on invitation type was also supported [F(14,613) = 2.46, P = 0.002): individuals low in future time orientation had markedly lower intentions to engage in lifestyle change following receipt of an informed choice invitation compared with a standard invitation for screening. Efforts to enhance informed choice where the implications of diagnosis are a requirement for lifestyle change may require that the immediate benefits are communicated, and efforts to address the apparent barriers to diabetes self

  18. Information literacy competency standards for higher education and their correlation with the cycle of knowledge generation

    Directory of Open Access Journals (Sweden)

    Alejandro Uribe Tirado

    2012-11-01

    Full Text Available This article considers the cycle of knowledge generation proposed by Nonaka and Takeuchi and sets out how the different indicators and expected results within the information literacy (IL standards used in higher education contribute to this cycle. After analyzing each standard and its interrelation with the four options to generate knowledge of Nonaka's cycle, it was identified that these standards are more geared to the generation of explicit knowledge, and therefore, it is necessary to work on other activities, and new proposed standards of IL that promote the generation of tacit knowledge and information processes needed.

  19. Enriching step-based product information models to support product life-cycle activities

    Science.gov (United States)

    Sarigecili, Mehmet Ilteris

    The representation and management of product information in its life-cycle requires standardized data exchange protocols. Standard for Exchange of Product Model Data (STEP) is such a standard that has been used widely by the industries. Even though STEP-based product models are well defined and syntactically correct, populating product data according to these models is not easy because they are too big and disorganized. Data exchange specifications (DEXs) and templates provide re-organized information models required in data exchange of specific activities for various businesses. DEXs show us it would be possible to organize STEP-based product models in order to support different engineering activities at various stages of product life-cycle. In this study, STEP-based models are enriched and organized to support two engineering activities: materials information declaration and tolerance analysis. Due to new environmental regulations, the substance and materials information in products have to be screened closely by manufacturing industries. This requires a fast, unambiguous and complete product information exchange between the members of a supply chain. Tolerance analysis activity, on the other hand, is used to verify the functional requirements of an assembly considering the worst case (i.e., maximum and minimum) conditions for the part/assembly dimensions. Another issue with STEP-based product models is that the semantics of product data are represented implicitly. Hence, it is difficult to interpret the semantics of data for different product life-cycle phases for various application domains. OntoSTEP, developed at NIST, provides semantically enriched product models in OWL. In this thesis, we would like to present how to interpret the GD & T specifications in STEP for tolerance analysis by utilizing OntoSTEP.

  20. E-Waste Informal Recycling: An Emerging Source of Lead Exposure in South America

    OpenAIRE

    Pascale, Antonio; Sosa, Adriana; Bares, Cristina; Battocletti, Alejandra; Moll, María José; Pose, Darío; Laborde, Amalia; González, Hugo; Feola, Gabriella

    2016-01-01

    BACKGROUND Primitive electronic waste (e-waste) recycling creates exposures to several hazardous substances including lead. In Uruguay, primitive recycling procedures are a significant source of lead exposure. OBJECTIVES The aim of this study was to examine lead exposure in blood lead levels (BLLs) in low-income children exposed to lead through burning cables. METHODS A sample of children and adolescents exposed to lead through burning cable activities were assessed at the Department of Toxic...

  1. Occipital alpha activity during stimulus processing gates the information flow to object-selective cortex.

    Directory of Open Access Journals (Sweden)

    Johanna M Zumer

    2014-10-01

    Full Text Available Given the limited processing capabilities of the sensory system, it is essential that attended information is gated to downstream areas, whereas unattended information is blocked. While it has been proposed that alpha band (8-13 Hz activity serves to route information to downstream regions by inhibiting neuronal processing in task-irrelevant regions, this hypothesis remains untested. Here we investigate how neuronal oscillations detected by electroencephalography in visual areas during working memory encoding serve to gate information reflected in the simultaneously recorded blood-oxygenation-level-dependent (BOLD signals recorded by functional magnetic resonance imaging in downstream ventral regions. We used a paradigm in which 16 participants were presented with faces and landscapes in the right and left hemifields; one hemifield was attended and the other unattended. We observed that decreased alpha power contralateral to the attended object predicted the BOLD signal representing the attended object in ventral object-selective regions. Furthermore, increased alpha power ipsilateral to the attended object predicted a decrease in the BOLD signal representing the unattended object. We also found that the BOLD signal in the dorsal attention network inversely correlated with visual alpha power. This is the first demonstration, to our knowledge, that oscillations in the alpha band are implicated in the gating of information from the visual cortex to the ventral stream, as reflected in the representationally specific BOLD signal. This link of sensory alpha to downstream activity provides a neurophysiological substrate for the mechanism of selective attention during stimulus processing, which not only boosts the attended information but also suppresses distraction. Although previous studies have shown a relation between the BOLD signal from the dorsal attention network and the alpha band at rest, we demonstrate such a relation during a visuospatial

  2. Influence of autocrine growth hormone on NF-κB activation leading to epithelial-mesenchymal transition of mammary carcinoma.

    Science.gov (United States)

    Baskari, Srinivas; Govatati, Suresh; Madhuri, Vijaya; Nallabelli, Nayudu; K, Paul Marx; Naik, Srinivas; Poornachandar; Balka, Swarna; Tamanam, Raghava Rao; Devi, Venkata Ramana

    2017-10-01

    Progression of breast cancers often depends on hormones among which human growth hormone is prominently involved in breast cancer progression. Earlier studies have reported constitutive activation of nuclear factor-κB, a key regulator of growth hormone receptor-mediated signaling pathway in breast carcinoma, but the precise molecular mechanisms are still elusive. In this study, we investigated the effect of human growth hormone on nuclear factor-κB activation and epithelial-mesenchymal transition in breast carcinoma. Our results explored that autocrine production of human growth hormone enhances cellular proliferation by the activation of nuclear factor-κB (65 kDa) and downregulation of E-cadherin expression. Furthermore, enhanced nuclear factor-κB expression significantly increases cell proliferation and diminishes apoptosis in MCF-7 cell line. Increased expression of nuclear factor-κB significantly enhances mammary carcinoma cell migration and invasion stimulated by autocrine human growth hormone, which results in epithelial-mesenchymal transition of MCF-7 cells. In conclusion, our study revealed the influence of human growth hormone on nuclear factor-κB activity and epithelial-mesenchymal transition in mammary carcinoma. Our findings will help to understand molecular role of "growth hormone-nuclear factor-κB axis" in mammary carcinogenesis which may facilitate the discovery of suitable pathway inhibitors for disease treatment.

  3. 78 FR 48439 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-08-08

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... Act of 1995, the Health Resources and Services Administration (HRSA) has submitted an Information... Child Health (MCH) Block Grant, administered by the Health Resources and Services Administration's...

  4. Transient Notch Activation Induces Long-Term Gene Expression Changes Leading to Sick Sinus Syndrome in Mice.

    Science.gov (United States)

    Qiao, Yun; Lipovsky, Catherine; Hicks, Stephanie; Bhatnagar, Somya; Li, Gang; Khandekar, Aditi; Guzy, Robert; Woo, Kel Vin; Nichols, Colin G; Efimov, Igor R; Rentschler, Stacey

    2017-08-18

    Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes. To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD]). Significant heart rate slowing and frequent sinus pauses are observed in iNICD mice when compared with controls. iNICD mice have structurally normal atria and preserved sinus node architecture, but expression of key transcriptional regulators of sinus node and atrial conduction, including Nkx2-5 (NK2 homeobox 5), Tbx3, and Tbx5 are dysregulated. To determine whether the induced electrical changes are stable, we transiently activated Notch followed by a prolonged washout period and observed that, in addition to decreased heart rate, atrial conduction velocity is persistently slower than control. Consistent with conduction slowing, genes encoding molecular determinants of atrial conduction velocity, including Scn5a (Nav1.5) and Gja5 (connexin 40), are persistently downregulated long after a transient Notch pulse. Consistent with the reduction in Scn5a transcript, Notch induces global changes in the atrial action potential, including a reduced dVm/dtmax. In addition, programmed electrical stimulation near the murine pulmonary vein demonstrates increased susceptibility to atrial arrhythmias in mice where Notch has been transiently activated. Taken together, these results suggest that transient Notch activation persistently alters ion channel gene expression and atrial electrophysiology and predisposes to an arrhythmogenic substrate. Our data provide evidence that Notch signaling regulates transcription factor and ion

  5. Blocking NF-κB nuclear translocation leads to p53-related autophagy activation and cell apoptosis

    Science.gov (United States)

    Zhu, Bao-Song; Xing, Chun-Gen; Lin, Fang; Fan, Xiao-Qing; Zhao, Kui; Qin, Zheng-Hong

    2011-01-01

    AIM: To investigate the anti-tumor effects of nuclear factor-κB (NF-κB) inhibitor SN50 and related mechanisms of SGC7901 human gastric carcinoma cells. METHODS: MTT assay was used to determine the cytotoxic effects of SN50 in gastric cancer cell line SGC7901. Hoechst 33258 staining was used to detect apoptosis morphological changes after SN50 treatment. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after SN50 treatment.Immunofluorescence staining was used to detect the expression of light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Western blotting analysis were used to determine the expression of proteins involved in apoptosis and autophagy including p53, p53 upregulated modulator of apoptosis (PUMA), damage-regulated autophagy modulator (DRAM), LC3 and Beclin 1. We detected the effects of p53-mediated autophagy activation on the apoptosis of SGC7901 cells with the p53 inhibitor pifithrin-α. RESULTS: The viability of SGC7901 cells was inhibited after SN50 treatment. Inductions in the expression of apoptotic protein p53 and PUMA as well as autophagic protein DRAM, LC3 and Beclin 1 were detected with Western blotting analysis. SN50-treated cells exhibited punctuate microtubule-associated protein 1 LC3 in immunoreactivity and MDC-labeled vesicles increased after treatment of SN50 by MDC staining. Collapse of mitochondrial membrane potential Δψ were detected for 6 to 24 h after SN50 treatment. SN50-induced increases in PUMA, DRAM, LC3 and Beclin 1 and cell death were blocked by the p53 specific inhibitor pifithrin-α. CONCLUSION: The anti-tumor activity of NF-κB inhibitors is associated with p53-mediated activation of autophagy. PMID:21274377

  6. Ameloblasts require active RhoA to generate normal dental enamel.

    Science.gov (United States)

    Xue, Hui; Li, Yong; Everett, Eric T; Ryan, Kathleen; Peng, Li; Porecha, Rakhee; Yan, Yan; Lucchese, Anna M; Kuehl, Melissa A; Pugach, Megan K; Bouchard, Jessica; Gibson, Carolyn W

    2013-08-01

    RhoA plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment, and cell proliferation. During amelogenesis, ameloblasts (which produce the enamel proteins) undergo dramatic cytoskeletal changes and the RhoA protein level is up-regulated. Transgenic mice were generated that express a dominant-negative RhoA transgene in ameloblasts using amelogenin gene-regulatory sequences. Transgenic and wild-type (WT) molar tooth germs were incubated with sodium fluoride (NaF) or sodium chloride (NaCl) in organ culture. Filamentous actin (F-actin) stained with phalloidin was elevated significantly in WT ameloblasts treated with NaF compared with WT ameloblasts treated with NaCl or with transgenic ameloblasts treated with NaF, thereby confirming a block in the RhoA/Rho-associated protein kinase (ROCK) pathway in the transgenic mice. Little difference in quantitative fluorescence (an estimation of fluorosis) was observed between WT and transgenic incisors from mice provided with drinking water containing NaF. We subsequently found reduced transgene expression in incisors compared with molars. Transgenic molar teeth had reduced amelogenin, E-cadherin, and Ki67 compared with WT molar teeth. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein, amelogenin, and E-cadherin and cell proliferation are regulated by RhoA in other tissues. Together these findings reveal deficits in molar ameloblast function when RhoA activity is inhibited. © 2013 Eur J Oral Sci.

  7. 77 FR 32593 - Agency Information Collection Activities; Notice of Intent To Renew Collection: Rules Relating To...

    Science.gov (United States)

    2012-06-01

    ... Delivery/Courier: Same as mail above. Federal eRulemaking Portal: http://www.regulations.gov . Follow the... information, and to allow 60 days for public comment in response to the notice. This notice solicits comments... provide a 60-day notice in the Federal Register concerning each proposed collection of information...

  8. 6 Ways Hotel Marketing Can Generate More Leads for the Sales Team

    OpenAIRE

    2017-01-01

    Achieving group and meetings revenue targets can make or break your property’s annual performance. But incredibly, most hotel group sales departments lack consistent, effective marketing support and are forced to generate their own leads. Hotel marketers often ignore the need to boost their hotel’s revenue by accelerating the number of incoming sales leads. As a result, hotel marketing departments usually stick to what they know: marketing only to leisure travelers. Let’s change that

  9. Sentinel-1 data exploitation for geohazard activity map generation

    Science.gov (United States)

    Barra, Anna; Solari, Lorenzo; Béjar-Pizarro, Marta; Monserrat, Oriol; Herrera, Gerardo; Bianchini, Silvia; Crosetto, Michele; María Mateos, Rosa; Sarro, Roberto; Moretti, Sandro

    2017-04-01

    This work is focused on geohazard mapping and monitoring by exploiting Sentinel-1 (A and B) data and the DInSAR (Differential interferometric SAR (Synthetic Aperture Radar)) techniques. Sometimes the interpretation of the DInSAR derived product (like the velocity map) can be complex, mostly for a final user who do not usually works with radar. The aim of this work is to generate, in a rapid way, a clear product to be easily exploited by the authorities in the geohazard management: intervention planning and prevention activities. Specifically, the presented methodology has been developed in the framework of the European project SAFETY, which is aimed at providing Civil Protection Authorities (CPA) with the capability of periodically evaluating and assessing the potential impact of geohazards (volcanic activity, earthquakes, landslides and subsidence) on urban areas. The methodology has three phases, the interferograms generation, the activity map generation, in terms of velocity and accumulated deformation (with time-series), and the Active Deformation Area (ADA) map generation. The last one is the final product, derived from the original activity map by analyzing the data in a Geographic Information System (GIS) environment, which isolate only the true deformation areas over the noise. This product can be more easily read by the authorities than the original activity map, i.e. can be better exploited to integrate other information and analysis. This product also permit an easy monitoring of the active areas.

  10. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R

    1993-01-01

    the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...... is required for stable interaction with pRB in vivo and that trans-activation by E2F-1/DP-1 heterodimers is inhibited by pRB. We suggest that "E2F" is the activity that is formed when an E2F-1-related protein and a DP-1-related protein dimerize.......The E2F transcription factor has been implicated in the regulation of genes whose products are involved in cell proliferation. Two proteins have recently been identified with E2F-like properties. One of these proteins, E2F-1, has been shown to mediate E2F-dependent trans-activation and to bind...

  11. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI.

    Science.gov (United States)

    Kegel, Victoria; Pfeiffer, Elisa; Burkhardt, Britta; Liu, Jia L; Zeilinger, Katrin; Nüssler, Andreas K; Seehofer, Daniel; Damm, Georg

    2015-01-01

    Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 10(6) cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  12. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Directory of Open Access Journals (Sweden)

    Victoria Kegel

    2015-01-01

    Full Text Available Drug induced liver injury (DILI is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2±0.9×106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay and cell activity (XTT assay. The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  13. Cued Reactivation of Motor Learning during Sleep Leads to Overnight Changes in Functional Brain Activity and Connectivity.

    Directory of Open Access Journals (Sweden)

    James N Cousins

    2016-05-01

    Full Text Available Sleep plays a role in memory consolidation. This is demonstrated by improved performance and neural plasticity underlying that improvement after sleep. Targeted memory reactivation (TMR allows the manipulation of sleep-dependent consolidation through intentionally biasing the replay of specific memories in sleep, but the underlying neural basis of these altered memories remains unclear. We use functional magnetic resonance imaging (fMRI to show a change in the neural representation of a motor memory after targeted reactivation in slow-wave sleep (SWS. Participants learned two serial reaction time task (SRTT sequences associated with different auditory tones (high or low pitch. During subsequent SWS, one sequence was reactivated by replaying the associated tones. Participants were retested on both sequences the following day during fMRI. As predicted, they showed faster reaction times for the cued sequence after targeted memory reactivation. Furthermore, increased activity in bilateral caudate nucleus and hippocampus for the cued relative to uncued sequence was associated with time in SWS, while increased cerebellar and cortical motor activity was related to time in rapid eye movement (REM sleep. Functional connectivity between the caudate nucleus and hippocampus was also increased after targeted memory reactivation. These findings suggest that the offline performance gains associated with memory reactivation are supported by altered functional activity in key cognitive and motor networks, and that this consolidation is differentially mediated by both REM sleep and SWS.

  14. Cued Reactivation of Motor Learning during Sleep Leads to Overnight Changes in Functional Brain Activity and Connectivity.

    Science.gov (United States)

    Cousins, James N; El-Deredy, Wael; Parkes, Laura M; Hennies, Nora; Lewis, Penelope A

    2016-05-01

    Sleep plays a role in memory consolidation. This is demonstrated by improved performance and neural plasticity underlying that improvement after sleep. Targeted memory reactivation (TMR) allows the manipulation of sleep-dependent consolidation through intentionally biasing the replay of specific memories in sleep, but the underlying neural basis of these altered memories remains unclear. We use functional magnetic resonance imaging (fMRI) to show a change in the neural representation of a motor memory after targeted reactivation in slow-wave sleep (SWS). Participants learned two serial reaction time task (SRTT) sequences associated with different auditory tones (high or low pitch). During subsequent SWS, one sequence was reactivated by replaying the associated tones. Participants were retested on both sequences the following day during fMRI. As predicted, they showed faster reaction times for the cued sequence after targeted memory reactivation. Furthermore, increased activity in bilateral caudate nucleus and hippocampus for the cued relative to uncued sequence was associated with time in SWS, while increased cerebellar and cortical motor activity was related to time in rapid eye movement (REM) sleep. Functional connectivity between the caudate nucleus and hippocampus was also increased after targeted memory reactivation. These findings suggest that the offline performance gains associated with memory reactivation are supported by altered functional activity in key cognitive and motor networks, and that this consolidation is differentially mediated by both REM sleep and SWS.

  15. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I

    Energy Technology Data Exchange (ETDEWEB)

    Strand, Deserah D.; Livingston, Aaron K.; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M.; Fisher, Nicholas; Froehlich, John E.; Cruz, Jeffrey A.; Minhas, Deepika; Hixson, Kim K.; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M.

    2017-01-13

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (hcef2) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force (pmf), activation of the photoprotective qE response, and the accumulation of H2O2 . Surprisingly, hcef2 was mapped to a nonsense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash induced thylakoid electric field suggest that these defect lead to accumulation of H2O2 in hcef2, which we have previously shown leads to activation of NDHrelated CEF. We observed similar increases in CEF and H2O2 accumulation in other translation defective mutants, suggesting that loss of coordination in plastid protein levels lead to imbalances in the photosynthetic energy balance that leads to increased CEF. These results, together with a large body of previous observations, support a general model in which processes that imbalances in chloroplast energetics result in the production of H2O2 , which activates CEF, either as a redox signal or by inducing deficits in ATP levels.

  16. Collaboration leads to enhanced curriculum.

    Science.gov (United States)

    Valerius, J; Mohan, V; Doctor, D; Hersh, W

    2015-01-01

    In 2007, we initiated a health information management (HIM) track of our biomedical informatics graduate program, and subsequent ongoing program assessment revealed a confluence of topics and courses within HIM and clinical informatics (CI) tracks. We completed a thorough comparative analysis of competencies derived from AMIA, AHIMA, and CAHIIM. Coupled with the need to streamline course offerings, the process, described in this paper allowed new opportunities for faculty collaboration, resulted in the creation of a model assessment for best practice in courses, and led to new avenues of growth within the program. The objective of the case study is to provide others in the informatics educational community with a model for analysis of curriculum in order to improve quality of student learning. We describe a case study where an academic informatics program realigned its course offerings to better reflect the HIM of today, and prepare for challenges of the future. Visionary leadership, intra-departmental self-analysis and alignment of the curriculum through defined mapping process reduced overlap within the CI and HIM tracks. Teaching within courses was optimized through the work of core faculty collaboration. The analysis of curriculum resulted in reduction of overlap within course curriculum. This allowed for additional and new course content to be added to existing courses. Leadership fostered an environment where top-down as well as bottom-up collaborative assessment activities resulted in a model to consolidate learning and reduce unnecessary duplication within courses. A focus on curriculum integration, emphasis on course alignment and strategic consolidation of course content raised the quality of informatics education provided to students. Faculty synergy was an essential component of this redesign process. Continuous quality improvement strategy included an ongoing alignment of curriculum and competencies through a comparative analysis approach. Through

  17. Cross-presentation of viral antigens in dribbles leads to efficient activation of virus-specific human memory T cells.

    Science.gov (United States)

    Ye, Wei; Xing, Yun; Paustian, Christopher; van de Ven, Rieneke; Moudgil, Tarsem; Hilton, Traci L; Fox, Bernard A; Urba, Walter J; Zhao, Wei; Hu, Hong-Ming

    2014-04-16

    Autophagy regulates innate and adaptive immune responses to pathogens and tumors. We have reported that autophagosomes derived from tumor cells after proteasome inhibition, DRibbles (Defective ribosomal products in blebs), were excellent sources of antigens for efficient cross priming of tumor-specific CD8⁺ T cells, which mediated regression of established tumors in mice. But the activity of DRibbles in human has not been reported. DRibbles or cell lysates derived from HEK293T or UbiLT3 cell lines expressing cytomegalovirus (CMV) pp65 protein or transfected with a plasmid encoding dominant HLA-A2 restricted CMV, Epstein-Barr virus (EBV), and Influenza (Flu) epitopes (CEF) were loaded onto human monocytes or PBMCs and the response of human CMV pp65 or CEF antigen-specific CD4⁺ and CD8⁺ memory T cells was detected by intracellular staining. The effect of cytokines (GM-CSF, IL-4, IL-12, TNF-α, IFN-α and IFN-γ) TLR agonists (Lipopolysaccharide, Polyinosinic-polycytidylic acid (poly(I:C), M52-CpG, R848, TLR2 ligand) and CD40 ligand on the cross-presentation of antigens contained in DRibbles or cell lysates was explored. In this study we showed that purified monocytes, or human PBMCs, loaded with DRibbles isolated from cells expressing CMV or CEF epitopes, could activate CMV- or CEF-specific memory T cells. DRibbles were significantly more efficient at stimulating CD8⁺ memory T cells compared to cell lysates expressing the same antigenic epitopes. We optimized the conditions for T-cell activation and IFN-γ production following direct loading of DRibbles onto PBMCs. We found that the addition of Poly(I:C), CD40 ligand, and GM-CSF to the PBMCs together with DRibbles significantly increased the level of CD8⁺ T cell responses. DRibbles containing specific viral antigens are an efficient ex vivo activator of human antigen-specific memory T cells specific for those antigens. This function could be enhanced by combining with Poly(I:C), CD40 ligand, and GM

  18. Reduction of Ether-Type Glycerophospholipids, Plasmalogens, by NF-κB Signal Leading to Microglial Activation.

    Science.gov (United States)

    Hossain, Md Shamim; Abe, Yuichi; Ali, Fatma; Youssef, Mohammed; Honsho, Masanori; Fujiki, Yukio; Katafuchi, Toshihiko

    2017-04-12

    Neuroinflammation characterized by activation of glial cells is observed in various neurodegenerative diseases including Alzheimer's disease (AD). Although the reduction of ether-type glycerophospholipids, plasmalogens (Pls), in the brain is reported in AD patients, the mechanism of the reduction and its impact on neuroinflammation remained elusive. In the present study, we found for the first time that various inflammatory stimuli reduced Pls levels in murine glial cells via NF-κB activation, which then downregulated a Pls-synthesizing enzyme, glycerone phosphate O-acyltransferase (Gnpat) through increased c-Myc recruitment onto the Gnpat promoter. We also found that systemic injection of lipopolysaccharide, aging, and chronic restraint stress reduced brain Pls contents that were associated with glial NF-κB activation, an increase in c-Myc expression, and downregulation of Gnpat in the mouse cortex and hippocampus. More interestingly, the reduction of Pls contents in the murine cortex itself could increase the activated phenotype of microglial cells and the expression of proinflammatory cytokines, suggesting further acceleration of neuroinflammation by reduction of brain Pls. A similar mechanism of Gnpat reduction was also found in human cell lines, triple-transgenic AD mouse brain, and postmortem human AD brain tissues. These findings suggest a novel mechanism of neuroinflammation that may explain prolonged progression of AD and help us to explore preventive and therapeutic strategies to treat neurodegenerative diseases.SIGNIFICANCE STATEMENT Ether-type glycerophospholipids, plasmalogens (Pls), are reduced in the brain of Alzheimer disease (AD) patients. We found that inflammatory stimuli reduced Pls contents by downregulation of the Pls-synthesizing enzyme glycerone phosphate O-acyltransferase (Gnpat) through NF-κB-mediated recruitment of c-Myc onto the Gnpat promoter in both murine and human cell lines. Murine brains after systemic lipopolysaccharide

  19. From drug target to leads--sketching a physicochemical pathway for lead molecule design in silico.

    Science.gov (United States)

    Shaikh, S A; Jain, T; Sandhu, G; Latha, N; Jayaram, B

    2007-01-01

    The discovery of new pharmaceuticals via computer modeling is one of the key challenges in modern medicine. The advent of global networks of genomic, proteomic and metabolomic endeavors is ushering in an increasing number of novel and clinically important targets for screening. Computational methods are anticipated to play a pivotal role in exploiting the structural and functional information to understand specific molecular recognition events of the target macromolecule with candidate hits leading ultimately to the design of improved leads for the target. In this review, we sketch a system independent, comprehensive physicochemical pathway for lead molecule design focusing on the emerging in silico trends and techniques. We survey strategies for the generation of candidate molecules, docking them with the target and ranking them based on binding affinities. We present a molecular level treatment for distinguishing affinity from specificity of a ligand for a given target. We also discuss the significant aspects of drug absorption, distribution, metabolism, excretion and toxicity (ADMET) and highlight improved protocols required for higher quality and throughput of in silico methods employed at early stages of discovery. We present a realization of the various stages in the pathway proposed with select examples from the literature and from our own research to demonstrate the way in which an iterative process of computer design and validation can aid in developing potent leads. The review thus summarizes recent advances and presents a viewpoint on improvements envisioned in the years to come for automated computer aided lead molecule discovery.

  20. A lead-free flexible structure for piezoelectric power generation

    Science.gov (United States)

    Kho, Byung Woo; Yun, Byung Kil; Jung, Jong Hoon; Lee, Minbaek

    2014-06-01

    Here, we demonstrate a fully-flexible piezoelectric hybrid structure composed of sodium niobate nanocubes and polyvinylidene fluoride. Hydrothermally-grown sodium niobate nanocubes show an orthorhombic crystal structure with Pmc21 symmetry, and polyvinylidene fluoride is electrically poled for the β-phase, each of those represents piezoelectricity. Hybrid devices were electrically tested in two different modes by applying forces parallel to the in-plane and the out-of-plane directions of the piezoelectric layer. Our device shows an output voltage, current, and power density of 2.9 V, 68 nA, and 4.4 μWcm-3, respectively, at a pushing force of 5 kgf and a frequency of 1 Hz. The output power generation also shows a linear relation with the applied force over a wide range of 1-5 kgf. This implies our flexible hybrid piezoelectric structure can be adapted to various mechanical environments. Our unique structure should open up various application areas of piezoelectric materials such as touch sensors, flexible energy harvesters and eco-friendly piezoelectric actuators.

  1. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  2. Taking the Lead : Gender, Social Context and Preference to Lead

    NARCIS (Netherlands)

    Hong, A.P.C.I.; Schaafsma, J.; van der Wijst, P.J.

    Previous research has demonstrated that women tend to emerge as leaders less often than men. In the present study, we examined to what extent women's and men's preference to lead is influenced by social context. It was hypothesized that women have a less strong preference to lead than men in a

  3. Using visual information analysis to explore complex patterns in the activity of designers

    DEFF Research Database (Denmark)

    Cash, Philip; Stanković, Tino; Štorga, Mario

    2014-01-01

    the temporality of interrelations between interlinked variables and, as such, can be applied to a range of datasets. By providing a statistical analysis of the networks’ growth the proposed method allows for the modelling of complex patterns of activity. Throughout, the method is demonstrated with respect......The analysis of complex interlinked datasets poses a significant problem for design researchers. This is addressed by proposing an information visualisation method for analysing patterns of design activity, qualitatively and quantitatively, with respect to time. This method visualises...

  4. Chronic lung injury by constitutive expression of activation-induced cytidine deaminase leads to focal mucous cell metaplasia and cancer.

    Science.gov (United States)

    Kitamura, Jiro; Uemura, Munehiro; Kurozumi, Mafumi; Sonobe, Makoto; Manabe, Toshiaki; Hiai, Hiroshi; Date, Hiroshi; Kinoshita, Kazuo

    2015-01-01

    Activation-induced cytidine deaminase (AID) is an enzyme required for antibody diversification, and it causes DNA mutations and strand breaks. Constitutive AID expression in mice invariably caused lung lesions morphologically similar to human atypical adenomatous hyperplasia (AAH), which can be a precursor of bronchioloalveolar carcinoma. Similar to AAH, mouse AAH-like lesion (MALL) exhibited signs of alveolar differentiation, judging from the expression of alveolar type II (AT2) cell marker surfactant protein C (SP-C). However, electron microscopy indicated that MALL, which possessed certain features of a mucous cell, is distinct from an AAH or AT2 cell. Although MALL developed in all individuals within 30 weeks after birth, lung tumors occurred in only 10%; this suggests that the vast majority of MALLs fail to grow into visible tumors. MALL expressed several recently described markers of lung alveolar regeneration such as p63, keratin 5, keratin 14, leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), and Lgr6. Increased cell death was observed in the lungs of AID transgenic mice compared with wild-type mice. Based on these observations, we speculate that MALL is a regenerating tissue compensating for cellular loss caused by AID cytotoxicity. AID expression in such regenerating tissue should predispose cells to malignant transformation via its mutagenic activity.

  5. Inhibition of carnitine palmitoyltransferase leads to induction of 3-hydroxymethylglutaryl coenzyme A reductase activity in rat liver

    NARCIS (Netherlands)

    H. Jansen (Hans); N. Hoogerbrugge van der Linden (N.); W.C. Hülsmann (William)

    1990-01-01

    markdownabstractAbstract The relation between carnitine palmitoyltransferase (CPT) activity and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity was investigated. Rats were treated with aminocarnitine or 1-carnitine overnight. In rats, in which CPT activity was inhibited by

  6. Ambient Information Systems to Support the Elderly in Carrying Out Their Activities of Daily Living

    Science.gov (United States)

    García-Vázquez, Juan Pablo; Rodríguez, Marcela D.

    As they age, older adult's present losses in their functional capabilities which cause them can't continue performing their activities of daily living (ADL) independently at home. We propose Ambient Information Systems (AIS) as appropriate pervasive devices to promote their independent living. Therefore our aim is to determine the utility and usability of AIS to support the independent life of older adults by helping them to perform their activities. In this paper we present preliminary results of a case study that we carried out for understanding the problems and needs that older adults face in doing some of their activities of daily living. In particular, we present results regarding the elderly problems to adhere to their medication prescription. Based on these results we propose AIS to support older adults to medicate. Finally, we present the design attributes incorporated into this AIS, which were identified from the design taxonomies of AIS reported in the literature.

  7. Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling

    2015-12-01

    Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.

  8. Activation of SO2 and CO2 by trivalent uranium leading to sulfite/dithionite and carbonate/oxalate complexes.

    Science.gov (United States)

    Schmidt, Anna-Corina; Heinemann, Frank W; Kefalidis, Christos E; Maron, Laurent; Roesky, Peter W; Meyer, Karsten

    2014-10-13

    The first sulfite [{(((nP,Me) ArO)3 tacn)U(IV) }2 (μ-κ(1) :κ(2) -SO3 )] (tacn=triazacyclononane) and dithionite [{(((nP,Me) ArO)3 tacn)U(IV) }2 (μ-κ(2) :κ(2) -S2 O4 )] complexes of uranium from reaction with gaseous SO2 have been prepared. Additionally, the reductive activation of CO2 was investigated with respect to the rare oxalate [{(((nP,Me) ArO)3 tacn)U(IV) }2 (μ-κ(2) :κ(2) -C2 O4 )] formation. This ultimately provides the unique S2 O4 (2-) /C2 O4 (2-) and SO3 (2-) /CO3 (2-) complex pairs. All new complexes were characterized by a combination of single-crystal X-ray diffraction, elemental analysis, UV/Vis/NIR electronic absorption, IR vibrational, and (1) H NMR spectroscopy, as well as magnetization (VT SQUID) studies. Moreover, density functional theory (DFT) calculations were carried out to gain further insight into the reaction mechanisms. All observations, together with DFT, support the assumption that SO2 and CO2 show similar (dithionite/oxalate) to analogous (sulfite/carbonate) activation behavior with uranium complexes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception.

    Science.gov (United States)

    Bang, S; Yoo, S; Yang, T J; Cho, H; Kim, Y G; Hwang, S W

    2010-10-01

    Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in primary sensory neurons and skin keratinocytes play a crucial role as peripheral pain detectors. Many natural and synthetic ligands have been found to act on thermoTRPs, but little is known about endogenous compounds that inhibit these TRPs. Here, we asked whether resolvin D1 (RvD1), a naturally occurring anti-inflammatory and pro-resolving lipid molecule is able to affect the TRP channel activation. We examined the effect of RvD1 on the six thermoTRPs using Ca(2+) imaging and whole cell electrophysiology experiments using the HEK cell heterologous expression system, cultured sensory neurons and HaCaT keratinocytes. We also checked changes in agonist-specific acute licking/flicking or flinching behaviours and TRP-related mechanical and thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay systems with or without inflammation. RvD1 inhibited the activities of TRPA1, TRPV3 and TRPV4 at nanomolar and micromolar levels. Consistent attenuations in agonist-specific acute pain behaviours by immediate peripheral administration with RvD1 were also observed. Furthermore, local pretreatment with RvD1 significantly reversed mechanical and thermal hypersensitivity in inflamed tissues. RvD1 was a novel endogenous inhibitor for several sensory TRPs. The results of our behavioural studies suggest that RvD1 has an analgesic potential via these TRP-related mechanisms.

  10. Options to Improve the Quality of Wind Generation Output Forecasting with the Use of Available Information as Explanatory Variables

    Directory of Open Access Journals (Sweden)

    Rafał Magulski

    2015-06-01

    Full Text Available Development of wind generation, besides its positive aspects related to the use of renewable energy, is a challenge from the point of view of power systems’ operational security and economy. The uncertain and variable nature of wind generation sources entails the need for the for the TSO to provide adequate reserves of power, necessary to maintain the grid’s stable operation, and the actors involved in the trading of energy from these sources incur additional of balancing unplanned output deviations. The paper presents the results of analyses concerning the options to forecast a selected wind farm’s output exercised by means of different methods of prediction, using a different range of measurement and forecasting data available on the farm and its surroundings. The analyses focused on the evaluation of forecast errors, and selection of input data for forecasting models and assessment of their impact on prediction quality improvement.

  11. Online visual feedback during error-free channel trials leads to active unlearning of movement dynamics: evidence for adaptation to trajectory prediction errors.

    Directory of Open Access Journals (Sweden)

    Angel Lago-Rodriguez

    2016-09-01

    Full Text Available Prolonged exposure to movement perturbations leads to creation of motor memories which decay towards previous states when the perturbations are removed. However, it remains unclear whether this decay is due only to a spontaneous and passive recovery of the previous state. It has recently been reported that activation of reinforcement-based learning mechanisms delays the onset of the decay. This raises the question whether other motor learning mechanisms may also contribute to the retention and/or decay of the motor memory. Therefore, we aimed to test whether mechanisms of error-based motor adaptation are active during the decay of the motor memory. Forty-five right-handed participants performed point-to-point reaching movements under an external dynamic perturbation. We measured the expression of the motor memory through error-clamped (EC trials, in which lateral forces constrained movements to a straight line towards the target. We found greater and faster decay of the motor memory for participants who had access to full online visual feedback during these EC trials (Cursor group, when compared with participants who had no EC feedback regarding movement trajectory (Arc group. Importantly, we did not find between-group differences in adaptation to the external perturbation. In addition, we found greater decay of the motor memory when we artificially increased feedback errors through the manipulation of visual feedback (Augmented-Error group. Our results then support the notion of an active decay of the motor memory, suggesting that adaptive mechanisms are involved in correcting for the mismatch between predicted movement trajectories and actual sensory feedback, which leads to greater and faster decay of the motor memory.

  12. Access to hands-on mathematics measurement activities using robots controlled via speech generating devices: three case studies.

    Science.gov (United States)

    Adams, Kim; Cook, Al

    2014-07-01

    To examine how using a robot controlled via a speech generating device (SGD) influences the ways students with physical and communication limitations can demonstrate their knowledge in math measurement activities. Three children with severe physical disabilities and complex communication needs used the robot and SGD system to perform four math measurement lessons in comparing, sorting and ordering objects. The performance of the participants was measured and the process of using the system was described in terms of manipulation and communication events. Stakeholder opinions were solicited regarding robot use. Robot use revealed some gaps in the procedural knowledge of the participants. Access to both the robot and SGD was shown to provide several benefits. Stakeholders thought the intervention was important and feasible for a classroom environment. The participants were able to participate actively in the hands-on and communicative measurement activities and thus meet the demands of current math instruction methods. Current mathematics pedagogy encourages doing hands-on activities while communicating about concepts. Adapted Lego robots enabled children with severe physical disabilities to perform hands-on length measurement activities. Controlling the robots from speech generating devices (SGD) enabled the children, who also had complex communication needs, to reflect and report on results during the activities. By using the robots combined with SGDs, children both exhibited their knowledge of and experienced the concepts of mathematical measurements.

  13. How to lead complex situations

    DEFF Research Database (Denmark)

    Hansen, Michael Pingel

    2013-01-01

    The military leader is experiencing increasingly more complex situations, whether it is as leader in a foreign combat environment or in the home-based public administration. Complex situations like these call for a special set of managerial responses and a special way of leading organisations....... The proposition of this article is that the methods that drive innovative processes, strengthening the creative culture, are necessary to manage complex situations in military contexts....

  14. Treatment of Nuclear Data Covariance Information in Sample Generation

    Energy Technology Data Exchange (ETDEWEB)

    Swiler, Laura Painton [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Adams, Brian M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wieselquist, William [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division

    2017-10-01

    This report summarizes a NEAMS (Nuclear Energy Advanced Modeling and Simulation) project focused on developing a sampling capability that can handle the challenges of generating samples from nuclear cross-section data. The covariance information between energy groups tends to be very ill-conditioned and thus poses a problem using traditional methods for generated correlated samples. This report outlines a method that addresses the sample generation from cross-section matrices.

  15. 75 FR 30812 - Agency Information Collection Activities: Request for Comments on Thirty-One Proposed Information...

    Science.gov (United States)

    2010-06-02

    ... consolidated at 40 CFR part 9. B. What information collection activity or ICR does this apply to? In compliance... Polyurethane Foam Production and Fabrication, Lead Acid Battery Manufacturing, and Wood Preserving. ] ICR...: Chromium Compounds, Flexible Polyurethane Foam Production and Fabrication, Lead Acid Battery Manufacturing...

  16. Cidal activity of oral third-generation cephalosporins against Streptococcus pneumoniae in relation to cefotaxime intrinsic activity.

    Science.gov (United States)

    Cafini, F; Aguilar, L; Alou, L; Giménez, M J; Sevillano, D; Torrico, M; González, N; Granizo, J J; Martín-Herrero, J E; Prieto, J

    2008-08-01

    This study explores the killing kinetics within 12 h of four oral third-generation cephalosporins against ten Streptococcus pneumoniae strains exhibiting cefotaxime minimum inhibitory concentrations (MICs) from 0.03 to 2 microg/ml. Killing curves were performed with concentrations achievable in serum after standard doses (0.015-4 microg/ml). Reductions of 90% were achieved with all compounds at serum-achievable concentrations for strains exhibiting cefotaxime MIC or = 1 microg/ml, only cefditoren reached a 90% reduction with concentrations of 0.5-1 microg/ml doses. At 4 microg/ml, cefditoren and cefotaxime reached 99.9% reduction in seven of the ten strains studied. At serum-achievable concentrations, cefdinir and cefixime were not bactericidal against strains exhibiting cefotaxime MIC > or = 0.25 microg/ml and > or = 0.5 microg/ml, respectively. Cefditoren showed the best killing kinetic profiles and this observation may be important when choosing an oral third-generation cephalosporin as initial or sequential therapy.

  17. More target features in visual working memory leads to poorer search guidance: Evidence from contralateral delay activity

    Science.gov (United States)

    Schmidt, Joseph; MacNamara, Annmarie; Proudfit, Greg Hajcak; Zelinsky, Gregory J.

    2014-01-01

    The visual-search literature has assumed that the top-down target representation used to guide search resides in visual working memory (VWM). We directly tested this assumption using contralateral delay activity (CDA) to estimate the VWM load imposed by the target representation. In Experiment 1, observers previewed four photorealistic objects and were cued to remember the two objects appearing to the left or right of central fixation; Experiment 2 was identical except that observers previewed two photorealistic objects and were cued to remember one. CDA was measured during a delay following preview offset but before onset of a four-object search array. One of the targets was always present, and observers were asked to make an eye movement to it and press a button. We found lower magnitude CDA on trials when the initial search saccade was directed to the target (strong guidance) compared to when it was not (weak guidance). This difference also tended to be larger shortly before search-display onset and was largely unaffected by VWM item-capacity limits or number of previews. Moreover, the difference between mean strong- and weak-guidance CDA was proportional to the increase in search time between mean strong-and weak-guidance trials (as measured by time-to-target and reaction-time difference scores). Contrary to most search models, our data suggest that trials resulting in the maintenance of more target features results in poor search guidance to a target. We interpret these counterintuitive findings as evidence for strong search guidance using a small set of highly discriminative target features that remain after pruning from a larger set of features, with the load imposed on VWM varying with this feature-consolidation process. PMID:24599946

  18. Could low level laser therapy and highly active antiretroviral therapy lead to complete eradication of HIV-1 in vitro?

    Science.gov (United States)

    Lugongolo, Masixole Yvonne; Manoto, Sello Lebohang; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

    2017-02-01

    Human immunodeficiency virus (HIV-1) infection remains a major health problem despite the use of highly active antiretroviral therapy (HAART), which has greatly reduced mortality rates. Due to the unavailability of an effective vaccine or a treatment that would completely eradicate the virus, the quest for new and combination therapies continues. In this study we explored the influence of Low Level Laser Therapy (LLLT) in HIV-1 infected and uninfected cells. Literature reports LLLT as widely used to treat different medical conditions such as diabetic wounds, sports injuries and others. The technique involves exposure of cells or tissue to low levels of red and near infrared laser light. Both HIV infected and uninfected cells were laser irradiated at a wavelength of 640 nm with fluencies ranging from 2 to 10 J/cm2 and cellular responses were assessed 24 hours post laser treatment. In our studies, laser therapy had no inhibitory effects in HIV-1 uninfected cells as was indicated by the cell morphology and proliferation results. However, laser irradiation enhanced cell apoptosis in HIV-1 infected cells as the laser fluencies increased. This led to further studies in which laser irradiation would be conducted in the presence of HAART to determine whether HAART would minimise the detrimental effects of laser irradiation in infected cells.

  19. High hydrostatic pressure activates gene expression that leads to ethanol production enhancement in a Saccharomyces cerevisiae distillery strain

    Science.gov (United States)

    Bravim, Fernanda; Lippman, Soyeon I.; da Silva, Lucas F.; Souza, Diego T.; Fernandes, A. Alberto R.; Masuda, Claudio A.; Broach, James R.

    2016-01-01

    High hydrostatic pressure (HHP) is a stress that exerts broad effects on microorganisms with characteristics similar to those of common environmental stresses. In this study, we aimed to identify genetic mechanisms that can enhance alcoholic fermentation of wild Saccharomyces cerevisiae isolated from Brazilian spirit fermentation vats. Accordingly, we performed a time course microarray analysis on a S. cerevisiae strain submitted to mild sublethal pressure treatment of 50 MPa for 30 min at room temperature, followed by incubation for 5, 10 and 15 min without pressure treatment. The obtained transcriptional profiles demonstrate the importance of post-pressurisation period on the activation of several genes related to cell recovery and stress tolerance. Based on these results, we over-expressed genes strongly induced by HHP in the same wild yeast strain and identified genes, particularly SYM1, whose over-expression results in enhanced ethanol production and stress tolerance upon fermentation. The present study validates the use of HHP as a biotechnological tool for the fermentative industries. PMID:22915193

  20. Subfailure overstretch injury leads to reversible functional impairment and purinergic P2X7 receptor activation in intact vascular tissue

    Directory of Open Access Journals (Sweden)

    Weifeng Luo

    2016-09-01

    Full Text Available Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities.

  1. Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon.

    Directory of Open Access Journals (Sweden)

    Natalia López-del Hoyo

    Full Text Available Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout and gain-of-function (transgenic overexpression mouse models of GCAP2. Rod synaptic ribbons in GCAPs-/- mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs-/- background (GCAP2 expression in the absence of endogenous GCAP1 had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of

  2. A case of delayed cardiac perforation of active ventricular lead

    Directory of Open Access Journals (Sweden)

    Hangyuan Guo

    2011-12-01

    Full Text Available A 65-year-old man was admitted as for one month of repetitive dizziness and one episode of syncope. Electrocardiogram showed sinus bradycardia and his Holter monitoring also showed sinus bradycardia with sinus arrest, sino-atrial block and a longest pause of 4.3 s. Then sick sinus syndrome and Adam-Stokes syndrome were diagnosed. Then a dual chamber pacemaker (Medtronic SDR303 was implanted and the parameters were normal by detection. The patient was discharged 1 week later with suture removed. Then 1.5 month late the patient was presented to hospital once again for sudden onset of chest pain with exacerbation after taking deep breath. Pacemaker programming showed both pacing and sensing abnormality with threshold of?5.0V and resistance of 1200?. Lead perforation was revealed by chest X-ray and confirmed by echocardiogram. Considering the fact that there was high risk to remove ventricular lead, spiral tip of previous ventricular lead was withdrew followed by implantation of a new ventricular active lead to the septum. Previous ventricular lead was maintained. As we know that the complications of lead perforation in the clinic was rare. Here we discuss the clinical management and the possible reasons for cardiac perforation of active ventricular lead.

  3. 37 years of scientific activity in a Biochemistry Department in Brazil: patterns of growth and factors leading to increased productivity.

    Science.gov (United States)

    Gomes, Urubatã E; Oliveira, Diogo L de; Berti, Luciana C; Amaral, Olavo; Souza, Diogo O; Wofchuk, Susana T

    2011-09-01

    Scientific activity in Brazil has experienced an accelerated growth in the past decades, with an increase in productivity that greatly surpasses the international average. This growth has occurred mostly at the expense of centers of excellence in public universities, which account for the vast majority of the country's scientific output. The aim of this study was to evaluate the production of the Department of Biochemistry of a large public university in southern Brazil (Universidade Federal do Rio Grande do Sul), as well as to identify internal and external policies that have influenced this growing production profile. We have performed a historical analysis of the scientific output of this Department of Biochemistry, which accounts for a considerable share of the indexed scientific production at this university. By focusing on the temporal course of its growth and drawing correlations between scientific output and important events in the history of the Department of Biochemistry and of the Brazilian science policies, we concluded that internal factors (as the creation of a postgraduation program, collaboration among researchers, experienced abroad researchers, qualification of faculty members) and external factors (as investments in the postgraduate education, the establishment of national scientific policies, such as financial stimuli for productive researchers and evaluation systems) influence scientific productivity in Brazil.

  4. 75 FR 26268 - Agency Information Collection Activities: Permit To Transfer Containers to a Container Station

    Science.gov (United States)

    2010-05-11

    ... Containers to a Container Station AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... concerning the: Permit to Transfer Containers to a Container Station. This request for comment is being made... Containers to a Container Station. OMB Number: 1651-0049. Form Number: None. Abstract: This information...

  5. Elevation leads to altruistic behavior.

    Science.gov (United States)

    Schnall, Simone; Roper, Jean; Fessler, Daniel M T

    2010-03-01

    Feelings of elevation, elicited by witnessing another person perform a good deed, have been hypothesized to motivate a desire to help others. However, despite growing interest in the determinants of prosocial behavior, there is only limited evidence that elevation leads to increases in altruistic behavior. In two experiments, we tested the relationship between elevation and helping behavior. Prior to measuring helping behavior, we measured elevation among participants in an elevation-inducing condition and control conditions in order to determine whether witnessing altruistic behavior elicited elevation. In Experiment 1, participants experiencing elevation were more likely to volunteer for a subsequent unpaid study than were participants in a neutral state. In Experiment 2, participants experiencing elevation spent approximately twice as long helping the experimenter with a tedious task as participants experiencing mirth or a neutral emotional state. Further, feelings of elevation, but not feelings of amusement or happiness, predicted the amount of helping. Together, these results provide evidence that witnessing another person's altruistic behavior elicits elevation, a discrete emotion that, in turn, leads to tangible increases in altruism.

  6. Attention to Physical Activity-Equivalent Calorie Information on Nutrition Facts Labels: An Eye-Tracking Investigation.

    Science.gov (United States)

    Wolfson, Julia A; Graham, Dan J; Bleich, Sara N

    2017-01-01

    Investigate attention to Nutrition Facts Labels (NFLs) with numeric only vs both numeric and activity-equivalent calorie information, and attitudes toward activity-equivalent calories. An eye-tracking camera monitored participants' viewing of NFLs for 64 packaged foods with either standard NFLs or modified NFLs. Participants self-reported demographic information and diet-related attitudes and behaviors. Participants came to the Behavioral Medicine Lab at Colorado State University in spring, 2015. The researchers randomized 234 participants to view NFLs with numeric calorie information only (n = 108) or numeric and activity-equivalent calorie information (n = 126). Attention to and attitudes about activity-equivalent calorie information. Differences by experimental condition and weight loss intention (overall and within experimental condition) were assessed using t tests and Pearson's chi-square tests of independence. Overall, participants viewed numeric calorie information on 20% of NFLs for 249 ms. Participants in the modified NFL condition viewed activity-equivalent information on 17% of NFLs for 231 ms. Most participants indicated that activity-equivalent calorie information would help them decide whether to eat a food (69%) and that they preferred both numeric and activity-equivalent calorie information on NFLs (70%). Participants used activity-equivalent calorie information on NFLs and found this information helpful for making food decisions. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  7. 75 FR 43536 - Agency Information Collection Activities: Permit To Transfer Containers to a Container Station

    Science.gov (United States)

    2010-07-26

    ... Containers to a Container Station AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... review and approval in accordance with the Paperwork Reduction Act: Permit to Transfer Containers to a Container Station. This is a proposed extension of an information collection that was previously approved...

  8. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    Science.gov (United States)

    Morrish, F; Isern, N; Sadilek, M; Jeffrey, M; Hockenbery, D M

    2009-07-09

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell-cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell-cycle entry is unknown. Here, we report the metabolic fates of [U-(13)C] glucose in serum-stimulated myc(-/-) and myc(+/+) fibroblasts by (13)C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased (13)C labeling of ribose sugars, purines and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked N-acetylglucosamine protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing function for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its function in directing metabolic networks required for cell proliferation.

  9. All roads lead to Meyrin

    CERN Multimedia

    Communication locale

    2011-01-01

    Tous les chemins mènent à Meyrin - All roads lead to Meyrin From 29 September to 16 October, 2011, come to the Salle Antoine Verchère in Meyrin for Tous les chemins mènent à Meyrin. The celebration will include an exposition as well as a theatrical performance about Meyrin, the first satellite city in Switzerland. With the help of the memories and testimonies from the people of Meyrin, Tous les chemins mènent à Meyrin is putting the collective memories of the commune on display. It is an occasion for everyone, whether you're from near or far, to find out how all the roads lead to Meyrin.  Salle Antoine-Verchère Route de Meyrin 294 – 1217 Meyrin Tram 18 – Stop: Meyrin Village Thursdays / Fridays / Saturdays at 8pm Sundays at 5pm Regular ticket: CHF 15.- Concession ticket (students, chômeurs, AVS, AI): CHF 12.- Children up to 16: CHF 10.- Family ticket: CHF 35.-

  10. Extending dynamic segmentation with lead generation : A latent class Markov analysis of financial product portfolios

    NARCIS (Netherlands)

    Paas, L.J.; Bijmolt, T.H.A.; Vermunt, J.K.

    2004-01-01

    A recent development in marketing research concerns the incorporation of dynamics in consumer segmentation.This paper extends the latent class Markov model, a suitable technique for conducting dynamic segmentation, in order to facilitate lead generation.We demonstrate the application of the latent

  11. Revenue generation in the information era: Opportunities and challenges

    Directory of Open Access Journals (Sweden)

    Sreelata Jonnalagedda

    2011-03-01

    Full Text Available In an information economy, innovative revenue generating models are as critical for the sustenance of a firm as is bringing cutting edge technology to the market. In its first part, this article surveys the characteristics of the information goods market and identifies the opportunities and challenges that the information era presents. Further, it surveys the existing business models for information goods and maps them to the market characteristics to arrive at the viability of these models. The second part of the article presents the views and experiences of a panel of practitioners who face these challenges in the field of information goods.

  12. NOC/oFQ activates PKC and generates superoxide to impair hypotensive cerebrovasodilation after hypoxia/ischemia.

    Science.gov (United States)

    Armstead, William

    2002-01-01

    Previous studies have observed that hypotensive pial artery dilation was blunted following global cerebral ischemia in the piglet. In unrelated studies, superoxide (O-2) contributed to impaired hypotensive cerebrovasodilation following traumatic brain injury in the rat while the opioid nociceptin/orphanin FQ (NOC/oFQ) generated O-2 via activation of protein kinase C in the piglet. This study determined the contribution of NOC/oFQ, PKC activation and O-2 generation in hypoxic ischemic hypotensive cerebrovasodilation impairment. Anesthetized newborn pigs equipped with a closed cranial window were used. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia, via inhalation of nitrogen, decreased PO2 to 34I3 mmHg. Topical NOC/oFQ (10-10M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44I2%) induced pial artery dilation (33I1 vs 19I2%). Coadministration of the PKC inhibitor chelerythrine (10-7M) or the O-2 scavenger polyethylene glycol superoxide dismutase and catalase (SODCAT) with NOC/oFQ (10-10M) partially prevented hypotensive pial dilation impairment (34I2 vs 28I1% for SODCAT). Hypotensive pial artery dilation was blunted by hypoxia/ischemia but such dilation was partially protected by the NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1-13) NH2 (10-6M), chelerythine or SODCAT (34I1 vs 7I2 vs 21I2% for sham, H/I and H/I + SODCAT, respectively). These data show that PKC activation and generation of O-2 contributes to hypoxia/ischemia impairment of hypotensive pial artery dilation. These data suggest that NOC/oFQ activates PKC and generates O-2 to impair hypotensive cerebrovasodilation after hypoxia/ischemia.

  13. SOPHIE: Social, Open Pro-active Hub for Information Exchange to Support Intelligence Communities

    NARCIS (Netherlands)

    Streefkerk, J.W.; Eikelboom, A.; Paulissen, R.; Bemmel, I.E. van; Hemmer, A.F.; Venrooij, W.; Hollander, C.J. den

    2014-01-01

    Military intelligence communities need to collect, process and disseminate information as quickly and efficiently as possible, for example in answering requests for information by commanders. Currently, the flow of information between the field and intelligence communities is hampered by disparities

  14. Use of Microarray Datasets to generate Caco-2-dedicated Networks and to identify Reporter Genes of Specific Pathway Activity.

    Science.gov (United States)

    Venkatasubramanian, Prashanna Balaji; Toydemir, Gamze; de Wit, Nicole; Saccenti, Edoardo; Martins Dos Santos, Vitor A P; van Baarlen, Peter; Wells, Jerry M; Suarez-Diez, Maria; Mes, Jurriaan J

    2017-07-28

    Intestinal epithelial cells, like Caco-2, are commonly used to study the interaction between food, other luminal factors and the host, often supported by microarray analysis to study the changes in gene expression as a result of the exposure. However, no compiled dataset for Caco-2 has ever been initiated and Caco-2-dedicated gene expression networks are barely available. Here, 341 Caco-2-specific microarray samples were collected from public databases and from in-house experiments pertaining to Caco-2 cells exposed to pathogens, probiotics and several food compounds. Using these datasets, a gene functional association network specific for Caco-2 was generated containing 8937 nodes 129711 edges. Two in silico methods, a modified version of biclustering and the new Differential Expression Correlation Analysis, were developed to identify Caco-2-specific gene targets within a pathway of interest. These methods were subsequently applied to the AhR and Nrf2 signalling pathways and altered expression of the predicted target genes was validated by qPCR in Caco-2 cells exposed to coffee extracts, known to activate both AhR and Nrf2 pathways. The datasets and in silico method(s) to identify and predict responsive target genes can be used to more efficiently design experiments to study Caco-2/intestinal epithelial-relevant biological processes.

  15. Using Molecular Initiating Events To Generate 2D Structure-Activity Relationships for Toxicity Screening.

    Science.gov (United States)

    Allen, Timothy E H; Liggi, Sonia; Goodman, Jonathan M; Gutsell, Steve; Russell, Paul J

    2016-10-17

    Molecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties that allow them to exhibit this behavior, be these properties stereochemical, electronic, or otherwise. In an attempt to discover some of these chemical characteristics, we have constructed structural alert-style structure-activity relationships (SARs) to computationally predict MIEs. This work utilizes chemical informatics approaches, searching the ChEMBL database for molecules that bind to a number of pharmacologically important human toxicology targets, including G-protein coupled receptors, enzymes, ion channels, nuclear receptors, and transporters. By screening these compounds to find common 2D fragments and combining this approach with a good understanding of the literature, bespoke 2D structural alerts have been written. These SARs form the beginning of a tool for screening novel chemicals to establish the kind of interactions that they may be able to make in humans. These SARs have been run through an internal validation to test their quality, and the results of this are also discussed. MIEs have proven to be difficult to find and characterize, but we believe we have taken a key first step with this work.

  16. 75 FR 5638 - Information Collection Activities

    Science.gov (United States)

    2010-02-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration Information Collection Activities AGENCY: Pipeline... affected agencies have an opportunity to comment on information collection and recordkeeping activities...

  17. Lead activity in Pb-Sb-Bi alloys

    Directory of Open Access Journals (Sweden)

    A. S. Kholkina

    2014-11-01

    Full Text Available The present work is devoted to the study of lead thermodynamic activity in the Pb-Sb-Bi alloys. The method for EMF measurements of the concentration cell: (–Pb|KCl-PbCl2¦¦KCl-PbCl2|Pb-(Sb-Bi(+ was used. The obtained concentration dependences of the galvanic cell EMF are described by linear equations. The lead activity in the ternary liquid-metal alloy demonstrates insignificant negative deviations from the behavior of ideal solutions.

  18. Relationship between caregivers' income generation activities and ...

    African Journals Online (AJOL)

    Enhancing Child Nutrition through Animal Source Food Management (ENAM) project provided financial and technical support for caregivers' Income Generation Activities (IGA) with the aim of increasing their access to Animal Source Foods (ASF) for improved child nutrition. Using baseline data from the ENAM project, this ...

  19. The information activity of rail passenger information staff: a foundation for information system requirements

    Directory of Open Access Journals (Sweden)

    Martin Rose

    2006-01-01

    Full Text Available Introduction. This paper examines the goal-directed information activity of passenger information staff, working in the dynamic environment of rail network control. The explicit aim is to define a meaningful set of information system requirements. The report shows how dynamic situations may lead us to question a number of established theories of information science. Method. Passenger information officers (PIOs were observed on duty within the rail command and control headquarters. Observation sessions totally eight hours involved the manual recording of sequential information flows and the associated activity of PIOs. A semi-structured management interview was also conducted to provide further insight into the organizational context. Analysis. A viewpoint-oriented analysis technique was used to analyse sequential data captured during observation sessions. Event sequences that represent and explain the viewpoints were identified and elaborated into detailed scenario descriptions. Results. The analysis both supports and contests a number of established theories from information science. Additionally, a range of 'mandatory' and 'desirable' system requirements are derived from the scenario and viewpoint analyses. Conclusion. Dynamic situations have a significant impact on information behaviour which is not always predicted by current theories of information science.

  20. Information Portals: The Next Generation Catalog

    Science.gov (United States)

    Allison, DeeAnn

    2010-01-01

    Libraries today face an increasing challenge: to provide relevant information to diverse populations with differing needs while competing with Web search engines like Google. In 2009, a large group of libraries, including the University of Nebraska-Lincoln Libraries, joined with Innovative Interfaces as development partners to design a new type of…

  1. 78 FR 16519 - Agency Information Collection Activities: Application for Advance Permission To Return to...

    Science.gov (United States)

    2013-03-15

    ... Federal eRulemaking Portal Web site at www.Regulations.gov under e-Docket ID number USCIS-2006-0070; (2... instructions, or additional information, please visit the Federal eRulemaking Portal site at: http://www... comments or material, all submissions will be posted, without change, to the Federal eRulemaking Portal at...

  2. Preparing the Next Generations of Technology Project Managers to Lead through Knowledge Sharing: A Case Study at a Large Transportation Company

    Science.gov (United States)

    Kargbo, Michelle

    2013-01-01

    The purpose of this research was to identify knowledge transfer gaps and current practices, prepare current project managers to accept the challenges associated with leadership opportunities that are coming available due to retirements through cross training efforts and succession planning, and to identify the proper management of knowledge…

  3. Generating 3D hyperspectral information with lightweight UAV snapshot cameras for vegetation monitoring: From camera calibration to quality assurance

    Science.gov (United States)

    Aasen, Helge; Burkart, Andreas; Bolten, Andreas; Bareth, Georg

    2015-10-01

    This paper describes a novel method to derive 3D hyperspectral information from lightweight snapshot cameras for unmanned aerial vehicles for vegetation monitoring. Snapshot cameras record an image cube with one spectral and two spatial dimensions with every exposure. First, we describe and apply methods to radiometrically characterize and calibrate these cameras. Then, we introduce our processing chain to derive 3D hyperspectral information from the calibrated image cubes based on structure from motion. The approach includes a novel way for quality assurance of the data which is used to assess the quality of the hyperspectral data for every single pixel in the final data product. The result is a hyperspectral digital surface model as a representation of the surface in 3D space linked with the hyperspectral information emitted and reflected by the objects covered by the surface. In this study we use the hyperspectral camera Cubert UHD 185-Firefly, which collects 125 bands from 450 to 950 nm. The obtained data product has a spatial resolution of approximately 1 cm for the spatial and 21 cm for the hyperspectral information. The radiometric calibration yields good results with less than 1% offset in reflectance compared to an ASD FieldSpec 3 for most of the spectral range. The quality assurance information shows that the radiometric precision is better than 0.13% for the derived data product. We apply the approach to data from a flight campaign in a barley experiment with different varieties during the growth stage heading (BBCH 52 - 59) to demonstrate the feasibility for vegetation monitoring in the context of precision agriculture. The plant parameters retrieved from the data product correspond to in-field measurements of a single date field campaign for plant height (R2 = 0.7), chlorophyll (BGI2, R2 = 0.52), LAI (RDVI, R2 = 0.32) and biomass (RDVI, R2 = 0.29). Our approach can also be applied for other image-frame cameras as long as the individual bands of the

  4. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, Paul E [ORNL; Giannone, Richard J [ORNL; Xiong, Weili [ORNL; Hettich, Robert {Bob} L [ORNL

    2014-01-01

    Contemporary microbial ecology studies usually employ one or more omics approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other meta-omic approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  5. Using Active Learning to Identify Health Information Technology Related Patient Safety Events.

    Science.gov (United States)

    Fong, Allan; Howe, Jessica L; Adams, Katharine T; Ratwani, Raj M

    2017-01-18

    The widespread adoption of health information technology (HIT) has led to new patient safety hazards that are often difficult to identify. Patient safety event reports, which are self-reported descriptions of safety hazards, provide one view of potential HIT-related safety events. However, identifying HIT-related reports can be challenging as they are often categorized under other more predominate clinical categories. This challenge of identifying HIT-related reports is exacerbated by the increasing number and complexity of reports which pose challenges to human annotators that must manually review reports. In this paper, we apply active learning techniques to support classification of patient safety event reports as HIT-related. We evaluated different strategies and demonstrated a 30% increase in average precision of a confirmatory sampling strategy over a baseline no active learning approach after 10 learning iterations.

  6. Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts.

    Directory of Open Access Journals (Sweden)

    Sunil C Kaul

    Full Text Available Ashwagandha (Withania somnifera is an Ayurvedic herb commonly used in world-renowned traditional Indian home medicine system. Roots of Ashwagandha have been traditionally known to possess a variety of therapeutic and health promoting potentials that have not been sufficiently supported by laboratory studies. Nevertheless, most, if not all, of the preventive and therapeutic potentials have been assigned to its bioactive components, steroidal alkaloids and lactones. In contrast to the traditional use of roots, we have been exploring bioactivities in leaves of Ashwagandha. Here, we report that the leaves possess higher content of active Withanolides, Withaferin-A (Wi-A and Withanone (Wi-N, as compared to the roots. We also established, for the first time, hydroponic cultivation of Ashwagandha and investigated the effect of various cultivation conditions on the content of Wi-A and Wi-N by chemical analysis and bioassays. We report that the Withanone/Withaferin A-rich leaves could be obtained by manipulating light condition during hydroponic cultivation. Furthermore, we recruited cyclodextrins to prepare extracts with desired ratio of Wi-N and Wi-A. Hydroponically grown Ashwagandha and its extracts with high ratio of withanolides are valuable for cancer treatment.

  7. Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts.

    Science.gov (United States)

    Kaul, Sunil C; Ishida, Yoshiyuki; Tamura, Kazuya; Wada, Teruo; Iitsuka, Tomoko; Garg, Sukant; Kim, Mijung; Gao, Ran; Nakai, Shoichi; Okamoto, Youji; Terao, Keiji; Wadhwa, Renu

    2016-01-01

    Ashwagandha (Withania somnifera) is an Ayurvedic herb commonly used in world-renowned traditional Indian home medicine system. Roots of Ashwagandha have been traditionally known to possess a variety of therapeutic and health promoting potentials that have not been sufficiently supported by laboratory studies. Nevertheless, most, if not all, of the preventive and therapeutic potentials have been assigned to its bioactive components, steroidal alkaloids and lactones. In contrast to the traditional use of roots, we have been exploring bioactivities in leaves of Ashwagandha. Here, we report that the leaves possess higher content of active Withanolides, Withaferin-A (Wi-A) and Withanone (Wi-N), as compared to the roots. We also established, for the first time, hydroponic cultivation of Ashwagandha and investigated the effect of various cultivation conditions on the content of Wi-A and Wi-N by chemical analysis and bioassays. We report that the Withanone/Withaferin A-rich leaves could be obtained by manipulating light condition during hydroponic cultivation. Furthermore, we recruited cyclodextrins to prepare extracts with desired ratio of Wi-N and Wi-A. Hydroponically grown Ashwagandha and its extracts with high ratio of withanolides are valuable for cancer treatment.

  8. Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cells

    DEFF Research Database (Denmark)

    Andersen, Thomas L; Søe, Kent; Søndergaard, Teis Esben

    2010-01-01

    Osteolytic lesions are a hallmark of multiple myeloma. They are due to the hyperactivity of bone resorbing osteoclasts and hypoactivity of bone forming osteoblasts, in response to neighbouring myeloma cells. This study identified a structure that deeply affects this response, because of its impact...... on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy over bone...... remodelling compartment (BRC). These canopies are frequently disrupted in myeloma, and this disruption correlates with increased proximity and density of myeloma cells. In vitro evidence indicates that this disruption may be due to direct contact between myeloma and BRC canopy cells. Importantly...

  9. 37 years of scientific activity in a Biochemistry Department in Brazil: patterns of growth and factors leading to increased productivity

    Directory of Open Access Journals (Sweden)

    Urubatã E. Gomes

    2011-09-01

    Full Text Available Scientific activity in Brazil has experienced an accelerated growth in the past decades, with an increase in productivity that greatly surpasses the international average. This growth has occurred mostly at the expense of centers of excellence in public universities, which account for the vast majority of the country's scientific output. The aim of this study was to evaluate the production of the Department of Biochemistry of a large public university in southern Brazil (Universidade Federal do Rio Grande do Sul, as well as to identify internal and external policies that have influenced this growing production profile. We have performed a historical analysis of the scientific output of this Department of Biochemistry, which accounts for a considerable share of the indexed scientific production at this university. By focusing on the temporal course of its growth and drawing correlations between scientific output and important events in the history of the Department of Biochemistry and of the Brazilian science policies, we concluded that internal factors (as the creation of a postgraduation program, collaboration among researchers, experienced abroad researchers, qualification of faculty members and external factors (as investments in the postgraduate education, the establishment of national scientific policies, such as financial stimuli for productive researchers and evaluation systems influence scientific productivity in Brazil.A atividade científica no Brasil apresentou um crescimento acelerado nas últimas décadas, com um aumento na produtividade que ultrapassou os valores médios internacionais. Este crescimento tem ocorrido através dos centros de excelência em pesquisa nas Universidades Públicas, as quais são responsáveis pela maior parte da produção científica do país. O presente estudo tem como objetivo avaliar a produção do Departamento de Bioquímica de uma grande universidade pública do sul do Brasil (Universidade Federal

  10. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline

    DEFF Research Database (Denmark)

    Hardies, Katia; Cai, Yiying; Jardel, Claude

    2016-01-01

    with intractable epilepsy and tau pathology. We performed whole exome or genome sequencing in three independent sib pairs with early onset refractory seizures and progressive neurological decline, and identified novel segregating recessive SYNJ1 defects. A homozygous missense variant resulting in an amino acid...... function, our results provide evidence that a critical reduction of the dual phosphatase activity of SYNJ1 underlies a severe disorder with neonatal refractory epilepsy and a neurodegenerative disease course. These findings further expand the clinical spectrum of synaptic dysregulation in patients...

  11. Next to Leading Logarithms and the PHOTOS Monte Carlo

    CERN Document Server

    Golonka, P

    2007-01-01

    With the approaching start-up of the experiments at LHC, the urgency to quantify systematic uncertainties of the generators, used in the interpretation of the data, is becoming pressing. The PHOTOS Monte Carlo program is often used for the simulationof experimental, selection-sensitive, QED radiative corrections in decays of Z bosons and other heavy resonances and particles. Thanks to its complete phase-space coverage it is possible, with no approximations for any decay channel, to implement the matrix-element. The present paper will be devoted to those parts of the next-to-leading order corrections for Z decays which are normally missing in PHOTOS. The analytical form of the exact and truncated (standard) kernel used in PHOTOS will be explicitly given. The correction, being the ratio of the exact to the approximate kernel, can be activated as an optional contribution to the internal weight of PHOTOS. To calculate the weight, the information on the effective Born-level Z/gamma* couplings and even directions o...

  12. PI3-kinase γ promotes Rap1a-mediated activation of myeloid cell integrin α4β1, leading to tumor inflammation and growth.

    Directory of Open Access Journals (Sweden)

    Michael C Schmid

    Full Text Available Tumor inflammation, the recruitment of myeloid lineage cells into the tumor microenvironment, promotes angiogenesis, immunosuppression and metastasis. CD11b+Gr1lo monocytic lineage cells and CD11b+Gr1hi granulocytic lineage cells are recruited from the circulation by tumor-derived chemoattractants, which stimulate PI3-kinase γ (PI3Kγ-mediated integrin α4 activation and extravasation. We show here that PI3Kγ activates PLCγ, leading to RasGrp/CalDAG-GEF-I&II mediated, Rap1a-dependent activation of integrin α4β1, extravasation of monocytes and granulocytes, and inflammation-associated tumor progression. Genetic depletion of PLCγ, CalDAG-GEFI or II, Rap1a, or the Rap1 effector RIAM was sufficient to prevent integrin α4 activation by chemoattractants or activated PI3Kγ (p110γCAAX, while activated Rap (RapV12 promoted constitutive integrin activation and cell adhesion that could only be blocked by inhibition of RIAM or integrin α4β1. Similar to blockade of PI3Kγ or integrin α4β1, blockade of Rap1a suppressed both the recruitment of monocytes and granulocytes to tumors and tumor progression. These results demonstrate critical roles for a PI3Kγ-Rap1a-dependent pathway in integrin activation during tumor inflammation and suggest novel avenues for cancer therapy.

  13. Can systemically generated reactive oxygen species help to monitor disease activity in generalized vitiligo? A pilot study

    Directory of Open Access Journals (Sweden)

    Richeek Pradhan

    2014-01-01

    Full Text Available Background: Generalized vitiligo is a disease with unpredictable bursts of activity, goal of treatment during the active phase being to stabilize the lesions. This emphasizes the need for a prospective marker for monitoring disease activity to help decide the duration of therapy. Aims and Objectives: In the present study, we examined whether reactive oxygen species (ROS generated in erythrocytes can be translated into a marker of activity in vitiligo. Materials and Methods: Level of intracellular ROS was measured flow cytometrically in erythrocytes from venous blood of 21 patients with generalized vitiligo and 21 healthy volunteers using the probe dichlorodihydrofluorescein diacetate. Results: The levels of ROS differed significantly between patients and healthy controls, as well as between active versus stable disease groups. In the active disease group, ROS levels were significantly lower in those being treated with systemic steroids than those that were not. ROS levels poorly correlated with disease duration or body surface area involved. Conclusion: A long-term study based on these findings can be conducted to further validate the potential role of ROS in monitoring disease activity vitiligo.

  14. IAEA activities on steam generator life management

    Energy Technology Data Exchange (ETDEWEB)

    Gueorguiev, B.; Lyssakov, V.; Trampus, P. [International Atomic Energy Agency, Div. of Nuclear Power, Vienna (Austria)

    2002-07-01

    The International Atomic Energy Agency (IAEA) carries out a set of activities in the field of Nuclear Power Plant (NPP) life management. Main activities within this area are implemented through the Technical Working Group on Life Management of NPPs, and mostly concentrated on studies of understanding mechanisms of degradation and their monitoring, optimisation of maintenance management, economic aspects, proven practices of and approaches to plant life management including decommissioning. The paper covers two ongoing activities related to steam generator life management: the International Database on NPP Steam Generators and the Co-ordinated Research Project on Verification of WWER Steam Generator Tube Integrity (WWER is the Russian designed PWR). The lifetime assessment of main components relies on an ability to assess their condition and predict future degradation trends, which to a large extent is dependent on the availability of relevant data. Effective management of ageing and degradation processes requires a large amount of data. Several years ago the IAEA started to work on the International Database on NPP Life Management. This is a multi-module database consisting of modules such as reactor pressure vessels materials, piping, steam generators, and concrete structures. At present the work on pressure vessel materials, on piping as well as on steam generator is completed. The paper will present the concept and structure of the steam generator module of the database. In countries operating WWER NPPs, there are big differences in the eddy current inspection strategy and practice as well as in the approach to steam generator heat exchanger tube structural integrity assessment. Responding to the need for a co-ordinated research to compare eddy current testing results with destructive testing using pulled out tubes from WWER steam generators, the IAEA launched this project. The main objectives of the project are to summarise the operating experiences of WWER

  15. Darwinian selection leads to Gaia.

    Science.gov (United States)

    Staley, Mark

    2002-09-07

    The Gaia hypothesis, in its strongest form, states that the Earth's atmosphere, oceans, and biota form a tightly coupled system that maintains environmental conditions close to optimal for life. According to Gaia theory, optimal conditions are intrinsic, immutable properties of living organisms. It is assumed that the role of Darwinian selection is to favor organisms that act to stabilize environmental conditions at these optimal levels. In this paper, an alternative form of Gaia theory based on more traditional Darwinian principles is proposed. In the new approach, environmental regulation is a consequence of population dynamics, not Darwinian selection. The role of selection is to favor organisms that are best adapted to prevailing environmental conditions. However, the environment is not a static backdrop for evolution, but is heavily influenced by the presence of living organisms. The resulting co-evolving dynamical process eventually leads to the convergence of equilibrium and optimal conditions. A simple Daisyworld model is used to illustrate this convergence phenomenon. Sensitivity analysis of the Daisyworld model suggests that in stable ecosystems, the convergence of equilibrium and optimal conditions is inevitable, provided there are no externally driven shocks to the system. The end result may appear to be the product of a cooperative venture, but is in fact the outcome of Darwinian selection acting upon "selfish" organisms.

  16. Different brain activity in response to emotional faces alone and augmented by contextual information.

    Science.gov (United States)

    Lee, Kyung Hwa; Siegle, Greg J

    2014-11-01

    This study examined the extent to which emotional face stimuli differ from the neural reactivity associated with more ecological contextually augmented stimuli. Participants were scanned when they viewed contextually rich pictures depicting both emotional faces and context, and pictures of emotional faces presented alone. Emotional faces alone were more strongly associated with brain activity in paralimbic and social information processing regions, whereas emotional faces augmented by context were associated with increased and sustained activity in regions potentially representing increased complexity and subjective emotional experience. Furthermore, context effects were modulated by emotional intensity and valence. These findings suggest that cortical elaboration that is apparent in contextually augmented stimuli may be missed in studies of emotional faces alone, whereas emotional faces may more selectively recruit limbic reactivity. Copyright © 2014 Society for Psychophysiological Research.

  17. Validation of the Monte Carlo model developed to assess the activity generated in control rods of a BWR

    Energy Technology Data Exchange (ETDEWEB)

    Rodenas, Jose, E-mail: jrodenas@iqn.upv.e [Departamento de Ingenieria Quimica y Nuclear, Universidad Politecnica de Valencia, Apartado 22012, E-46071 Valencia (Spain); Abarca, Agustin; Gallardo, Sergio [Departamento de Ingenieria Quimica y Nuclear, Universidad Politecnica de Valencia, Apartado 22012, E-46071 Valencia (Spain); Sollet, Eduardo [Servicio de Proteccion Radiologica, Central Nuclear de Cofrentes, Valencia (Spain)

    2010-07-21

    Control rods are activated by neutron reactions into the reactor. The activation is produced mainly in stainless steel and its impurities. The dose produced by this activity is not important inside the reactor, but it has to be taken into account when the rod is withdrawn from it. The neutron activation has been modeled with the MCNP5 code based on the Monte Carlo method. The number of reactions obtained with the code can be converted into activity. In this work, a detailed model of the control rod has been developed considering all its components: handle, tubes, gain, and central core. On the other hand, the rod has been divided into 5 zones in order to consider the different axial exposition to neutron flux into the reactor. Results of the Monte Carlo simulation for the neutron activation constitute a gamma source in the control rod. With this source, applying again the Monte Carlo method, doses at certain distance of the rod have been calculated. Comparison of calculated doses with experimental measurements leads to the validation of the model developed.

  18. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    Science.gov (United States)

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies. © The Author(s) 2016.

  19. Validity of the Katz Index to assess activities of daily living by informants in neuropathological studies

    Directory of Open Access Journals (Sweden)

    Renata Eloah de Lucena Ferretti-Rebustini

    2015-12-01

    Full Text Available Abstract OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG database. Sample was divided in two subsamples for the analysis (N=325, each and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR. Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.

  20. Informal face-to-face interaction improves mood state reflected in prefrontal cortex activity

    Directory of Open Access Journals (Sweden)

    Jun-Ichiro eWatanabe

    2016-05-01

    Full Text Available Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS.We also observed that the verbal WM task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC activity accompanied by working memory (WM tasks measured by near-infrared spectroscopy (NIRS.

  1. Rapid Microsatellite Marker Development Using Next Generation Pyrosequencing to Inform Invasive Burmese Python—Python molurus bivittatus—Management

    Directory of Open Access Journals (Sweden)

    Kristen M. Hart

    2013-02-01

    Full Text Available Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus, is one of the most notable invasive species in the US, due to the threat it poses to imperiled species and the Greater Everglades ecosystem. To address population structure and relatedness, next generation sequencing was used to rapidly produce species-specific microsatellite loci. The Roche 454 GS-FLX Titanium platform provided 6616 di-, tri- and tetra-nucleotide repeats in 117,516 sequences. Using stringent criteria, 24 of 26 selected tri- and tetra-nucleotide loci were polymerase chain reaction (PCR amplified and 18 were polymorphic. An additional six cross-species loci were amplified, and the resulting 24 loci were incorporated into eight PCR multiplexes. Multi-locus genotypes yielded an average of 61% (39%–77% heterozygosity and 3.7 (2–6 alleles per locus. Population-level studies using the developed microsatellites will track the invasion front and monitor population-suppression dynamics. Additionally, cross-species amplification was detected in the invasive Ball, P. regius, and Northern African python, P. sebae. These markers can be used to address the hybridization potential of Burmese pythons and the larger, more aggressive P. sebae.

  2. Rapid microsatellite marker development using next generation pyrosequencing to inform invasive Burmese python -- Python molurus bivittatus -- management

    Science.gov (United States)

    Hunter, Margaret E.; Hart, Kristen M.

    2013-01-01

    Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus, is one of the most notable invasive species in the US, due to the threat it poses to imperiled species and the Greater Everglades ecosystem. To address population structure and relatedness, next generation sequencing was used to rapidly produce species-specific microsatellite loci. The Roche 454 GS-FLX Titanium platform provided 6616 di-, tri- and tetra-nucleotide repeats in 117,516 sequences. Using stringent criteria, 24 of 26 selected tri- and tetra-nucleotide loci were polymerase chain reaction (PCR) amplified and 18 were polymorphic. An additional six cross-species loci were amplified, and the resulting 24 loci were incorporated into eight PCR multiplexes. Multi-locus genotypes yielded an average of 61% (39%–77%) heterozygosity and 3.7 (2–6) alleles per locus. Population-level studies using the developed microsatellites will track the invasion front and monitor population-suppression dynamics. Additionally, cross-species amplification was detected in the invasive Ball, P. regius, and Northern African python, P. sebae. These markers can be used to address the hybridization potential of Burmese pythons and the larger, more aggressive P. sebae.

  3. 20 CFR 670.965 - What procedures apply to disclosure of information about Job Corps students and program activities?

    Science.gov (United States)

    2010-04-01

    ... information about Job Corps students and program activities? 670.965 Section 670.965 Employees' Benefits... INVESTMENT ACT Administrative and Management Provisions § 670.965 What procedures apply to disclosure of information about Job Corps students and program activities? (a) The Secretary develops procedures to respond...

  4. 28 CFR 5.210 - Amount of detail required in information relating to registrant's activities and expenditures.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Amount of detail required in information relating to registrant's activities and expenditures. 5.210 Section 5.210 Judicial Administration... § 5.210 Amount of detail required in information relating to registrant's activities and expenditures...

  5. EGFR induces expression of IRF-1 via STAT1 and STAT3 activation leading to growth arrest of human cancer cells

    DEFF Research Database (Denmark)

    Andersen, Peter; Pedersen, Mikkel Wandahl; Woetmann, Anders

    2008-01-01

    the constitutively active cancer specific receptor EGFRvIII are unable to mediate phosphorylation of these STATs and thereby incapable of inducing IRF-1. We also demonstrate that IRF-1 is expressed in an EGF dose-dependent manner, which correlates with inhibition of cell proliferation, and that the regulation of IRF......-1 is partially dependent on intracellular Src family kinase activity. Treatment with the dual specific Abl/c-Src kinase inhibitor AZD0530 significantly reduces the growth inhibitory effect of high EGF concentrations, signifying that EGFR induced IRF-1 is responsible for the observed growth...... products mediate growth arrest and activate immune effector cells, and which potentially could be involved in alerting the immune system in vivo leading to elimination of the transformed cells....

  6. Building and Leading the Next Generation of Exploration Launch Vehicles

    Science.gov (United States)

    Cook, Stephen A.; Vanhooser, Teresa

    2010-01-01

    NASA s Constellation Program is depending on the Ares Projects to deliver the crew and cargo launch capabilities needed to send human explorers to the Moon and beyond. Ares I and V will provide the core space launch capabilities needed to continue providing crew and cargo access to the International Space Station (ISS), and to build upon the U.S. history of human spaceflight to the Moon and beyond. Since 2005, Ares has made substantial progress on designing, developing, and testing the Ares I crew launch vehicle and has continued its in-depth studies of the Ares V cargo launch vehicle. In 2009, the Ares Projects plan to: conduct the first flight test of Ares I, test-fire the Ares I first stage solid rocket motor; build the first integrated Ares I upper stage; continue testing hardware for the J-2X upper stage engine, and continue refining the design of the Ares V cargo launch vehicle. These efforts come with serious challenges for the project leadership team as it continues to foster a culture of ownership and accountability, operate with limited funding, and works to maintain effective internal and external communications under intense external scrutiny.

  7. 78 FR 61366 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-10-03

    ... graduating, and the distribution of Nurse Anesthetists to practice in underserved, rural, or public health... or call (301) 443- 1984. SUPPLEMENTARY INFORMATION: Information Collection Request Title: Nurse... Services Administration (HRSA) provides advanced education nursing training grants to educational...

  8. 78 FR 56696 - Agency Information Collection Activities

    Science.gov (United States)

    2013-09-13

    ... COMMISSION Agency Information Collection Activities AGENCY: Equal Employment Opportunity Commission. ACTION... enabling a federal agency to determine whether recruitment activities are effectively reaching all segments... everyday activities such as interacting with others, thinking, preparing food, taking medications, or...

  9. 78 FR 11175 - Agency Information Collection Activities

    Science.gov (United States)

    2013-02-15

    ... COMMISSION Agency Information Collection Activities AGENCY: Equal Employment Opportunity Commission. ACTION... federal agency to determine whether recruitment activities are effectively reaching all segments of the... federal agencies only for evaluating whether an agency's recruitment activities are effectively reaching...

  10. Could low level laser therapy and highly active antiretroviral therapy lead to complete eradication of HIV-1 in vitro?

    CSIR Research Space (South Africa)

    Lugongolo, Masixole Y

    2017-01-01

    Full Text Available used to treat different medical conditions such as diabetic wounds, sports injuries and others. The technique involves exposure of cells or tissue to low levels of red and near infrared laser light. Both HIV infected and uninfected cells were laser...

  11. Enhancing Earth Science And IT Literacy Through Environmental Science Information Technology Activities

    Science.gov (United States)

    Cuff, K. E.; Molinaro, M.

    2004-12-01

    The Environmental Science Information Technology Activities (ESITA) program provides grades 9 and 10 students with under-represented minority backgrounds in the East San Francisco Bay Area with real-world opportunities to learn about and apply information technologies through a series of project-based activities related to environmental science. Supported by the NSF Information Technology Experiences for Students and Teachers (ITEST) program, ESITA activities engage students in the use of newly acquired information technology (IT) skills and understandings while performing air and water quality research investigations. One project that ESITA students have become involved in relates to the currently relevant issue of elevated levels of lead found in drinking waters in Washington, D.C. Students based in the Bay Area have initiated and maintained E-mail correspondence with children who attend elementary schools in the D.C. area. After receiving a thorough explanation of required sampling procedures devised by the Bay Area students, the elementary school children have sent 500 ml water samples from their homes and schools to Berkeley along with information about the locations from which the water samples were collected. These samples were then prepared for lead analysis at Lawrence Hall of Science by ESITA students, who used resulting data to perform a preliminary assessment of the geospatial distribution of lead trouble spots throughout Washington, DC. Later, ESITA student scientists will work with students from the UC Berkeley School of Public Health to develop surveys and questionnaires that generate high quality information useful with regard to assessing the impact of the current lead crisis on younger children in the Washington, D.C. area. Through the application of new understandings to current, real-world environmental problems and issues such as that related to lead, positive changes in students' attitudes towards IT and science have occurred, which accompany

  12. Activation of ethylene-responsive p-hydroxyphenylpyruvate dioxygenase leads to increased tocopherol levels during ripening in mango

    Science.gov (United States)

    Singh, Rajesh K.; Ali, Sharique A.; Nath, Pravendra; Sane, Vidhu A.

    2011-01-01

    Mango is characterized by high tocopherol and carotenoid content during ripening. From a cDNA screen of differentially expressing genes during mango ripening, a full-length p-hydroxyphenylpyruvate dioxygenase (MiHPPD) gene homologue was isolated that encodes a key enzyme in the biosynthesis of tocopherols. The gene encoded a 432-amino-acid protein. Transcript analysis during different stages of ripening revealed that the gene is ripening related and rapidly induced by ethylene. The increase in MiHPPD transcript accumulation was followed by an increase in tocopherol levels during ripening. The ripening-related increase in MiHPPD expression was also seen in response to abscisic acid and to alesser extent to indole-3-acetic acid. The expression of MiHPPD was not restricted to fruits but was also seen in other tissues such as leaves particularly during senescence. The strong ethylene induction of MiHPPD was also seen in young leaves indicating that ethylene induction of MiHPPD is tissue independent. Promoter analysis of MiHPPD gene in tomato discs and leaves of stable transgenic lines of Arabidopsis showed that the cis elements for ripening-related, ethylene-responsive, and senescence-related expression resided within the 1590 nt region upstream of the ATG codon. Functionality of the gene was demonstrated by the ability of the expressed protein in bacteria to convert p-hydroxyphenylpyruvate to homogentisate. These results provide the first evidence for HPPD expression during ripening of a climacteric fruit. PMID:21430290

  13. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis

    DEFF Research Database (Denmark)

    Rasmussen, Kasper D; Jia, Guangshuai; Johansen, Jens V

    2015-01-01

    DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to pro...... leukemic transformation by protecting enhancers from aberrant DNA methylation and that it is the combined silencing of several tumor suppressor genes in TET2 mutated hematopoietic cells that contributes to increased stem cell proliferation and leukemogenesis.......DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested...... to protect CG dinucleotide (CpG) islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO-induced AML. Using this model, we show that the primary effect of Tet...

  14. Lead-free BaTiO3 nanowires-based flexible nanocomposite generator

    Science.gov (United States)

    Park, Kwi-Il; Bae, Soo Bin; Yang, Seong Ho; Lee, Hyung Ik; Lee, Kisu; Lee, Seung Jun

    2014-07-01

    We have synthesized BaTiO3 nanowires (NWs) via a simple hydrothermal method at low temperature and developed a lead-free, flexible nanocomposite generator (NCG) device by a simple, low-cost, and scalable spin-coating method. The hydrothermally grown BaTiO3 NWs are mixed in a polymer matrix without a toxic dispersion enhancer to produce a piezoelectric nanocomposite (p-NC). During periodical and regular bending and unbending motions, the NCG device fabricated by utilizing a BaTiO3 NWs-polydimethylsiloxane (PDMS) composite successfully harvests the output voltage of ~7.0 V and current signals of ~360 nA, which are utilized to drive a liquid crystal display (LCD). We also characterized the instantaneous power (~1.2 μW) of the NCG device by calculating the load voltage and current through the connected external resistance.We have synthesized BaTiO3 nanowires (NWs) via a simple hydrothermal method at low temperature and developed a lead-free, flexible nanocomposite generator (NCG) device by a simple, low-cost, and scalable spin-coating method. The hydrothermally grown BaTiO3 NWs are mixed in a polymer matrix without a toxic dispersion enhancer to produce a piezoelectric nanocomposite (p-NC). During periodical and regular bending and unbending motions, the NCG device fabricated by utilizing a BaTiO3 NWs-polydimethylsiloxane (PDMS) composite successfully harvests the output voltage of ~7.0 V and current signals of ~360 nA, which are utilized to drive a liquid crystal display (LCD). We also characterized the instantaneous power (~1.2 μW) of the NCG device by calculating the load voltage and current through the connected external resistance. Electronic supplementary information (ESI) available: PDF materials involve the linear superposition test results (Fig. S1) and the durability test results (Fig. S2) of BaTiO3 NWs-based NCG device. A video file (Video S1) shows the power up of an LCD screen by the NCG device without any external energy source. See DOI: 10.1039/c4nr

  15. Information technologies for active and assisted living-Influences to the quality of life of an ageing society.

    Science.gov (United States)

    Siegel, Christian; Dorner, Thomas Ernst

    2017-04-01

    The current and upcoming demographic change in industrial countries is a challenge for our society, economically as well as socially. The aim of this article is to explore the influences of information and communication technologies applied to contribute to these trends and describe its impact to the quality of life and subjective health of elderly. In a structured literature review on (a) scientific publications and (b) outcome reports of ambient assisted living projects, we investigated these associations. The results are summarized according to the multidimensional approach of quality of life considering the bio-psycho-social model of health. The project outcomes of current initiatives are consolidated and recommendations for future research in the field of active and assisted living were issued. Current research efforts show that assistive information and communication technologies can successfully contribute to all dimensions of elderly's quality of life. As example technologies can empower them to control their health problems, compensate functional disabilities and increase their safety. Otherwise, remote-communication could lead to reduced face-to-face communication and social exclusion. More research using adequate methods: and instruments is needed to demonstrate the identified effects and to deliver evidence of the impact to the life of the heterogeneous population group of elderly. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Inflammation-induced brain endothelial activation leads to uptake of electrostatically stabilized iron oxide nanoparticles via sulfated glycosaminoglycans.

    Science.gov (United States)

    Berndt, Dominique; Millward, Jason M; Schnorr, Jörg; Taupitz, Matthias; Stangl, Verena; Paul, Friedemann; Wagner, Susanne; Wuerfel, Jens T; Sack, Ingolf; Ludwig, Antje; Infante-Duarte, Carmen

    2017-05-01

    Based on our previous data on the presence of very small superparamagnetic iron oxide nanoparticles (VSOP) on brain endothelial structures during experimental autoimmune encephalomyelitis (EAE), we investigated the mechanisms of VSOP binding on inflamed brain endothelial cells in vivo and in vitro. After intravenous application, VSOP were detected in brain endothelial cells of EAE animals at peak disease and prior to clinical onset. In vitro, inflammatory stimuli increased VSOP uptake by brain endothelial bEnd.3 cells, which we confirmed in primary endothelial cells and in bEnd.3 cells cultured under shear stress. Transmission electron microscopy and blocking experiments revealed that during inflammation VSOP were endocytosed by bEnd.3. Modified sulfated glycosaminoglycans (GAG) on inflamed brain endothelial cells were the primary binding site for VSOP, as GAG degradation and inhibition of GAG sulfation reduced VSOP uptake. Thus, VSOP-based MRI is sensitive to visualize early neuroinflammatory processes such as GAG modifications on brain endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Leveraging multi-generational workforce values in interactive information societies

    Directory of Open Access Journals (Sweden)

    Sophie van der Walt

    2010-08-01

    Full Text Available Background: The success of organisations relies on various factors including the ability of its multi-generational workforce to collaborate within the interactive information society. By developing an awareness of the different values of a diverse workforce, organisations may benefit from diversity. Various diversity factors, such as ethnicity, age and gender, impact on the way people interact, especially in the interactive information society.Objectives: This article advocates the need for generational awareness and addresses how this awareness presents benefits to companies, such as, increased productivity, improved succession planning policies and strategies to recruit and retain a diverse workforce. The research problem is directed at how diversity management influences Traditionalists, Baby Boomers, Generation X and Generation Y in terms of their work performance and co-worker relationships.Method: The research design combines Critical Theory and Generational Theory within the mixed-method paradigm. The sequential exploratory design was decided upon as it studies the unknown relationships between different generations of employees. The literature review was followed by a quantitative empirical research component and data was collected by means of a questionnaire. Results: The findings highlight specific differences between generations regarding their perspectives on work values and co-worker relationships, rewards, work-life balance and retirement.Conclusion: The article concludes with recommendations on the role diversity management plays in terms of work performance and co-worker relationships. By leveraging generational awareness in the interactive information society organizations with a multi-generational workforce will succeed in the competitive business environment.

  18. Time-dependent complete-active-space self-consistent-field method for atoms: Application to high-harmonic generation

    CERN Document Server

    Sato, Takeshi; Brezinova, Iva; Lackner, Fabian; Nagele, Stefan; Burgdorfer, Joachim

    2016-01-01

    We present the numerical implementation of the time-dependent complete-active-space self-consistent-field (TD-CASSCF) method [Phys. Rev. A, 88, 023402 (2013)] for atoms driven by a strong linearly polarized laser pulse. The present implementation treats the problem in its full dimensionality and introduces a gauge-invariant frozen-core approximation, an efficient evaluation of the Coulomb mean field scaling linearly with the number of basis functions, and a split-operator method specifically designed for stable propagation of stiff spatial derivative operators. We apply this method to high-harmonic generation in helium, beryllium, and neon and explore the role of electron correlations.

  19. 77 FR 50497 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-08-21

    ..., DC 20503. FOR FURTHER INFORMATION CONTACT: Norma Abdul-Malik, Environmental Protection Agency, 1200... address: abdul-malik.norma@epa.gov . SUPPLEMENTARY INFORMATION: EPA has submitted the following ICR to OMB...

  20. Improved side information generation for distributed video coding

    DEFF Research Database (Denmark)

    Huang, Xin; Forchhammer, Søren

    2008-01-01

    As a new coding paradigm, distributed video coding (DVC) deals with lossy source coding using side information to exploit the statistics at the decoder to reduce computational demands at the encoder. The performance of DVC highly depends on the quality of side information. With a better side...... information generation method, fewer bits will be requested from the encoder and more reliable decoded frames will be obtained. In this paper, a side information generation method is introduced to further improve the rate-distortion (RD) performance of transform domain distributed video coding. This algorithm...... consists of a variable block size based Y, U and V component motion estimation and an adaptive weighted overlapped block motion compensation (OBMC). The proposal is tested and compared with the results of an executable DVC codec released by DISCOVER group (DIStributed COding for Video sERvices). RD...

  1. Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

    LENUS (Irish Health Repository)

    Thewes, Verena

    2010-05-11

    Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

  2. Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

    2014-01-01

    Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake...... with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese...

  3. Neuronal gagging activity patterns may be generated by neurons in the reticular area dorsomedial to the retrofacial nucleus in dogs.

    Science.gov (United States)

    Fukuda, H; Koga, T

    1997-03-01

    Expulsion is induced when hypercapnea and hypoxia develop during retching, or when the oropharyngeal mucosa is irritated (the gag reflex). The central pattern generator (CPG) for expulsion has been suggested to coexist with the CPG for retching in the reticular area dorsomedial to the retrofacial nucleus, which may correspond to the Botzinger complex (BOT). However, its participation in gagging induced by oropharyngeal irritation is unclear. To elucidate such participation, the firing patterns of BOT neurons were observed during gagging induced by stimulation of superior laryngeal afferents in decerebrate, paralyzed dogs. Only 23% of inspiratory and 34% of expiratory BOT neurons increased their firing in response to stimulation of the superior laryngeal nerve. In contrast, 75% of nonrespiratory BOT neurons showed enhanced firing with this stimulation. During gagging, each nonrespiratory, inspiratory, and expiratory BOT neuron fired with the same pattern that they exhibited during expulsion caused by changes in blood gases. These firing patterns could be classified into five types and are thought to be appropriate for generating neuronal gagging activity. These results suggest that the CPG for expulsion in the BOT produces gagging when it is activated by oropharyngolaryngeal afferents.

  4. Formative research conducted in rural Appalachia to inform a community physical activity intervention.

    Science.gov (United States)

    Kruger, Tina M; Swanson, Mark; Davis, Rian E; Wright, Sherry; Dollarhide, Katie; Schoenberg, Nancy E

    2012-01-01

    Despite the well-established benefits of physical activity (PA), most Americans, especially those in rural, traditionally underserved areas, engage in considerably less PA than recommended. This study examines perceived barriers to and facilitators of PA and promising organized PA programs among rural Appalachians. Eight focus groups and seven group key informant interviews were conducted. This study was conducted in eastern Kentucky, in central Appalachia. One hundred and fourteen rural Appalachian residents (74% female, 91% white) participated. Open-ended, semistructured, and structured questions regarding perceptions of, barriers to/facilitators of, and examples of successful/failed PA programs were asked. Qualitative data analysis was conducted, including codebook development and steps taken to ensure rigor and transferability. Interrater reliability was over 94%. In addition to barriers that are consistent with those found in other populations, rural Appalachian residents indicated that travel time, family commitments, and inadequate community resources undermine PA. Suggested avenues to increase PA include partnership with churches and the U.S. Department of Agriculture's Cooperative Extension Service; programs that include families, are well advertised, and focus on health rather than appearance; and, underlying all suggestions, culturally relevant yet nonstereotyping activities. When developing PA interventions in rural Appalachia, it is important to employ community-based participatory approaches that leverage unique assets of the population and show potential in overcoming challenges to PA.

  5. Leveraging multi-generational workforce values in interactive information societies

    OpenAIRE

    Sophie van der Walt; Tanya du Plessis

    2010-01-01

    Background: The success of organisations relies on various factors including the ability of its multi-generational workforce to collaborate within the interactive information society. By developing an awareness of the different values of a diverse workforce, organisations may benefit from diversity. Various diversity factors, such as ethnicity, age and gender, impact on the way people interact, especially in the interactive information society.Objectives: This article advocates the need for g...

  6. 77 FR 60708 - Agency Information Collection Activities: Application To Adjust Status From Temporary to...

    Science.gov (United States)

    2012-10-04

    ... eRulemaking Portal Web site at http://www.Regulations.gov under e-Docket ID number USCIS-2008-0019... instructions, or additional information, please visit the Federal eRulemaking Portal site at: http://www... Portal at http://www.regulations.gov, and will include any personal information you provide. Therefore...

  7. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviors in aged mice.

    Science.gov (United States)

    Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B

    2017-06-01

    The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation, and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviors. Using both Grhl3-knockout mice (Grhl3(-/-) ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3(flox/flox) ), they performed histological expression analyses and behavioral tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety, and stress. They found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain; however, aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviors suggestive of decreased fear and anxiety. They conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behavior or hyperactivity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 775-788, 2017. © 2017 Wiley Periodicals, Inc.

  8. Deconstructing dementia and delirium hospital practice: using cultural historical activity theory to inform education approaches.

    Science.gov (United States)

    Teodorczuk, Andrew; Mukaetova-Ladinska, Elizabeta; Corbett, Sally; Welfare, Mark

    2015-08-01

    Older patients with dementia and delirium receive suboptimal hospital care. Policy calls for more effective education to address this though there is little consensus on what this entails. The purpose of this clarification study is to explore how practice gaps are constructed in relation to managing the confused hospitalised older patient. The intent is to inform educational processes in the work-place beyond traditional approaches such as training. Adopting grounded theory as a research method and working within a social constructionist paradigm we explored the practice gaps of 15 healthcare professionals by interview and conducted five focus groups with patients, carers and Liaison mental health professionals. Data were thematically analysed by constant comparison and theoretical sampling was undertaken until saturation reached. Categories were identified and pragmatic concepts developed grounded within the data. Findings were then further analysed using cultural historical activity theory as a deductive lens. Practice gaps in relation to managing the confused older patient are determined by factors operating at individual (knowledge and skill gaps, personal philosophy, task based practice), team (leadership, time and ward environmental factors) and organisational (power relationships, dominance of medical model, fragmentation of care services) levels. Conceptually, practice appeared to be influenced by socio-cultural ward factors and compounded by a failure to join up existing "patient" knowledge amongst professionals. Applying cultural historical activity theory to further illuminate the findings, the central object is defined as learning about the patient and the mediating artifacts are the care relationships. The overarching medical dominance emerges as an important cultural historical factor at play and staff rules and divisions of labour are exposed. Lastly key contradictions and tensions in the system that work against learning about the patient are

  9. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3 Leads to Increase of the Fatty Acid Biotransformation Activity.

    Directory of Open Access Journals (Sweden)

    Ji-Min Woo

    Full Text Available The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid-induced stress. The metabolic and genomic responses of E. coli BL21(DE3 and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3. Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3 expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1 into n-heptanoic acid (5 and 11-hydroxyundec-9-enoic acid (4. This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  10. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

    Science.gov (United States)

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  11. Aberrant glomerular filtration of urokinase-type plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    DEFF Research Database (Denmark)

    Staehr, Mette; Buhl, Kristian B; Andersen, René F

    2015-01-01

    ) induced nephrotic syndrome. Urine samples from 6 adult and 18 pediatric patients with nephrotic syndrome were analyzed for uPA activity and protein. PAN-treatment induced significant proteinuria in rats which coincided with increased urine uPA protein and activity, increased urine protease activity...... and total plasminogen/plasmin concentration and Na+ retention. Amiloride (2mg/kg/24h) concentration in urine was in the range 10-20 µmol/L and reduced significantly urine uPA activity, plasminogen activation, protease activity and sodium retention in PAN rats, while proteinuria was not altered. In paired...

  12. Survey of Neutron Generators for Active Interrogation

    Energy Technology Data Exchange (ETDEWEB)

    Moss, Calvin Elroy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Myers, William L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sundby, Gary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chichester, David L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Johnson, James P. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-05-02

    Some of these commercially available generators meet all of the requirements in Table 1, but there are other concerns. Most generators containing SF6 will be required to have the SF6 gas removed for shipping because of DOT regulations. However, Thermo Fisher has a DOT exemption. The P211 and B211 from Thermo Fisher meet the requirements listed in Table 1, but they are old designs and are no longer offered for sale. Also, they require 15 minutes or more of warmup before neutron output is available, and they lack a modern digital control. The nGen-300C from Starfire Industries is interesting because it is a portable system, but it uses the DD reaction for 2.5 MeV neutrons, which are not as penetrating as the 14 MeV neutrons from the DT reaction. The MP 320 from Thermo Fisher is another portable system, but the minimum pulse rate is 250 Hz, which is too fast for measurement of delayed neutrons and re-interrogation by delayed neutrons between pulses. The Genie 16 from Sodern (from France) probably meets the requirements, but the required power is probably too high for battery operation. The generators from Russia and China may be difficult to purchase, and service may not be available. The power required by some of these generators is low enough that batteries can be used. The portable units, nGen-300C and the MP320, could easily be operated with batteries. Other generators with low power requirements, as specified in the above vendors list, could possibly be operated with reason size batteries. The batteries do not need to be internal to the generator, but can be in a separate package. The availability of high capacity lithium batteries with sophisticated safety circuits makes battery operation more possible now than when lead acid batteries were used. The best path forward probably requires working with vendors of the existing systems. If Starfire Industries could be persuaded to put tritium in their nGen-300C generator, possibly in collaboration with a national

  13. Activation of protein kinase C delta following cerebral ischemia leads to release of cytochrome C from the mitochondria via bad pathway.

    Directory of Open Access Journals (Sweden)

    Kunjan R Dave

    Full Text Available The release of cytochrome c from the mitochondria following cerebral ischemia is a key event leading to cell death. The goal of the present study was to determine the mechanisms involved in post-ischemic activation of protein kinase c delta (δPKC that lead to cytochrome c release.We used a rat model of cardiac arrest as an in vivo model, and an in vitro analog, oxygen glucose deprivation (OGD in rat hippocampal synaptosomes. Cardiac arrest triggered translocation of δPKC to the mitochondrial fraction at 1 h reperfusion. In synaptosomes, the peptide inhibitor of δPKC blocked OGD-induced translocation to the mitochondria. We tested two potential pathways by which δPKC activation could lead to cytochrome c release: phosphorylation of phospholipid scramblase-3 (PLSCR3 and/or protein phosphatase 2A (PP2A. Cardiac arrest increased levels of phosphorlyated PLSCR3; however, inhibition of δPKC translocation failed to affect the OGD-induced increase in PLSCR3 in synaptosomal mitochondria suggesting the post-ischemic phosphorylation of PLSCR3 is not mediated by δPKC. Inhibition of either δPKC or PP2A decreased cytochrome c release from synaptosomal mitochondria. Cardiac arrest results in the dephosphorylation of Bad and Bax, both downstream targets of PP2A promoting apoptosis. Inhibition of δPKC or PP2A prevented OGD-induced Bad, but not Bax, dephosphorylation. To complement these studies, we used proteomics to identify novel mitochondrial substrates of δPKC.We conclude that δPKC initiates cytochrome c release via phosphorylation of PP2A and subsequent dephosphorylation of Bad and identified δPKC, PP2A and additional mitochondrial proteins as potential therapeutic targets for ischemic neuroprotection.

  14. 78 FR 20929 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-04-08

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... Resources and Services Administration (HRSA), Department of Health and Human Services (HHS). Operation of... section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35), the Health Resources...

  15. 77 FR 72870 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2012-12-06

    ... operations and care provision, and to generate efficiencies and economies of scale. Through this grant, HCCNs... goals such as quality improvement, data access and exchange, efficiency and effectiveness of network...

  16. Generation of optical coherent state superpositions for quantum information processing

    DEFF Research Database (Denmark)

    Tipsmark, Anders

    2012-01-01

    I dette projektarbejde med titlen “Generation of optical coherent state superpositions for quantum information processing” har målet været at generere optiske kat-tilstande. Dette er en kvantemekanisk superpositions tilstand af to koherente tilstande med stor amplitude. Sådan en tilstand er...

  17. Do newspapers lead with lead? A content analysis of how lead health risks to children are covered.

    Science.gov (United States)

    Brittle, Christine; Zint, Michaela

    2003-06-01

    Lead poses a serious environmental health risk to young children, causing such irreversible health effects as mental retardation, stunted growth, and hearing and visual impairment. Studies suggest that various sectors of the public, including children's caregivers, are not sufficiently concerned about this risk or knowledgeable about ways of minimizing it. Because newspapers are one of the primary ways members of the public learn about risks, the authors examined the characteristics and content of 152 newspaper articles on lead to determine when coverage occurred and what information was provided. Results revealed that newspapers most often covered lead as a local news story. Few articles identified children under six years of age as the most vulnerable group or provided important information on health effects, sources of exposure, or abatement methods. The authors' recommendations focus on helping environmental health professionals work with newspaper journalists to improve the information available to the public.

  18. A consultation with genetic information about obesity decreases self-blame about eating and leads to realistic weight loss goals in obese individuals.

    Science.gov (United States)

    Conradt, Matthias; Dierk, Jan-Michael; Schlumberger, Pia; Albohn, Christina; Rauh, Elisabeth; Hinney, Anke; Hebebrand, Johannes; Rief, Winfried

    2009-04-01

    This study tested the effects of a consultation using genetic information about obesity on attitudes relating to weight loss goals, self-blame about eating, and weight-related coping in obese individuals. Furthermore, the study sought to explore possible predictors for weight gain/loss. A total of 411 obese individuals were randomly assigned to two standardized consultations, with and without genetic information about obesity, and a control group without any intervention. After a 6-month follow-up, 253 obese individuals of the intervention groups and 98 individuals of the control group had a complete dataset. Data were analyzed regarding the independent variables assessment time, treatment group, and the familial predisposition (at least one obese parent or sibling). As dependent measures, attitudes about weight loss goals, weight-related self-blame, coping, and body shame were assessed via questionnaire or interview. Individuals with and without a familial predisposition profited in different ways from a consultation using genetic information about obesity: at follow-up, individuals with a familial predisposition reported mainly a relieving effect (less self-blame about eating). Both groups reported an adjustment to more realistic weight loss goals and a greater satisfaction with a 5% weight loss. Furthermore, the more negative obese individuals felt about their current weight at baseline, the higher the risk that these individuals had gained weight at follow-up. A consultation focusing on genetic factors might be helpful for obese individuals regardless of their familial predisposition, but only predisposed individuals showed a decrease in self-blame about eating. Negative thoughts and feelings about current weight might predict future weight gain.

  19. Epothilones as lead structures for new anticancer drugs--pharmacology, fermentation, and structure-activity-relationships.

    Science.gov (United States)

    Altmann, Karl-Heinz; Memmert, Klaus

    2008-01-01

    Epothilones (Epo's) A and B are naturally occurring microtubule-stabilizers, which inhibit the growth of human cancer cells in vitro at low nM or sub-nM concentrations. In contrast to taxol (paclitaxel, Taxol) epothilones are also active against different types of multidrug-resistant cancer cell lines in vitro and against multidrug-resistant tumors in vivo. Their attractive preclinical profile has made epothilones important lead structures in the search for improved cytotoxic anticancer drugs and Epo B (EPO906, patupilone) is currently undergoing Phase III clinical trials. Numerous synthetic and semisynthetic analogs have been prepared since the absolute stereochemistry of epothilones was first disclosed in mid-1996 and their in vitro biological activity has been determined. Apart from generating a wealth of SAR information, these efforts have led to the identification of at least six compounds (in addition to Epo B), which are currently at various stages of clinical evaluation in humans. The most advanced of these compounds, Epo B lactam BMS-247550 (ixabepilone), has recently obtained FDA approval for the treatment of metastatic and advanced breast cancer. This chapter will first provide a summary of the basic features of the biological profile of Epo B in vitro and in vivo. This will be followed by a review of the processes that have been developed for the fermentative production of Epo B. The main part of the chapter will focus on the most relevant aspects of the epothilone SAR with regard to effects on tubulin polymerization, in vitro antiproliferative activity, and in vivo antitumor activity. Particular emphasis will be placed on work conducted in the authors' own laboratories, but data from other groups will also be included. In a final section, the current status of those epothilone analogs undergoing clinical development will be briefly discussed.

  20. Introduction to information science

    CERN Document Server

    Bawden, David

    2012-01-01

    This landmark textbook takes a whole subject approach to Information Science as a discipline. Introduced by leading international scholars and offering a global perspective on the discipline, this is designed to be the standard text for students worldwide. The authors' expert narrative guides you through each of the essential building blocks of information science offering a concise introduction and expertly chosen further reading and resources.Critical topics covered include:foundations: concepts, theories and historical perspectivesorganising and retrieving Information information behaviour,

  1. Does contracting with owner operators lead to worse safety outcomes for US motor carriers? Evidence from the Motor Carrier Management Information System.

    Science.gov (United States)

    Monaco, Kristen; Redmon, Brydey

    2012-03-01

    Using data from the Motor Carrier Management Information System, we model crashes as a function of firm characteristics, with a focus on the employment relationship. We find that very small firms (one driver, one truck) and firms that contract with owner operators have fewer crashes than employee-only companies, once other firm characteristics and exposure are controlled. Additionally, though very small firms are more likely to have severe crashes, we find no relationship between the share of owner operators and crash severity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. 76 FR 81481 - Agency Information Collection Activities: Notice of Intent to Renew Collection, Large Trader Reports

    Science.gov (United States)

    2011-12-28

    ..., including through the use of appropriate electronic, mechanical, or other technological collection... provide the Commission with information to effectively conduct its market surveillance program, which...

  3. Prion proteins leading to neurodegeneration.

    Science.gov (United States)

    La Mendola, D; Mendola, D L; Pietropaolo, A; Pappalardo, G; Zannoni, C; Rizzarelli, E

    2008-12-01

    Prion diseases are fatal neurodegenerative disorders related to the conformational alteration of the prion protein (PrP C) into a pathogenic and protease-resistant isoform PrP(Sc). PrP(C) is a cell surface glycoprotein expressed mainly in the central nervous system and despite numerous efforts to elucidate its physiological role, the exact biological function remains unknown. Many lines of evidences indicate that prion is a copper binding protein and thus involved in the copper metabolism. Prion protein is not expressed only in mammals but also in other species such as birds, reptiles and fishes. However, it is noteworthy to point out that prion diseases are only observed in mammals while they seem to be spared to other species. The chicken prion protein (chPrP C) shares about 30% of identity in its primary sequence with mammal PrP C. Both types of proteins have an N-terminal domain endowed with tandem amino acid repeats (PHNPGY in the avian protein, PHGGGWQ in mammals), followed by a highly conserved hydrophobic core. Furthermore, NMR studies have highlighted a similar globular domain containing three alpha-helices, one short 3(10)-helix and a short antiparallel beta-sheet. Despite this structural similarity, it should be noted that the normal isoform of mammalian PrP C is totally degraded by proteinase K, while avian PrP C is not, thereby producing N-terminal domain peptide fragments stable to further proteolysis. Notably, the hexarepeat domain is considered essential for protein endocytosis, and it is supposed to be the analogous copper-binding octarepeat region of mammalian prion proteins. The number of copper binding sites, the affinity and the coordination environment of metal ions are still matter of discussion for both mammal and avian proteins. In this review, we summarize the similarities and the differences between mammalian and avian prion proteins, as revealed by studies carried out on the entire protein and related peptide fragments, using a range of

  4. LPS-activated monocytes are unresponsive to T4 phage and T4-generated Escherichia coli lysate

    Directory of Open Access Journals (Sweden)

    Katarzyna Bocian

    2016-08-01

    Full Text Available A growing body of data shows that bacteriophages can interact with different kinds of immune cells. The objective of this study was to investigate whether T4 bacteriophage and T4-generated Escherichia coli lysate affect functions of monocytes, the key population of immune cells involved in antibacterial immunity. To that end we evaluated how T4 and E. coli lysate influence the expression of main costimulatory molecules including CD40, CD80 and CD86, TLR2, TLR4 on monocytes, as well as the production of IL-6 and IL-12 in cultures of peripheral blood mononuclear cells (PBMCs. Separate experiments were performed on unactivated and LPS-activated PBMCs cultures. Both studied preparations significantly increased the percentage of CD14+CD16-CD40+ and CD14+CD16-CD80+ monocytes in unactivated PBMCs cultures, as well as the concentration of IL-6 and IL-12 in culture supernates. However, neither purified T4 nor E. coli lysate had any significant effect on monocytes in LPS-activated PBMCs cultures. We conclude that LPS-activated monocytes are unresponsive to phages and products of phage-induced lysis of bacteria. This study is highly relevant to phage therapy because it suggests that in patients with infections caused by Gram-negative bacteria the administration of phage preparations to patients and lysis of bacteria by phages are not likely to overly stimulate monocytes.

  5. Do Industries Lead the Stock Market? Gradual Diffusion of Information and Cross-Asset Return Predictability

    OpenAIRE

    Hong, Harrison; Torous, Walter; Valkanov, Rossen

    2002-01-01

    We test the hypothesis that the gradual diffusion of information across asset markets leads to cross-asset return predictability. Using thirty-four industry portfolios and the broad market index as our test assets, we establish several key results. First, a number of industries such as retail, services, commercial real estate, metal, and petroleum lead the stock market by up to two months. In contrast, the market, which is widely followed, only leads a few industries. Importantly, an industry...

  6. 75 FR 81650 - Agency Information Collection Activities:

    Science.gov (United States)

    2010-12-28

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms, and Explosives Agency Information Collection Activities: Proposed Collection; Comments Requested ACTION: 30-Day Notice of Information Collection Under Review: Open Letter to...

  7. Pattern Recognition-Assisted Infrared Library Searching of the Paint Data Query Database to Enhance Lead Information from Automotive Paint Trace Evidence.

    Science.gov (United States)

    Lavine, Barry K; White, Collin G; Allen, Matthew D; Weakley, Andrew

    2017-03-01

    Multilayered automotive paint fragments, which are one of the most complex materials encountered in the forensic science laboratory, provide crucial links in criminal investigations and prosecutions. To determine the origin of these paint fragments, forensic automotive paint examiners have turned to the paint data query (PDQ) database, which allows the forensic examiner to compare the layer sequence and color, texture, and composition of the sample to paint systems of the original equipment manufacturer (OEM). However, modern automotive paints have a thin color coat and this layer on a microscopic fragment is often too thin to obtain accurate chemical and topcoat color information. A search engine has been developed for the infrared (IR) spectral libraries of the PDQ database in an effort to improve discrimination capability and permit quantification of discrimination power for OEM automotive paint comparisons. The similarity of IR spectra of the corresponding layers of various records for original finishes in the PDQ database often results in poor discrimination using commercial library search algorithms. A pattern recognition approach employing pre-filters and a cross-correlation library search algorithm that performs both a forward and backward search has been used to significantly improve the discrimination of IR spectra in the PDQ database and thus improve the accuracy of the search. This improvement permits inter-comparison of OEM automotive paint layer systems using the IR spectra alone. Such information can serve to quantify the discrimination power of the original automotive paint encountered in casework and further efforts to succinctly communicate trace evidence to the courts.

  8. Lead-cooled system design and challenges in the frame of Generation IV International Forum

    Science.gov (United States)

    Cinotti, Luciano; Smith, Craig F.; Sekimoto, Hiroshi; Mansani, Luigi; Reale, Marco; Sienicki, James J.

    2011-08-01

    The Generation IV International Forum (GIF) Technology Roadmap identified the Lead-cooled Fast Reactor (LFR) as a technology well suited for electricity generation, hydrogen production and actinide management in a closed fuel cycle. One of the most important features of the LFR is the fact that lead is a relatively inert coolant, a feature that conveys significant advantages in terms of safety, system simplification, and the consequent potential for economic performance. In 2004, the GIF LFR Provisional System Steering Committee was organized and began to develop the LFR System Research Plan. The committee selected two pool-type reactor concepts as candidates for international cooperation and joint development in the GIF framework: these are the Small Secure Transportable Autonomous Reactor (SSTAR); and the European Lead-cooled System (ELSY). The high boiling point (1745 °C) of lead has a beneficial impact to the safety of the system, whereas its high melting point (327.4 °C) requires new engineering strategies, especially for In-Service-Inspection and refuelling. Lead, especially at high temperatures, is also relatively corrosive towards structural materials. This necessitates that coolant purity and the level of dissolved oxygen be carefully controlled, in addition to the proper selection of structural materials. For the GIF LFR concepts, lead has been chosen as the coolant rather than Lead-Bismuth Eutectic primarily because of its greatly reduced generation of the alpha-emitting 210Po isotope formed in the coolant. This results in significantly reduced levels of radioactive contamination of the coolant while minimizing the effect of decay power in the coolant from such contaminants; an additional consideration is the desire to eliminate dependence on bismuth which might be a limited resource. This paper provides an overview of the historical development of the LFR, a summary of the advantages and challenges associated with heavy liquid metal coolants, and an

  9. Extraction of lead from waste CRT funnel glass by generating lead sulfide - An approach for electronic waste management.

    Science.gov (United States)

    Hu, Biao; Hui, Wenlong

    2017-09-01

    Waste cathode ray tube (CRT) funnel glass is the key and difficult points in waste electrical and electronic equipment (WEEE) disposal. In this paper, a novel and effective process for the detoxification and reutilization of waste CRT funnel glass was developed by generating lead sulfide precipitate via a high-temperature melting process. The central function in this process was the generation of lead sulfide, which gathered at the bottom of the crucible and was then separated from the slag. Sodium carbonate was used as a flux and reaction agent, and sodium sulfide was used as a precipitating agent. The experimental results revealed that the lead sulfide recovery rate initially increased with an increase in the amount of added sodium carbonate, the amount of sodium sulfide, the temperature, and the holding time and then reached an equilibrium value. The maximum lead sulfide recovery rate was approximately 93%, at the optimum sodium carbonate level, sodium sulfide level, temperature, and holding time of 25%, 8%, 1200°C, and 2h, respectively. The glass slag can be made into sodium and potassium silicate by hydrolysis in an environmental and economical process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Automated Narratives and Journalistic Text Generation: The Lead Organization Structure Translated into Code.

    Directory of Open Access Journals (Sweden)

    Márcio Carneiro dos Santos

    2016-07-01

    Full Text Available It describes the experiment of building a software capable of generating leads and newspaper titles in an automated fashion from information obtained from the Internet. The theoretical possibility Lage already provided by the end of last century is based on relatively rigid and simple structure of this type of story construction, which facilitates the representation or translation of its syntax in terms of instructions that the computer can execute. The paper also discusses the relationship between society, technique and technology, making a brief history of the introduction of digital solutions in newsrooms and their impacts. The development was done with the Python programming language and NLTK- Natural Language Toolkit library - and used the results of the Brazilian Soccer Championship 2013 published on an internet portal as a data source.

  11. Neural evidence that vivid imagining can lead to false remembering.

    Science.gov (United States)

    Gonsalves, Brian; Reber, Paul J; Gitelman, Darren R; Parrish, Todd B; Mesulam, M-Marsel; Paller, Ken A

    2004-10-01

    The imperfect nature of memory is highlighted by the regularity with which people fail to remember, or worse, remember something that never happened. We investigated the formation of a particular type of erroneous memory by monitoring brain activity using functional magnetic resonance imaging during the presentation of words and photos. Participants generated a visual image of a common object in response to each word. Subsequently, they sometimes claimed to have seen photos of specific objects they had imagined but not actually seen. In precuneus and inferior parietal regions of the cerebral cortex, activations in response to words were greater when participants subsequently claimed to have seen the corresponding object than when a false memory for that object was not subsequently produced. These findings indicate that brain activity reflecting the engagement of visual imagery can lead to falsely remembering something that was only imagined.

  12. Do personally-tailored videos in a web-based physical activity intervention lead to higher attention and recall? – An eye-tracking study.

    Directory of Open Access Journals (Sweden)

    Stephanie eAlley

    2014-02-01

    Full Text Available Over half of the Australian population does not meet physical activity guidelines and has an increased risk of chronic disease. Web-based physical activity interventions have the potential to reach large numbers of the population at low cost, however issues have been identified with usage and participant retention. Personalised (computer-tailored physical activity advice delivered through video has the potential to address low engagement, however it is unclear whether it is more effective in engaging participants when compared to text-delivered personalised advice. This study compared the attention and recall outcomes of tailored physical activity advice in video- versus text-format. Participants (n=41 were randomly assigned to receive either video- or text-tailored feedback with identical content. Outcome measures included attention to the feedback, measured through advanced eye-tracking technology (Tobii 120, and recall of the advice, measured through a post intervention interview. Between group ANOVA’s, Mann-Whitney U tests and Chi square analyses were applied. Participants in the video-group displayed greater attention to the physical activity feedback in terms of gaze-duration on the feedback (7.7 min vs. 3.6 min, p< 001, total fixation-duration on the feedback (6.0 min vs. 3.3 min, p< 001, and focusing on feedback (6.8 vs. 3.5 min, p< 001. Despite both groups having the same ability to navigate through the feedback, the video-group completed a significantly (p< .001 higher percentage of feedback sections (95% compared to the text-group (66%. The main messages were recalled in both groups, but many details were forgotten. No significant between group differences were found for message recall. These results suggest that video-tailored feedback leads to greater attention compared to text-tailored feedback. More research is needed to determine how message recall can be improved, and whether video-tailored advice can lead to greater health

  13. Can the London 2012 Olympics 'inspire a generation' to do more physical or sporting activities? An overview of systematic reviews.

    Science.gov (United States)

    Mahtani, Kamal Ram; Protheroe, Joanne; Slight, Sarah Patricia; Demarzo, Marcelo Marcos Piva; Blakeman, Thomas; Barton, Christopher A; Brijnath, Bianca; Roberts, Nia

    2013-01-07

    To examine if there is an increased participation in physical or sporting activities following an Olympic or Paralympic games. Overview of systematic reviews. We searched the Medline, Embase, Cochrane, DARE, SportDISCUS and Web of Knowledge databases. In addition, we searched for 'grey literature' in Google, Google scholar and on the International Olympic Committee websites. We restricted our search to those reviews published in English. We used the AMSTAR tool to assess the methodological quality of those systematic reviews included. The primary outcome was evidence for an increased participation in physical or sporting activities. Secondary outcomes included public perceptions of sport during and after an Olympic games, barriers to increased sports participation and any other non-sporting health benefits. Our systematic search revealed 844 citations, of which only two matched our inclusion criteria. The quality of these two reviews was assessed by three independent reviewers as 'good' using the AMSTAR tool for quality appraisal. Both reviews reported little evidence of an increased uptake of sporting activity following an Olympic Games event. Other effects on health, for example, changes in hospital admissions, suicide rates and drug use, were cited although there was insufficient evidence to see an overall effect. There is a paucity of evidence to support the notion that hosting an Olympic games leads to an increased participation in physical or sporting activities for host countries. We also found little evidence to suggest other health benefits. We conclude that the true success of these and future games should be evaluated by high-quality, evidence-based studies that have been commissioned before, during and following the completion of the event. Only then can the true success and legacy of the games be established.

  14. 76 FR 44400 - Proposed Information Collection (Certificate as to Assets) Activity: Comment Request

    Science.gov (United States)

    2011-07-25

    ... Benefits Administration (VBA), Department of Veterans Affairs (VA), is announcing an opportunity for public... pursuant to Section 3506(c)(2)(A) of the PRA. With respect to the following collection of information, VBA... performance of VBA's functions, including whether the information will have practical utility; (2) the...

  15. 78 FR 67394 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Exhibit B to...

    Science.gov (United States)

    2013-11-12

    ... Division (NSD), will be submitting the following information collection request to the Office of Management... collection of information are encouraged. Comments should address one or more of the following four points... Justice. Pursuant to Section 212 of Public Law 110-81, the Honest Leadership and Open Government Act of...

  16. 78 FR 41829 - Pipeline Safety: Information Collection Activities, Revision to Annual Report for Hazardous...

    Science.gov (United States)

    2013-07-11

    ... Information Collection Request abstracted below is being forwarded to the Office of Management and Budget (OMB...: Fax: 1-202-395-5806. Mail: Office of Information and Regulatory Affairs (OIRA), Records Management... Institute (API) Association of Oil Pipelines (AOPL) This 30-day notice responds to the comments, which may...

  17. 77 FR 58869 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Application To...

    Science.gov (United States)

    2012-09-24

    ... Firearms Act (NFA) Firearms ACTION: 60-Day Notice of Information Collection Under Review. The Department of... Temporarily Export Certain National Firearms Act (NFA) Firearms. (3) Agency form number, if any, and the... The information is used by ATF to determine the lawful transportation of an NFA firearm and/or to...

  18. Does CPAP lead to change in BMI?

    Science.gov (United States)

    Redenius, Rachel; Murphy, Carli; O'Neill, Erin; Al-Hamwi, Majed; Zallek, Sarah Nath

    2008-06-15

    Obesity is an important risk factor for obstructive sleep apnea syndrome (OSAS), and weight loss can reduce apnea severity or even lead to resolution in some patients. Effective CPAP therapy may lead to weight loss by any of several proposed mechanisms, including, but not limited to, increased physical activity and increased responsiveness to leptin. This retrospective study sought to determine whether subjects who adhered to prescribed CPAP treatment for OSAS would lose weight, or gain less weight than control subjects who were either untreated or did not adhere to prescribed CPAP treatment. BMI was determined at the time of diagnosis and at followup approximately 1 year (10-14 months) later. Subjects who used CPAP > or = 4 h per night and > or = 70% of nights were considered treatment subjects. Control subjects used no treatment for OSAS or used CPAP weight gain in some; none lost weight. CPAP may affect weight in ways not measured here. Physicians should stress an active weight loss plan and not assume CPAP alone will lead to weight loss. A larger, prospective study may help clarify these findings.

  19. A method for integrating occupational indoor air quality with building information modeling for scheduling construction activities

    National Research Council Canada - National Science Library

    Altaf, Mohammed Sadiq; Hashisho, Zaher; Hussein, Mohamed Al

    2014-01-01

    ...’ health as construction activities frequently generate airborne pollutants. This paper presents a methodology to predict the concentration of air pollutants during construction activities using building information modeling (BIM...

  20. 76 FR 58265 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-09-20

    ... single process or group of processes used to adjust and improve the physical and aesthetic... have subsequently changed; train personnel to be able to respond to a collection of information; search...

  1. Development in fiscal 1999 of technologies to put photovoltaic power generation systems into practical use. International cooperation projects (Collection of information on IEA photovoltaic power generation program); 1999 nendo taiyoko hatsuden system jitsuyoka gijutsu kaihatsu seika hokokusho. Kokusai kyoryoku jigyo (IEA taiyoko hatsuden program ni kansuru joho shushu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    Items of information were collected on development of technologies to put photovoltaic power generation systems into practical use, the international cooperation projects, and the IEA photovoltaic power generation program. This paper summarizes the achievements in fiscal 1999. In the activities of IEA/REWP/PVPS in the current fiscal year, the 13th and 14th Executive Committee meetings, and the 3rd Executive Conference were held. The Task 1 has performed such activities as ISR, NSR, Newsletters, and opening the Internet homepage. The Task 2 activities included structuring about 260 databases for the operation characteristics of photovoltaic power generation systems, and completing the internal material handbooks on measurement and monitoring. A new work plan was prepared for the Task 3 regarding an independent photovoltaic power generation plant for use in an island. For the building integrated photovoltaic power generation system in the Task 7, survey activities were executed by utilizing expertise conferences on building designs, system technologies, and non-technical impediments. In the feasibility survey and research on large-scale photovoltaic power generation utilizing unused land such as desert for the Task 8, the programs were established. (NEDO)

  2. New orally active DNA minor groove binding small molecule CT-1 acts against breast cancer by targeting tumor DNA damage leading to p53-dependent apoptosis.

    Science.gov (United States)

    Saini, Karan Singh; Hamidullah; Ashraf, Raghib; Mandalapu, Dhanaraju; Das, Sharmistha; Siddiqui, Mohd Quadir; Dwivedi, Sonam; Sarkar, Jayanta; Sharma, Vishnu Lal; Konwar, Rituraj

    2017-04-01

    Targeting tumor DNA damage and p53 pathway is a clinically established strategy in the development of cancer chemotherapeutics. Majority of anti-cancer drugs are delivered through parenteral route for reasons like severe toxicity, lack of stability, and poor enteral absorption. Current DNA targeting drugs in clinical like anthracycline suffers from major drawbacks like cardiotoxicity. Here, we report identification of a new orally active small molecule curcumin-triazole conjugate (CT-1) with significant anti-breast cancer activity in vitro and in vivo. CT-1 selectively and significantly inhibits viability of breast cancer cell lines; retards cells cycle progression at S phase and induce mitochondrial-mediated cell apoptosis. CT-1 selectively binds to minor groove of DNA and induces DNA damage leading to increase in p53 along with decrease in its ubiquitination. Inhibition of p53 with pharmacological inhibitor as well as siRNA revealed the necessity of p53 in CT-1-mediated anti-cancer effects in breast cancer cells. Studies using several other intact p53 and deficient p53 cancer cell lines further confirmed necessity of p53 in CT-1-mediated anti-cancer response. Pharmacological inhibition of pan-caspase showed CT-1 induces caspase-dependent cell death in breast cancer cells. Most interestingly, oral administration of CT-1 induces significant inhibition of tumor growth in LA-7 syngeneic orthotropic rat mammary tumor model. CT-1 treated mammary tumor shows enhancement in DNA damage, p53 upregulation, and apoptosis. Collectively, CT-1 exhibits potent anti-cancer effect both in vitro and in vivo and could serve as a safe orally active lead for anti-cancer drug development. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Ingestion of the anti-bacterial agent, gemifloxacin mesylate, leads to increased gst activity and peroxidation products in hemolymph of Galleria mellonella l. (lepidoptera: pyralidae).

    Science.gov (United States)

    Erdem, Meltem; Küçük, Ceyhun; Büyükgüzel, Ender; Büyükgüzel, Kemal

    2016-12-01

    Gemifloxacin mesylate (GEM) is a synthetic, fourth-generation fluoroquinolone antibacterial antibiotic that has a broad spectrum of activity against bacteria. GEM inhibits DNA synthesis by inhibiting DNA gyrase and topoisomerase IV activities. Recent research into insect nutrition and mass-rearing programs, in which antibiotics are incorporated into the culture media to maintain diet quality, raised a question of whether clinical antibiotics influence the health or biological performance of the insects that ingest these compounds. Because some antibiotics are pro-oxidant compounds, we addressed the question with experiments designed to assess the effects of GEM (mesylate salt) on oxidative stress indicators, using Galleria mellonella larvae. The insects were reared from first-instar larvae to adulthood on artificial diets amended with GEM at 0.001, 0.01, 0.1, or 1.0%. Feeding on the 1% diets led to significantly increased hemolymph contents of the lipid peroxidation product, malondialdehyde and protein oxidation products, protein carbonyl. All GEM concentrations led to increased hemolymph glutathione S-transferase activity. We inferred that although it was not directly lethal to G. mellonella larvae, dietary exposure to GEM exerts measurable oxidative damage, possibly on insects generally. Long-term, multigenerational effects remain unknown. © 2016 Wiley Periodicals, Inc.

  4. Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.

    Science.gov (United States)

    Tonkin, Daniel R; Whitmore, Alan; Johnston, Robert E; Barro, Mario

    2012-06-22

    Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity. Published by Elsevier Ltd.

  5. 77 FR 24701 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-04-25

    ..., 725 17th Street NW., Washington, DC 20503. FOR FURTHER INFORMATION CONTACT: Matthew Reed, Drinking...: reed[email protected] . SUPPLEMENTARY INFORMATION: EPA has submitted the following ICR to OMB for review..., Director, Collection Strategies Division. BILLING CODE 6560-50-P ...

  6. 76 FR 27080 - Agency Information Collection Activities: Application To Pay Off or Discharge an Alien Crewman

    Science.gov (United States)

    2011-05-10

    ... Off or Discharge an Alien Crewman AGENCY: U.S. Customs and Border Protection, Department of Homeland... Discharge an Alien Crewman (Form I-408). This is a proposed extension of an information collection that was... techniques or other forms of information. Title: Application To Pay Off or Discharge an Alien Crewman. OMB...

  7. 76 FR 33275 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-06-08

    ... material, Confidential Business Information (CBI), or other information whose public disclosure is... December 23, 1971, and amended on December 14, 1988, October 17, 2000, and September 9, 2010. Particulate... reasonably be anticipated to endanger public health or welfare. The control of emissions of particulate...

  8. 78 FR 53162 - Agency Information Collection Activities: Submission to OMB for Reinstatement, Without Change, of...

    Science.gov (United States)

    2013-08-28

    ... a Previously Approved Collection; Comment Request AGENCY: National Credit Union Administration (NCUA.... This collection of information is necessary to protect the National Credit Union Share Insurance Fund.... The collection of information requirement is for those federally insured state-chartered credit unions...

  9. Classification Active Learning Based on Mutual Information

    Directory of Open Access Journals (Sweden)

    Jamshid Sourati

    2016-02-01

    Full Text Available Selecting a subset of samples to label from a large pool of unlabeled data points, such that a sufficiently accurate classifier is obtained using a reasonably small training set is a challenging, yet critical problem. Challenging, since solving this problem includes cumbersome combinatorial computations, and critical, due to the fact that labeling is an expensive and time-consuming task, hence we always aim to minimize the number of required labels. While information theoretical objectives, such as mutual information (MI between the labels, have been successfully used in sequential querying, it is not straightforward to generalize these objectives to batch mode. This is because evaluation and optimization of functions which are trivial in individual querying settings become intractable for many objectives when we are to select multiple queries. In this paper, we develop a framework, where we propose efficient ways of evaluating and maximizing the MI between labels as an objective for batch mode active learning. Our proposed framework efficiently reduces the computational complexity from an order proportional to the batch size, when no approximation is applied, to the linear cost. The performance of this framework is evaluated using data sets from several fields showing that the proposed framework leads to efficient active learning for most of the data sets.

  10. Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative/nitrosative stress in human bronchial epithelial cell line.

    Science.gov (United States)

    Profita, Mirella; Albano, Giusy Daniela; Montalbano, Angela Marina; Di Sano, Caterina; Anzalone, Giulia; Gagliardo, Rosalia; Riccobono, Loredana; Bonanno, Anna; Siena, Liboria; Pieper, Michael Paul; Gjomarkaj, Mark

    2013-12-01

    The induction of nitric oxide synthase (iNOS) expression via the signal transducer and activator of transcription 1 (STAT-1) is involved in the mechanism of oxidative/nitrosative stress. We investigated whether acetylcholine (ACh) generates oxidative/nitrosative stress in bronchial epithelial cells during airway inflammation of COPD and evaluated the effects of Tiotropium, a once-daily antimuscarinic drug, and Olodaterol, a long-acting β2-agonist on these mechanisms. Human bronchial epithelial cells (16-HBE) were stimulated (4h, 37°C) with induced sputum supernatants (ISSs) from healthy controls (HC) (n=10), healthy smokers (HS) (n=10) or COPD patients (n=10), as well as with ACh (from 1μM to 100μM). The activation of STAT-1 pathway (STAT-1Ser727 and STAT-1Tyr701) and iNOS was evaluated in the cell lysates by Western blot analysis as well as nitrotyrosine levels by ELISA, while reactive oxygen species (ROS) were evaluated by flow cytometry. Finally, the effect of Tiotropium (Spiriva®) (100nM), alone or in combination with Olodaterol (1nM), was tested in this model. ISSs from COPD patients significantly increased the phosphorylation of STAT-1Ser727 and STAT-1Tyr701, iNOS and ROS/Nitrotyrosine when compared with ISSs from HC or HS subjects in 16-HBE cells. Furthermore, synthetic ACh increased all these parameters in stimulated 16HBE when compared with untreated cells. Tiotropium and Olodaterol reduced the oxidative/nitrosative stress generated by ACh and ISSs. We concluded that ACh mediated the oxidative/nitrosative stress involving the STAT-1 pathway activation in human bronchial epithelial cells during COPD. β2-Long acting and antimuscarinic drugs, normally used in the treatment of COPD as bronchodilator, might be able to control these cellular events. © 2013 Elsevier B.V. All rights reserved.

  11. [Can nitrates lead to indirect toxicity?].

    Science.gov (United States)

    Hamon, M

    2007-09-01

    For many years, nitrates have been used, at low dosages, as an additive in salted food. New laws have been promulgated to limit their concentration in water due to increased levels found in soils, rivers and even the aquifer. Although nitrate ions themselves have not toxic properties, bacterial reduction into nitrite ions (occurring even in aqueous medium) can lead to nitrous anhydride, which in turn generates nitrosonium ions. Nitrosium ions react with secondary amine to give nitrosamines, many of which are cancer-inducing agents at very low doses. Opinions on this toxicity are clear-cut and difficult to reconcile. In fact, increased levels are due, in a large part, to the use of nitrates as fertiliéers but also to bacterial transformation of human and animal nitrogenous wastes such as urea.

  12. Who Gets to Lead the Multinational Team?

    DEFF Research Database (Denmark)

    Paunova, Minna

    2017-01-01

    of their core self-evaluations. A study of over 230 individuals from 46 nationalities working in 36 self-managing teams generally supports the expected main and moderation effects. Individual core self-evaluations enhance an otherwise weak effect of English proficiency, but compensate for low levels of national......This article examines the emergence of informal leadership in multinational teams. Building on and extending status characteristics theory, the article proposes and tests a model that describes how global inequalities reproduce in multinational teams, and accounts for who gets to lead these teams...

  13. 78 FR 2274 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-01-10

    ..., or provide the information requested. This includes the time needed to review instructions, to... estimate of burden is as follows: Number of Responses per Total Hours per Total burden Form name...

  14. INFORMATION AND COMMUNICATION PEDAGOGICAL ENVIRONMENT AS MEANS OF FORMING OF MOTIVATION TO PROFESSIONAL ACTIVITY OF PRIMARY SCHOOL TEACHERS

    Directory of Open Access Journals (Sweden)

    I.V. Onishchenko

    2014-04-01

    Full Text Available In terms of education informatization the formation of motivation to professional activity of the future primary school teacher most effectively takes place in information and communication pedagogical environment that provides new ways of presenting information, promotes the development of needs and readiness of students to perform professional activities with application of information and communication technologies. Information and communication pedagogical environment is a complex, multi-element pedagogical system, which accumulates information, organizational, intellectual, methodological, technical, program resources and promotes information and educational interaction in the model «teacher – student – environment». This environment creates favorable terms for forming of the expressed interest in the profession of primary school teacher, motivational-valued attitude toward pedagogical activity, promotes the education of students in information and pedagogical culture and creative activity in the independent capture of professional disciplines. Forming of interest in the profession of primary school teacher is assisted by bringing in of future specialist to the creative searches by the decision of the research tasks, creative nature, creation of own electronic products, creative projects. Information and communication pedagogical environment provides the realization of the potential of students by bringing them to self-education, which in terms of the environment acquires creative and research direction and promotes for non-standard decision of professional tasks on innovative bases.

  15. Next-to-leading order corrections to the valon model

    Indian Academy of Sciences (India)

    A seminumerical solution to the valon model at next-to-leading order (NLO) in the Laguerre polynomials is presented. We used the valon model to generate the structure of proton with respect to the Laguerre polynomials method. The results are compared with H1 data and other parametrizations.

  16. Soil bacterial flora and enzymatic activities in zinc and lead ...

    African Journals Online (AJOL)

    JTEkanem

    Abstract. Soil bacterial flora and enzymatic activities in lead and zinc contaminated soil of Ishiagu, ... concentration. This showed that the higher the heavy metal concentration the lower the enzymatic activities. Urease, dehydrogenase activity, hydrogen peroxidase and polyphenol ..... high concentrations and even inhibit the.

  17. 78 FR 59360 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-09-26

    ... and HIV Prevention Program. The evaluation is designed to determine best practices and gender... participating in the program and their parents will be affected by this data collection. Need and Proposed Use... this context means the time expended by persons to generate, maintain, retain, disclose or provide the...

  18. Enhanced Catalysis Activity in a Coordinatively Unsaturated Cobalt-MOF Generated via Single-Crystal-to-Single-Crystal Dehydration.

    Science.gov (United States)

    Ren, Hai-Yun; Yao, Ru-Xin; Zhang, Xian-Ming

    2015-07-06

    Hydrothermal reaction of Co(NO3)2 and terphenyl-3,2",5",3'-tetracarboxyate (H4tpta) generated Co3(OH)2 chains based 3D coordination framework Co3(OH)2(tpta)(H2O)4 (1) that suffered from single-crystal-to-single-crystal dehydration by heating at 160 °C and was transformed into dehydrated Co3(OH)2(tpta) (1a). During the dehydration course, the local coordination environment of part of the Co atoms was transformed from saturated octahedron to coordinatively unsaturated tetrahedron. Heterogenous catalytic experiments on allylic oxidation of cyclohexene show that dehydrated 1a has 6 times enhanced catalytic activity than as-synthesized 1 by using tert-butyl hydroperoxide (t-BuOOH) as oxidant. The activation energy for the oxidation of cylcohexene with 1a catalyst was 67.3 kJ/mol, far below the value with 1 catalysts, which clearly suggested that coordinatively unsaturated Co(II) sites in 1a have played a significant role in decreasing the activation energy. It is interestingly found that heterogeneous catalytic oxidation of cyclohexene in 1a not only gives the higher conversion of 73.6% but also shows very high selectivity toward 2-cyclohexene-1-one (ca. 64.9%), as evidenced in high turnover numbers (ca. 161) based on the open Co(II) sites of 1a catalyst. Further experiments with a radical trap indicate a radical chain mechanism. This work demonstrates that creativity of coordinatively unsaturated metal sites in MOFs could significantly enhance heterogeneous catalytic activity and selectivity.

  19. Ion imprinted activated carbon solid-phase extraction coupled to flame atomic absorption spectrometry for selective determination of lead ions in environmental samples

    Energy Technology Data Exchange (ETDEWEB)

    Naraghi, Kiyana; Panahi, Homayon Ahmad; Hassani, Amir Hesam [Islamic Azad University, Tehran (Korea, Republic of); Moniri, Elham [Islamic Azad University, Varamin (Iran, Islamic Republic of)

    2014-10-15

    A simple lead ion imprinted sorbent was synthesized by coupling activated carbon with a known metal chelating compound, iminodiacetic acid. The ion imprinted sorbent has been characterized using Fourier transform infrared spectroscopy, elemental analysis and thermogravimetric analysis and subjected for the extraction and determination of trace Pb(II) in environmental water samples. The optimum pH value for sorption of the lead ion was 6.5. The sorption capacity of lead imprinted sorbent was 42.2 mg g{sup −1}. The chelating imprinted sorbent can be reused for five cycles of sorption-desorption without any significant change in sorption capacity. Compared with non-imprinted polymer particles, the lead ion imprinted sorbent showed high adsorption capacity, significant selectivity, good site accessibility for Pb(II). The equilibrium adsorption data of Pb(II) by modified resin were analyzed by Langmuir, Freundlich, Temkin and Redlich-Peterson models.

  20. Meetings: From the transmission of information to the sharing of actionable knowledge

    DEFF Research Database (Denmark)

    Ravn, Ib

    2015-01-01

    , attitudes or subsequent behavior. 3. Underlying this meeting format is the information transmission model. It assumes that information sent equals information received. But the mind filters and discards information not perceived as immediately relevant or usable. This is the fate of most presentations. 4....... A more viable model of human communication has people sharing knowledge that leads to action. To generate such actionable knowledge, meetings must enable participants to be active, to interpret and discuss the presentations, to be autonomously motivated, to engage in social relations with peers...

  1. Reduced cellular redox status induces 4-hydroxynonenal-mediated caspase 3 activation leading to erythrocyte death during chronic arsenic exposure in rats.

    Science.gov (United States)

    Biswas, Debabrata; Sen, Gargi; Biswas, Tuli

    2010-05-01

    Chronic exposure to arsenic in rats led to gradual accumulation of the toxicant in erythrocytes causing oxidative stress in these cells. 4-Hydroxynonenal (4-HNE), a major aldehyde product of lipid peroxidation, contributed significantly to the cytopathological events observed during oxidative stress in the erythrocytes of exposed rats. 4-HNE triggered death signal cascade that was initiated with the formation of HNE-protein adducts in cytosol. HNE-protein adduct formation resulted in depletion of cytosolic antioxidants followed by increased generation of ROS. Results showed accumulation of hydrogen peroxide (H(2)O(2)) from the early stages of arsenic exposure, while superoxide (O(2)(*-)) and hydroxyl radical ((*)OH) also contributed to the oxidative stress during longer period of exposure. Suppression of antioxidant system coupled with increased generation of ROS eventually led to activation of caspase 3 during arsenic exposure. Attenuation of HNE-mediated activation of caspase 3 in presence of N-acetylcysteine (NAC) indicated the involvement of GSH in the process. Prevention of HNE-mediated degradation of membrane proteins in presence of Z-DEVD-FMK identified caspase 3 as the principal mediator of HNE-induced cellular damage during arsenic exposure. Degradation of band 3 followed by its aggregation on the red cell surface promoted immunologic recognition of redistributed band 3 by autologous IgG with subsequent attachment of C3b. Finally, the formation of C3b-IgG-band 3 immune complex accelerated the elimination of affected cells from circulation and led to the decline of erythrocyte life span during chronic arsenic toxicity. Copyright 2008 Elsevier Inc. All rights reserved.

  2. 78 FR 14415 - Agency Information Collection Activities; Comment Request of the Proposed Changes to the Report...

    Science.gov (United States)

    2013-03-05

    ... intelligence or counter-intelligence activities to protect against international terrorism, and to implement... delegated to the Director of FinCEN. \\1\\ Language expanding the scope of the Bank Secrecy Act to intelligence or counter-intelligence activities to protect against international terrorism was added by Section...

  3. 75 FR 39247 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-07-08

    ..., Primary Lead Smelters, Primary Aluminum Reduction Plants, and Ferroalloy Production Facilities, (Renewal..., Primary Lead Smelters, and Ferroally Production Facilities (Renewal) ICR Numbers: EPA ICR Number 1604.09... lead smelters, primary aluminum reduction plants, and ferroalloy production facilities. Estimated...

  4. 75 FR 54336 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-09-07

    ...: Chromium Compounds, Flexible Polyurethane Foam Production and Fabrication, Lead Acid Battery Manufacturing..., Chemical Manufacturing: Chromium Compounds, Flexible Polyurethane Foam Production and Fabrication, Lead... Polyurethane Foam Production and Fabrication, Lead Acid Battery Manufacturing, and Wood Preserving were...

  5. Variable training does not lead to better motor learning compared to repetitive training in children with and without DCD when exposed to active video games.

    Science.gov (United States)

    Bonney, Emmanuel; Jelsma, Dorothee; Ferguson, Gillian; Smits-Engelsman, Bouwien

    2017-03-01

    Little is known about the influence of practice schedules on motor learning and skills transfer in children with and without developmental coordination disorder (DCD). Understanding how practice schedules affect motor learning is necessary for motor skills development and rehabilitation. The study investigated whether active video games (exergames) training delivered under variable practice led to better learning and transfer than repetitive practice. 111 children aged 6-10 years (M=8.0, SD=1.0) with no active exergaming experience were randomized to receive exergames training delivered under variable (Variable Game Group (VGG), n=56) or repetitive practice schedule (Repetitive Game Group (RGG), n=55). Half the participants were identified as DCD using the DSM-5 criteria, while the rest were typically developing (TD), age-matched children. Both groups participated in two 20min sessions per week for 5 weeks. Both participant groups (TD and DCD) improved equally well on game performance. There was no significant difference in positive transfer to balance tasks between practice schedules (Repetitive and Variable) and participant groups (TD and DCD). Children with and without DCD learn balance skills quite well when exposed to exergames. Gains in learning and transfer are similar regardless of the form of practice schedule employed. This is the first paper to compare the effect of practice schedules on learning in children with DCD and those with typical development. No differences in motor learning were found between repetitive and variable practice schedules. When children with and without DCD spend the same amount of time on exergames, they do not show any differences in acquisition of motor skills. Transfer of motor skills is similar in children with and without DCD regardless of differences in practice schedules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The Matrix Element Method at Next-to-Leading Order

    OpenAIRE

    Campbell, John M.; Giele, Walter T.; Williams, Ciaran

    2012-01-01

    This paper presents an extension of the matrix element method to next-to-leading order in perturbation theory. To accomplish this we have developed a method to calculate next-to-leading order weights on an event-by-event basis. This allows for the definition of next-to-leading order likelihoods in exactly the same fashion as at leading order, thus extending the matrix element method to next-to-leading order. A welcome by-product of the method is the straightforward and efficient generation of...

  7. 77 FR 37904 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-06-25

    ... part 63, subpart WWWW. Owners or operators of the affected facilities must submit initial notification... office. This information is being collected to assure compliance with 40 CFR part 63, subpart WWWW, as...

  8. 75 FR 6022 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-02-05

    ... comments may be submitted on or before March 8, 2010. ADDRESSES: Submit your comments, referencing Docket... sufficient information is available to make a thorough analysis of anticipated impacts. These minimum...

  9. 75 FR 60772 - Agency Information Collection Activities: Transportation Entry and Manifest of Goods Subject to...

    Science.gov (United States)

    2010-10-01

    ... proposed collection of information, including the validity of the methodology and assumptions used; (3....gov/xp/cgov/toolbox/forms/ . Current Actions: This submission is being made to extend the expiration...

  10. 78 FR 43238 - Agency Information Collection Activities: Submission to OMB for Reinstatement, Without Change, of...

    Science.gov (United States)

    2013-07-19

    ... a Previously Approved Collection; Comment Request AGENCY: National Credit Union Administration (NCUA... comments from the public. The information collection applies to credit unions that engage in member... From the Federal Register Online via the Government Publishing Office NATIONAL CREDIT UNION...

  11. 77 FR 38627 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-06-28

    .../ operators of construction and demolition waste landfills that receive Conditionally Exempt Small Quantity... to be construction and demolition landfills that receive CESQG waste from off-site generators. EPA has reviewed Biocycle trade magazine and has concluded that the number of Construction and Demolition...

  12. 75 FR 10791 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-03-09

    ... Request; Questionnaire for Steam Electric Power Generating Effluent Guidelines (New); EPA ICR No. 2368.01...), EPA sought comments on this ICR pursuant to 5 CFR 1320.8(d). EPA received comments from electric power... the docket that are available electronically. Once in the system, select ``docket search,'' then key...

  13. 78 FR 65622 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-11-01

    ... development activities intended to improve instruction for students with limited English proficiency and... AGENCY: Office of English Language Acquisition (OELA), Department of Education (ED). ACTION: Notice...

  14. Learning to Succeed in a Flat World: Information and Communication Technologies for a New Generation of Business Students

    Science.gov (United States)

    Ramirez, Alex; Hine, Michael; J.; Ji, Shaobo; Ulbrich, Frank; Riordan, Rob

    2009-01-01

    This article investigates the relationship of learning and its infrastructure using Web 2.0 technologies to facilitate the acquisition of skills needed to succeed in a global economy. We explore the learning phenomenon as a way to bring forward a process of continuous improvement supported by social software. We use a commonly accepted definition…

  15. All Roads Lead To Rome

    DEFF Research Database (Denmark)

    Ottosen, Thorsten Jørgen; Vomlel, Jiri

    2010-01-01

    To perform ecient inference in Bayesian networks, the network graph needs to be triangu- lated. The quality of this triangulation largely determines the efficiency of the subsequent inference, but the triangulation problem is unfortunately NP-hard. It is common for ex- isting methods to use the t...

  16. Not Too Young to Lead

    Science.gov (United States)

    Pucella, Tanya Judd

    2014-01-01

    "Educational Leadership" is a term used to describe the work of principals and administrators. The high-stakes testing environment that has been feeding the culture of accountability in our schools has led principals to increasingly turn to a more distributed leadership model that includes their teachers, thereby expanding the concept of…

  17. Rapid Microsatellite Marker Development Using Next Generation Pyrosequencing to Inform Invasive Burmese Python—Python molurus bivittatus—Management

    OpenAIRE

    Hart, Kristen M; Hunter, Margaret E.

    2013-01-01

    Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus, is one of the most notable invasive species in the US, due to the threat it poses to imperiled species and the Greater Everglades ecosyste...

  18. Use of an active fixation lead and a subpectoral pacemaker pocket may not avoid Twiddler′s syndrome

    Directory of Open Access Journals (Sweden)

    Floris E A Udink ten Cate

    2012-01-01

    Full Text Available Manipulation of a pacemaker with consequent malfunction of the device has been called Twiddler′s syndrome. Use of active-fixation leads and subpectoral pacemaker pockets has been considered to help in avoiding this problem. We describe a child in whom twiddling was not prevented despite implantation of a lumenless atrial lead and insertion of the pacemaker generator in a subpectoral pocket.

  19. Mass Lead Intoxication from Informal Used Lead-Acid Battery Recycling in Dakar, Senegal

    National Research Council Canada - National Science Library

    Pascal Haefliger; Monique Mathieu-Nolf; Stephanie Lociciro; Cheikh Ndiaye; Malang Coly; Amadou Diouf; Absa Lam Faye; Aminata Sow; Joanna Tempowski; Jenny Pronczuk; Antonio Pedro Filipe Junior; Roberto Bertollini; Maria Neira

    2009-01-01

    Background and Objectives: Between November 2007 and March 2008, 18 children died from a rapidly progressive central nervous system disease of unexplained origin in a community involved in the recycling of used lead-acid batteries (ULAB...

  20. Twitter as a Teaching Practice to Enhance Active and Informal Learning in Higher Education: The Case of Sustainable Tweets

    Science.gov (United States)

    Kassens-Noor, Eva

    2012-01-01

    With the rise of Web 2.0, a multitude of new possibilities on how to use these online technologies for active learning has intrigued researchers. While most instructors have used Twitter for in-class discussions, this study explores the teaching practice of Twitter as an active, informal, outside-of-class learning tool. Through a comparative…

  1. Learning to lead at Toyota.

    Science.gov (United States)

    Spear, Steven J

    2004-05-01

    Many companies have tried to copy Toyota's famous production system--but without success. Why? Part of the reason, says the author, is that imitators fail to recognize the underlying principles of the Toyota Production System (TPS), focusing instead on specific tools and practices. This article tells the other part of the story. Building on a previous HBR article, "Decoding the DNA of the Toyota Production System," Spear explains how Toyota inculcates managers with TPS principles. He describes the training of a star recruit--a talented young American destined for a high-level position at one of Toyota's U.S. plants. Rich in detail, the story offers four basic lessons for any company wishing to train its managers to apply Toyota's system: There's no substitute for direct observation. Toyota employees are encouraged to observe failures as they occur--for example, by sitting next to a machine on the assembly line and waiting and watching for any problems. Proposed changes should always be structured as experiments. Employees embed explicit and testable assumptions in the analysis of their work. That allows them to examine the gaps between predicted and actual results. Workers and managers should experiment as frequently as possible. The company teaches employees at all levels to achieve continuous improvement through quick, simple experiments rather than through lengthy, complex ones. Managers should coach, not fix. Toyota managers act as enablers, directing employees but not telling them where to find opportunities for improvements. Rather than undergo a brief period of cursory walk-throughs, orientations, and introductions as incoming fast-track executives at most companies might, the executive in this story learned TPS the long, hard way--by practicing it, which is how Toyota trains any new employee, regardless of rank or function.

  2. Comprehensive program and plan for federal energy education, extension, and information activities: Fiscal Year 1981. Fifth report to congress

    Energy Technology Data Exchange (ETDEWEB)

    1981-12-01

    The activities conducted solely in Fiscal Year (FY) 1981 in the areas of Federal energy education, extension service, and information dissemination are reported. The broad purpose of the FY 1981 activities addressed has been to inform governmental and private sectors about the methods and technologies to conserve energy and to utilize renewable energy sources. With the increase in awareness on the part of energy users and decisionmakers, as well as additional information sources available from the private sector, the emphasis of the various Federal energy information activities is being focused on reporting results of Federal programs. The course of activities related to conservation and renewable energy information has been one of consolidation, both in terms of programmatic substance and methods. The practical impetus has been the redirection of Federal progrms and related budgetary revisions for FY 1981 and FY 1982. Further, products conveying information on conservation and renewable energy technologies have been examined extensively, pursuant to the Administration's directive in April 1981 on elimination of wasteful spending on periodicals, audiovisuals and similar materials. Efforts in coordination of conservation and renewable energy information activities of the Department of Energy (DOE) as well as other Federal agencies have adjusted to timetables for review and redirection of programs initially planned for FY 1981. Mechanisms to coordinate existing Federal energy information activities employed in previous fiscal years were continued in FY 1981 to the extent applicable under current Administration policy and the above-noted circumstances of redirection. Coordinating actions requiring convening of groups were held in abeyance pending resolution of programmatic issues.

  3. When envy leads to schadenfreude

    NARCIS (Netherlands)

    van de Ven, N.; Hoogland, C.E.; Smith, R.H.; van Dijk, W.W.; Breugelmans, S.M.; Zeelenberg, M.

    2015-01-01

    Previous research has yielded inconsistent findings concerning the relationship between envy and schadenfreude. Three studies examined whether the distinction between benign and malicious envy can resolve this inconsistency. We found that malicious envy is related to schadenfreude, while benign envy

  4. Deployment Support Leading to Implementation

    Energy Technology Data Exchange (ETDEWEB)

    Cook, E E

    1997-10-01

    The following paragraphs summarize the progress of each research project funded under the WVU Cooperative Agreement during the third quarter of 1997 (July - September 1997). The projects are arranged according to their 1997 WVU task number. WVU Focus Area 1.0: Subsurface Contaminants, Containment and Remediation Task No. 1.1: Project discontinued. Task No. 1.2: Development of Standard Test Protocols and Barrier Design Models for Desiccation Barriers (K. Amininan & S. Ameri): A number of experiments were preformed this period to evaluate the ability of the dried sand-packs to act as a barrier to liquids. Water infiltration tests were done with a constant head, dispersing 80 ml of water, and by adding water in small increments. Results indicate that when the water is spilled over the sand-pack, it has the tendency to channel through the sand-pack, significantly reducing the capacity of the dried zone to retain liquid contaminants. This appears to be largely influenced by particle size. As the particle size is reduced, the capillary forces spread the water and prevent/delay channels from forming. The measured permeability values were in agreement with those measured with air. The water retention capacity and capillary rise were largely influenced by time and showed no sensitivity to channeling. The water retention capacity tests suggest the sand-packs can retain more water than the expected. Two sets of water infiltration and drying experiments were designed to evaluate the CAB's ability to prevent spills from spreading. Ten ml of water was injected every 20 minutes and 80 ml of water was added at one time. When injected slowly, results showed the drying process to be similar to the original drying process. The second set indicted the drying process follows a slowly declining drying with no break through. Results also suggested that air flow through the sand-pack can remove water infiltration. The air flow appeared to prevent any water channeling and thus should

  5. Reflective Insights from Today's Fire Service Leaders: A Narrative Inquiry to Inform the Next Generation's Leadership Development

    Science.gov (United States)

    Buttenschon, Marianne

    2016-01-01

    The success of any organization is dependent, in part, on the quality of its leaders. The fire department is no exception. In fact, one could argue that effective leadership in the fire department has become more critical than ever in today's world. This critical need for an effective fire department dates back to the unprecedented terrorist…

  6. Emergent Understandings: Multilingual Fourth Grade Students Generating Close Readings and Multimodal Responses to Global and Informational Texts

    Science.gov (United States)

    Hasty, Michelle Medlin; Fain, Jeanne Gilliam

    2014-01-01

    In this paper, the authors present findings from a yearlong ethnographic research study that examines the development of critical literacy within two urban fourth grade classrooms in Tennessee. This study examines how young second language learners in English-dominant classrooms learn to read critically, write, and construct multimodal…

  7. All roads lead to Rome

    DEFF Research Database (Denmark)

    Ottosen, Thorsten Jørgen; Vomlel, Jiri

    2012-01-01

    size triangulations. The search methods are made faster by efficient dynamic maintenance of the cliques of a graph. This problem was investigated by Stix, and in this paper we derive a new simple method based on the Bron-Kerbosch algorithm that compares favourably to Stix’ approach. The new approach...

  8. Forest development leading to disturbances

    Science.gov (United States)

    Clinton E. Carlson; Stephen F. Arno; Jimmie Chew; Catherine A. Stewart

    1995-01-01

    Natural disturbance in western U.S.A. forest ecosystems is related to forest succession, growth, and structural development. Natural disturbance may be biotic (insects and diseases) or abiotic (fire, wind, avalanche, etc.). Natural disturbances are more appropriately thought of as natural processes; disturbance is a social connotation implicating economic loss. Forest...

  9. Met117 oxidation leads to enhanced flexibility of cardiovascular biomarker- lipoprotein- associated phospholipase A2 and reduced substrate binding affinity with platelet-activating factor.

    Science.gov (United States)

    Gurung, Arun Bahadur; Bhattacharjee, Atanu

    2018-02-07

    Human Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an important biomarker for cardiovascular diseases and a therapeutically important drug target against Atherosclerosis. It has the ability to hydrolyze various oxidized low density lipoproteins (LDL) and generates potent pro-inflammatory signaling molecules. Both physiological and non-physiological oxidants have been reported to inhibit Lp-PLA2 activity. The mechanism of the enzyme inhibition due to oxidation of surface exposed Met117 at the structural level is not clearly understood. In the present work, molecular dynamics (MD) simulation and Essential dynamics (ED) has been used in tandem with molecular docking approach to understand the structural alteration in Lp-PLA2 upon Met117 oxidation. Further, the binding of substrate, Platelet-activating factor (PAF) with the wild type and oxidized form have also been investigated. Our results showed that Met117 oxidation caused enhanced flexibility and decreased compactness in oxidized state. PAF binding interaction with oxidized protein was mediated only through hydrophobic interactions. MD simulation studies revealed that the oxidized protein failed to firmly bind PAF. Our present findings will help understand the mechanism of Lp-PLA2 inhibition under oxidative stress. Copyright © 2018. Published by Elsevier B.V.

  10. A three-dimensional modelling study of the processes leading to mid latitude nitric oxide increases in the lower thermosphere following periods of high geomagnetic activity

    Science.gov (United States)

    Dobbin, A. L.; Aylward, A. D.

    2008-11-01

    The processes leading to enhancements in mid latitude nitric oxide (NO) densities following geomagnetic storms have been investigated using the University College London (UCL) Coupled Middle Atmosphere and Thermosphere (CMAT) general circulation model. A comparison of calculated storm time and quiet time NO densities at 110 km altitude reveals the presence of aurorally produced NO at both high and mid latitudes for several days after subsidence of activity. At 150 km, the NO enhancements are shorter lived and remain for up to approximately 2 days after the storm. By separating the contribution of chemical production and loss, horizontal and vertical advection, and molecular and eddy diffusion in the calculation of NO densities, we show that at 150 km altitude, horizontal transport must be taken into consideration if post-storm mid latitude enhancements are to be reproduced. Chemical production of NO at high latitudes continues for up to 2 days after subsidence of a storm at altitudes of around 150 km. We show that equatorward winds at this altitude are sufficiently strong to transport the aurorally produced NO to mid latitudes. Vertical diffusion transports NO from altitudes of 150 km and above, to lower altitudes where it is longer lived. At 110 km altitude, chemical, diffusive and advective terms must all be included in the calculation of NO density in order to simulate realistic mid latitude enhancements. We propose that it is the combined effects of increased chemical production, downward diffusion from altitudes of 150 km and above, and transport by winds that lead to increases in mid latitude NO density at altitudes of around 110 km. This is the first detailed study of the causes of post-storm mid latitude NO enhancements to use a three-dimensional general circulation model.

  11. Carrying-over effects of GVBD blocking on post-blocking meiotic progression of oocytes: species difference and the signaling pathway leading to MPF activation.

    Directory of Open Access Journals (Sweden)

    Guang-Zhong Jiao

    Full Text Available Efforts to improve the quality of in vitro matured oocytes by blocking germinal vesicle breakdown (GVBD and allowing more time for ooplasmic maturation have achieved little due to a lack of knowledge on the molecular events during GVBD blocking. Such knowledge is also important for studies aimed at regulating gene expression in maturing oocytes prior to GVBD. We studied species difference and signaling pathways leading to the carrying-over effect of GVBD blocking on post-blocking meiotic progression (PBMP. Overall, GVBD-blocking with roscovitine decelerated PBMP of mouse oocytes but accelerated that of pig oocytes. During blocking culture, whereas cyclin B of pig oocytes increased continuously, that of mouse oocytes declined first and then increased slowly. In both species, (a whereas active CDC2A showed a dynamics similar to cyclin B, inactive CDC2A decreased continuously; (b when oocytes were blocked in blocking medium containing cycloheximide, PBMP was decelerated significantly while cyclin B and active CDC2A decreasing to the lowest level; (c whereas sodium vanadate in blocking medium reduced PBMP, epidermal growth factor (EGF in blocking medium accelerated PBMP significantly with no effect on cyclin B levels. In conclusion, the EGF signaling cascade accelerated PBMP by promoting the pre-MPF (M-phase-promoting factor to MPF conversion during GVBD blocking with roscovitine. The significant difference in PBMP observed between mouse and pig oocytes was caused by species difference in cyclin B dynamics during blocking culture as no species difference was observed in either pre-MPF to MPF conversion or the EGF signaling activity.

  12. When envy leads to schadenfreude.

    Science.gov (United States)

    van de Ven, Niels; Hoogland, Charles E; Smith, Richard H; van Dijk, Wilco W; Breugelmans, Seger M; Zeelenberg, Marcel

    2015-01-01

    Previous research has yielded inconsistent findings concerning the relationship between envy and schadenfreude. Three studies examined whether the distinction between benign and malicious envy can resolve this inconsistency. We found that malicious envy is related to schadenfreude, while benign envy is not. This result held both in the Netherlands where benign and malicious envy are indicated by separate words (Study 1: Sample A, N = 139; Sample B, N = 150), and in the USA where a single word is used to denote both types (Study 2, N = 180; Study 3, N = 349). Moreover, the effect of malicious envy on schadenfreude was independent of other antecedents of schadenfreude (such as feelings of inferiority, disliking the target person, anger, and perceived deservedness). These findings improve our understanding of the antecedents of schadenfreude and help reconcile seemingly contradictory findings on the relationship between envy and schadenfreude.

  13. A Public Health Approach to Addressing Lead

    Science.gov (United States)

    Describes EPA’s achievements in reducing childhood lead exposures and emphasizes the need to continue actions to further reduce lead exposures, especially in those communities where exposures remain high.

  14. Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone

    National Research Council Canada - National Science Library

    Italia, Jagdishbhai L; Sharp, Andrew; Carter, Katharine C; Warn, Peter; Kumar, M N V Ravi

    2011-01-01

    ...%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation...

  15. Lead

    Science.gov (United States)

    ... is serious about making sure companies that break the law are held accountable In the past year, EPA ... the health effects of lead in drinking water The law mandates no-lead products for drinking water after ...

  16. 78 FR 21380 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-04-10

    ... goals of Corps Community Day encompass the following: increase awareness of the NHSC to potential... will also be approximately 5 fields to populate following the event to measure satisfaction. Both the... information requested. This includes the time needed to review instructions, to develop, acquire, install and...

  17. 78 FR 47424 - Agency Information Collection Activities: Submission to OMB for Reinstatement, With Change, of a...

    Science.gov (United States)

    2013-08-05

    ... From the Federal Register Online via the Government Publishing Office NATIONAL CREDIT UNION... activity, in advertisements, and upon a member or potential member's request. The disclosures are for the... is close to renewal, on periodic statements of account activity, in advertisements, and upon a member...

  18. 78 FR 59378 - Agency Information Collection Activities: Submission to OMB for Reinstatement, With Change, of a...

    Science.gov (United States)

    2013-09-26

    ... From the Federal Register Online via the Government Publishing Office NATIONAL CREDIT UNION... activity, in advertisements, and upon a member or potential member's request. The disclosures are for the... close to renewal, on periodic statements of ] account activity, in advertisements, and upon a member or...

  19. Sorption of Lead (II Ions on Activated Coconut Husk

    Directory of Open Access Journals (Sweden)

    Amin Jahangard

    2016-10-01

    Full Text Available Background: In recent years, various toxic chemicals/compounds have been widely detected at dangerous levels in drinking water in many parts of the world posing a variety of serious health risks to human beings. One of these toxic chemicals is lead, so this paper aimed to evaluate of efficiency coconut husk as cheap adsorbent for removal lead under different conditions. Methods: In the spring of 2015, batch studies were performed in laboratory (Branch of Hamadan, Islamic Azad University, to evaluate the influences of various experimental parameters like pH, initial concentration, adsorbent dosage, contact time and the effect of temperature on the adsorption capacity of coconut husk for removal lead from aqueous solution. Results: Optimum conditions for Pb (II removal were pH 6, adsorbent dosage 1g/100ml of solution and equilibrium time 120 min. The adsorption isotherm was also affected by temperature since the adsorption capacity was increased by raising the temperature from 25 to 45 °C. The equilibrium adsorption isotherm was better described by Freuindlich adsorption isotherm model. Conclusion: It is evident from the literature survey that coconut-based biosorbents have shown good potential for the removal of various aquatic pollutants. Coconut husk-based activated carbon can be a promising adsorbent for removal of Pb from aqueous solutions.

  20. Computational investigation of the flow field contribution to improve electricity generation in granular activated carbon-assisted microbial fuel cells

    Science.gov (United States)

    Zhao, Lei; Li, Jian; Battaglia, Francine; He, Zhen

    2016-11-01

    Microbial fuel cells (MFCs) offer an alternative approach to treat wastewater with less energy input and direct electricity generation. To optimize MFC anodic performance, adding granular activated carbon (GAC) has been proved to be an effective way, most likely due to the enlarged electrode surface for biomass attachment and improved mixing of the flow field. The impact of a flow field on the current enhancement within a porous anode medium (e.g., GAC) has not been well understood before, and thus is investigated in this study by using mathematical modeling of the multi-order Butler-Volmer equation with computational fluid dynamics (CFD) techniques. By comparing three different CFD cases (without GAC, with GAC as a nonreactive porous medium, and with GAC as a reactive porous medium), it is demonstrated that adding GAC contributes to a uniform flow field and a total current enhancement of 17%, a factor that cannot be neglected in MFC design. However, in an actual MFC operation, this percentage could be even higher because of the microbial competition and energy loss issues within a porous medium. The results of the present study are expected to help with formulating strategies to optimize MFC with a better flow pattern design.